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| 2. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 4. |
- Bohge, Mathias, et al.
(författare)
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A New Optimization Model for Dynamic Power and Sub-Carrier Allocations in Packet-Centric OFDMA Cells
- 2007
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Ingår i: Frequenz. - : FACHVERLAG SCHIELE SCHON. - 0016-1136 .- 2191-6349. ; 61:1-2, s. 35-38
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that applying dynamic resource allocation to down-link transmissions of OFDMAsystems provides a significant performance increase, by taking advantage of diversity effects. In order toquantify the maximum possible gain achievable by applying dynamic mechanisms, several optimizationproblems have been suggested for studying a dynamic system's optimal behaviour. However, so far theseoptimization approaches do not take sophisticated system requirements into account, as there are differentpacket-arrival processes, buffering constraints, scheduling policies, as well as QoS requirements per serviceclass. In this paper we present a new optimization model that is based on a packet-centric system view andincludes the system requirements mentioned above. We compare the performance results of the conventionaland the new approach and study the impact of dynamic power allocation in both cases.
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| 5. |
- Bohge, Mathias, et al.
(författare)
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Dynamic Resource Allocation in OFDM Systems : An Overview of Cross-Layer Optimization Principles and Techniques
- 2007
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Ingår i: IEEE Network. - : IEEE Communications Society. - 0890-8044 .- 1558-156X. ; 21:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a lot of research effort has been spent on cross-layer system design. It has been shown that cross-layer mechanisms (i.e., policies) potentially provide significant performance gains for various systems. In this article we review several aspects of cross-layer system optimization regarding wireless OFDM systems. We discuss basic optimization models and present selected heuristic approaches realizing cross-layer policies by means of dynamic resource allocation. Two specific areas are treated separately: models and dynamic approaches for single transmitter/receiver pairs (i.e., a point-to-point communication scenario) as well as models and approaches for point-to-multipoint communication scenarios (e.g., the downlink of a wireless cell). This article provides basic knowledge in order to investigate future OFDM cross-layer-optimization issues.
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| 6. |
- C Stummann, Tina C, et al.
(författare)
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Report and Recommendations of the Workshop of the European Centre for the Validation of Alternative Methods for Drug-Induced Cardiotoxicity
- 2009
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Ingår i: CARDIOVASCULAR TOXICOLOGY. - : Springer Science and Business Media LLC. - 1530-7905 .- 1559-0259. ; 9:3, s. 107-125
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Cardiotoxicity is among the leading reasons for drug attrition and is therefore a core subject in non-clinical and clinical safety testing of new drugs. European Centre for the Validation of Alternative Methods held in March 2008 a workshop on "Alternative Methods for Drug-induced Cardiotoxicity" in order to promote acceptance of alternative methods reducing, refining or replacing the use of laboratory animals in this field. This review reports the outcome of the workshop. The participants identified the major clinical manifestations, which are sensitive to conventional drugs, to be arrhythmias, contractility toxicity, ischaemia toxicity, secondary cardiotoxicity and valve toxicity. They gave an overview of the current use of alternative tests in cardiac safety assessments. Moreover, they elaborated on new cardiotoxicological endpoints for which alternative tests can have an impact and provided recommendations on how to cover them.
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| 7. |
- Gardner, James M., 1982-, et al.
(författare)
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Evidence for Iodine Atoms as Intermediates in the Dye Sensitized Formation of I-ˆ’I Bonds
- 2008
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 130:51, s. 17252-17253
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Tidskriftsartikel (refereegranskat)abstract
- Visible light excitation of [Ru(bpz)2(deeb)](PF6)2, where bpz is 2,2?-bipyrazine and deeb is 4,4?-(CO2Et)2-2,2?-bipyridine, in acetonitrile solutions with iodide is shown to initiate excited-state electron transfer reactions that yield iodine atoms. The iodine atoms subsequently react with iodide to form the I?I bond in I2??. The resultant Ru(bpz?)(bpz)(deeb)+, I2?? stores ?1.64 eV of free energy and returns cleanly to ground-state products with kcr = (2.1 ± 0.3) ? 1010 M?1 s?1.
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| 8. |
- Gardner, James M., 1982-, et al.
