1. |
- Göransson, Hanna, et al.
(author)
-
Quantification of normal cell fraction and copy number neutral LOH in clinical lung cancer samples using SNP array data
- 2009
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6, s. e6057-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinical tumor tissue. Since tumor tissue invariably contains genetically normal stromal cells, this may lead to a failure to detect aberrations in the tumor cells. PRINCIPAL FINDING: Using SNP array data from 44 non-small cell lung cancer samples we have developed a bioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples. The proportion of normal cells in combination with SNP array data can be used to detect and quantify copy number neutral loss-of-heterozygosity (CNNLOH) in the tumor cells both in crude tumor tissue and in samples enriched for tumor cells by laser capture microdissection. CONCLUSION: Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrent aberrations contributing to tumor development in clinical tumor samples. In addition, SNP-array based analysis of CNNLOH may become important for detection of aberrations that can be used for diagnostic and prognostic purposes.
|
|
2. |
- Staaf, Johan, et al.
(author)
-
Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays
- 2008
-
In: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906 .- 1465-6914. ; 9:9
-
Journal article (peer-reviewed)abstract
- We present a strategy for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome single nucleotide polymorphism genotyping data. Using a dilution series of a tumor cell line mixed with its paired normal cell line and data generated on Affymetrix and Illumina platforms, including paired tumor-normal samples and tumors characterized by fluorescent in situ hybridization, we demonstrate a high sensitivity and specificity of the strategy for detecting both minute and gross allelic imbalances in heterogeneous tumor samples.
|
|
3. |
- Svensson, Johan, 1964, et al.
(author)
-
Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II expression.
- 2007
-
In: The Journal of endocrinology. - 0022-0795. ; 193:3, s. 359-66
-
Journal article (peer-reviewed)abstract
- The GH/-IGF-I axis is important for kidney size and function and may also be involved in the development of renal failure. In this study, the role of liver-derived endocrine IGF-I for kidney size and function was investigated in mice with adult liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice). These mice have an 80-85% reduction of serum IGF-I level and compensatory increased GH secretion. Seven-month-old as well as 24-month-old LI-IGF-I(-/-) mice had decreased kidney weight. Glomerular filtration rate, assessed using creatinine clearance as well as creatinine clearance corrected for body weight, was unchanged. The 24-h urine excretion of sodium and potassium was increased in the LI-IGF-I(-/-) mice. In the 24-month-old mice, there was no between-group difference in kidney morphology. Microarray and real-time PCR (RT-PCR) analyses showed a high renal expression of IGF-II in the control mice, whereas in the LI-IGF-I(-/-) mice, there was a tissue-specific decrease in the renal IGF-II mRNA levels (-79%, P < 0.001 vs controls using RT-PCR). In conclusion, deficiency of circulating liver-derived IGF-I in mice results, despite an increase in GH secretion, in a global symmetrical decrease in kidney size, increased urinary sodium and potassium excretion, and a clear down regulation of renal IGF-II expression. However, the LI-IGF-I(-/-) mice did not develop kidney failure or nephrosclerosis. One may speculate that liver-derived endocrine IGF-I induces renal IGF-II expression, resulting in symmetrical renal growth.
|
|
4. |
- Alsiö, Johan, et al.
(author)
-
Impact of nandrolone decanoate on gene expression in endocrine systems related to the adverse effects of anabolic androgenic steroids
- 2009
-
In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 105:5, s. 307-314
-
Journal article (peer-reviewed)abstract
- Elite athletes, body builders and adolescents misuse anabolic-androgenic steroids (AAS) in order to increase muscle mass or to enhance physical endurance and braveness. The high doses misused are associated with numerous adverse effects. The purpose of this study was to evaluate the impact of chronic supratherapeutic AAS treatment on circulating hormones and gene expression in peripheral tissues related to such adverse effects. Quantitative real-time PCR was used to measure expression levels of in total 37 genes (including peptide hormones, cell membrane receptors, nuclear receptors, steroid synthesising enzymes and other enzymes) in the pituitary, testes, adrenals, adipose tissue, kidneys and liver of male Sprague-Dawley rats after 14-day administration of the AAS nandrolone decanoate, 3 or 15 mg/kg. Plasma glucose and levels of adrenocorticotropic hormone (ACTH), adiponectin, corticosterone, ghrelin, insulin and leptin were also measured. We found several expected effects on the hypothalamic-pituitary-gonadal axis, while the treatment also caused a number of other not previously identified changes in circulating factors and gene transcription levels such as the dose-dependent reduction of the beta(3)-adrenergic receptor in adipose tissue, reduction of both circulating and mRNA levels of adiponectin, up-regulation of both hydroxymethylglutaryl-CoA-reductase, the rate-limiting enzyme in de novo synthesis of cholesterol, and the receptor for ACTH in the adrenals. The results provide evidence for wide ranging effects of AAS on the hypothalamic-pituitary-adrenal axis, adipose tissue and substrates of the renal control of blood pressure.
|
|
5. |
- Andersson, Malte, 1941, et al.
