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- Jaffee, E. M., et al.
(författare)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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Ingår i: Lancet Oncology. - 1470-2045. ; 18:11
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Forskningsöversikt (refereegranskat)abstract
- We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$ 2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
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- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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- Adamson, R. E., et al.
(författare)
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In Vitro Primary Cell Culture as a Physiologically Relevant Method for Preclinical Testing of Human Oncolytic Adenovirus
- 2012
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 23:2, s. 218-230
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Tidskriftsartikel (refereegranskat)abstract
- Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.
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- Buyanova, Irina, 1960-, et al.
(författare)
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Optical study of spin injection dynamics in InGaN/GaN quantum wells with GaMnN injection layers
- 2004
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 22:6, s. 2668-2672
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Tidskriftsartikel (refereegranskat)abstract
- The spin injection dynamics of GaMnN/InGaN multiquantum well (MQW) light emitting diodes (LEDs) grown by molecular beam epitaxy were examined using picosecond-transient and circularly polarized photoluminescence (PL) measurements. Even with the presence of a room temperature ferromagnetic GaMnN spin injector, the LEDs are shown to exhibit very low efficiency of spin injection. Based on resonant optical orientation spectroscopy, the spin loss in the structures is shown to be largely due to fast spin relaxation within the InGaN MQW, which itself destroys any spin polarization generated by optical spin orientation or electrical spin injection. Typical photoluminescence decay times were 20-40 ns in both commercial GaN MQW LEDs with emission wavelengths between 420-470 nm and in the GaMnN/InGaN multi-quantum well MQW LEDs. In the wurtzite InGaN/GaN system, biaxial strain at the interfaces give rise to large piezoelectric fields directed along the growth axis. This built-in piezofield breaks the reflection symmetry of confining potential leading to the presence of a large Rashba term in the conduction band Hamiltonian which is responsible for the short spin relaxation times.
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- Chen, Weimin, 1959-, et al.
(författare)
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Efficient spin relaxation in InGaN/GaN and InGaN/GaMnN quantum wells : An obstacle to spin detection
- 2005
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:19, s. 192107-
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Tidskriftsartikel (refereegranskat)abstract
- Transient magneto-optical spectroscopy of InGaNGaN and InGaNGaMnN quantum wells reveals a spin relaxation process with a characteristic time of 50 ps. We show that the observed spin relaxation is mediated by spin flips of individual carriers rather than by direct exciton spin flips, and is proposed to occur near the bottom of the exciton band (K=0). Nearly complete thermalization between spin sublevels of the excitons, observed immediately after the pulsed photoexcitation, is attributed to even faster spin relaxation of photogenerated hot carriers/excitons accompanying momentum and energy relaxation at high K vectors. © 2005 American Institute of Physics.
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