(författare)
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Visible Light Generation of Iodine Atoms and I-ˆ’I Bonds : Sensitized I-ˆ’ Oxidation and I3-ˆ’ Photodissociation
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:44, s. 16206-16214
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Tidskriftsartikel (refereegranskat)abstract
- Direct 355 or 532 nm light excitation of TBAI3, where TBA is tetrabutyl ammonium, in CH3CN at room temperature yields an iodine atom, I?, and an iodine radical anion, I2??. In the presence of excess iodide, the iodine atom reacts quantitatively to yield a second equivalent of I2?? with a rate constant of k = 2.5 ± 0.4 ? 1010 M?1 s?1. The I2?? intermediates are unstable with respect to disproportionation and yield initial reactants, k = 3.3 ± 0.1 ? 109 M?1 s?1. The coordination compound Ru(bpz)2(deeb)(PF6)2, where bpz is 2,2?-bipyrazine and deeb is 4,4?-(C2H5CO2)2-2,2?-bipyridine, was prepared and characterized for mechanistic studies of iodide photo-oxidation in acetonitrile at room temperature. Ru(bpz)2(deeb)2+ displayed a broad metal-to-ligand charge transfer (MLCT) absorption band at 450 nm with ε = 1.7 ? 104 M?1 cm?1. Visible light excitation resulted in photoluminescence with a corrected maximum at 620 nm, a quantum yield ? = 0.14, and an excited state lifetime τ = 1.75 ?s from which kr = 8.36 ? 104 s?1 and knr = 5.01 ? 105 s?1 were abstracted. Arrhenius analysis of the temperature dependent excited state lifetime revealed an activation energy of ?2500 cm?1 and a pre-exponential factor of 1010 s?1, assigned to activated surface crossing to a ligand field or MLCT excited state. Steady state light excitation of Ru(bpz)2(deeb)2+ in a 20 mM TBAI acetonitrile solution resulted in ligand loss photochemistry with a quantum yield of 5 ? 10?5. The MLCT excited state was dynamically quenched by iodide with Ksv = 1.1 ? 105 M?1 and kq = 6.6 ± 0.3 ? 1010 M?1 s?1, a value consistent with diffusion-limited electron transfer. Excited state hole transfer to iodide was quantitative but the product yield was low due to poor cage escape yields, ?CE = 0.042 ± 0.001. Nanosecond transient absorption was used to quantify the appearance of two photoproducts [Ru(bpz?)(bpz)(deeb)]+ and I2??. The coincidence of the rate constants for [Ru(bpz?)(bpz)(deeb)]+ formation and for excited state decay indicated reductive quenching by iodide. The rate constant for the appearance of I2?? was about a factor of 3 slower than excited state decay, k = 2.4 ± 0.2 ? 1010 M?1 s?1, indicating that I2?? was not a primary photoproduct of excited state electron transfer. A mechanism was proposed where an iodine atom was the primary photoproduct that subsequently reacted with iodide, I? + I? ? I2??. Charge recombination Ru(bpz?)(bpz)(deeb)+ + I2?? ? Ru(bpz)2(deeb)2+ + 2I? was highly favored, ?Go = ?1.64 eV, and well described by a second-order equal concentration kinetic model, kcr = 2.1 ± 0.3 ? 1010 M?1 s?1.
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| 9. |
- Larsson, Andreas, et al.
(författare)
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Orientation of individual C60 molecules adsorbed on Cu(111) : Low-temperature scanning tunneling microscopy and density functional calculations
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 77:11
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Tidskriftsartikel (refereegranskat)abstract
- Density functional theory (DFT) and low-temperature scanning tunneling microscopy (STM) have been combined to examine the bonding of individual C60 molecules on Cu(111). Energy-resolved differential-conductance maps have been measured for individual C60 molecules adsorbed on a Cu(111) surface by means of low-temperature STM, which are compared to and complemented by theoretically computed spectral images. It has been found that C60 chemisorbs with a six-membered ring parallel to the surface at two different Cu(111) binding sites that constitute two exclusive hexagonal sublattices. On each sublattice, C60 is bonded in one particular rotational conformer, i.e., C60 molecules bind to the Cu(111) surface in two different azimuthal orientations differing by 60°depending on which sublattice the binding site belongs to. The binding conformation of C60 and its orientation with regard to the copper surface can be deduced by this joint experimental-theoretical approach. Six possible pairs of C60 configurations on three different Cu surface binding sites have been identified that fulfil the requirements of the two sublattices and are consistent with all experimental and theoretical data. Theory proposes that two of these configuration pairs are most likely. We have found that DFT does not get the binding energy between rotational conformers in the correct order. We also report two different C60 monolayers on Cu(111): one with alternating orientations of neighboring molecules at low temperature and the other with (4×4) structure after annealing above room temperature.
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| 10. |
- Meyer, Martin P, et al.
(författare)
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Characterization of zebrafish PSD-95 gene family members.
- 2005
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Ingår i: Journal of Neurobiology. - : Wiley. - 0022-3034 .- 1097-4695. ; 63:2, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- The PSD-95 family of membrane- associated guanylate kinases (MAGUKs) are thought to act as molecular scaffolds that regulate the assembly and function of the multiprotein signaling complex found at the postsynaptic density of excitatory synapses. Genetic analysis of PSD-95 family members in the mammalian nervous system has so far been difficult, but the zebrafish is emerging as an ideal vertebrate system for studying the role of particular genes in the developing and mature nervous system. Here we describe the cloning of the zebrafish orthologs of PSD-95, PSD-93, and two isoforms of SAP-97. Using in situ hybridization analysis we show that these zebrafish MAGUKs have overlapping but distinct patterns of expression in the developing nervous system and craniofacial skeleton. Using a pan-MAGUK antibody we show that MAGUK proteins localize to neurons within the developing hindbrain, cerebellum, visual and olfactory systems, and to skin epithelial cells. In the olfactory and visual systems MAGUK proteins are expressed strongly in synaptic regions, and the onset of expression in these areas coincides with periods of synapse formation. These data are consistent with the idea that PSD-95 family members are involved in synapse assembly and function, and provide a platform for future functional studies in vivo in a highly tractable model organism.
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