(author)
-
Predator perches: a visual search perspective
- 2009
-
In: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 23, s. 373-379
-
Journal article (peer-reviewed)abstract
- 1. Predators hunting by sight often search for prey from elevated perches or hovering positions above the prey habitat. Theory suggests that prey visibility depends strongly on predator perch height and distance, but their quantitative effects have not been experimentally tested in natural habitats. 2. We estimate for the first time how prey visibility depends on predator perch height, distance and vegetation height in an open natural habitat, based on visibility measurements of two targets: a mounted bird and a graduated plate, from five perch heights (0·2–8 m) and six distances (5–120 m). 3. For both targets, their proportion visible increases strongly with observer perch height and proximity. From the lowest perch, visibility of the target bird declines to < 5% beyond 20 m distance, but 40% of it remains visible from the highest perch even at 120 m. 4. Models of predator search suggest that hunting success and predation rate depend strongly on the prey detection rate, which is expected to decline with distance r approximately as r−d. However, d, the distance decay parameter, has not previously been empirically estimated in natural predator habitats. For distance – prey visibility relationships similar to those observed here, we find a realistic estimate of d to be 2·1–2·4. 5. The results demonstrate the crucial role of relative perch and vegetation height for prey visibility, which is of relevance for habitat management. The strong increase of prey visibility with predator search height suggests that removal of predator perches can improve the survival of endangered prey populations in open habitats. Conversely, perch preservation or addition can improve habitat suitability for some predator species where perches are rare or lacking.
|
|
6. |
- Chacinski, Marek, et al.
(author)
-
High-speed direct Modulation of widely tunable MG-Y laser
- 2005
-
In: IEEE Photonics Technology Letters. - 1041-1135 .- 1941-0174. ; 17:6, s. 1157-1159
-
Journal article (peer-reviewed)abstract
- The dynamic performance of the modulated-grating Y-branch laser is presented. In order to reach over 40-nm tuning range, the devices utilize an additive Vernier effect and relative tuning of two reflecting gratings. The device shows high (> 13 dBrn ex-facet) and uniform (< 1.2-dB variation) steady state output power over the tuning range, and sidemode suppression ratio > d40 dB. The laser behavior under small- and large-signal operation conditions is investigated. The laser exhibits a resonance frequency of 7.4-8.8 GHz at 80-mA bias. A 10-Gb/s eye diagram measurement showed, high extinction ratio and signal-to-noise ratio.
|
|
7. |
|
|
8. |
- Chevul, Stefan, et al.
(author)
-
Measurements of Application-Perceived Throughput in DAB, GPRS, UMTS and WLAN Environments
- 2005
-
Conference paper (peer-reviewed)abstract
- Communication services are expected to deliver the desired information in a timely manner without challenging the user’s patience. The corresponding offers by networks are reflected in user- or applications-perceived throughput, which is measured end-to-end for different mobile and wireless networks, namely Digital Audio Broadcast (DAB), General Packet Radio Service (GPRS), Universal Mobile Telecommunication Systems (UMTS), and Wireless Local Area Networks (WLAN). The measurements are based on passive monitoring of throughput statistics for active test traffic and reveal amongst others different kinds of changes of traffic burstiness induced by mobile up- and downlinks and by buffering, respectively. The results will be used for seamless communication, i.e. automatic network selection within the project PIITSA (Personal Information for Intelligent Transport Systems through Seamless communications and Autonomous decisions) aiming at maintaining user-perceived performance and security at the desired levels while keeping communication cost as small as possible.
|
|
9. |
- Enoksson, Staffan, et al.
(author)
-
Marked Re-Utilization of Free Fatty Acids During Activated Lipolysis in Human Skeletal Muscle.
- 2005
-
In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:2, s. 1189-1195
-
Journal article (peer-reviewed)abstract
- Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P < 0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.
|
|
10. |
- Fiedler, Markus, et al.
(author)
-
Generic communication requirements of its-related mobile services as basis for seamless communications.
- 2005
-
Conference paper (peer-reviewed)abstract
- In order to meet user expectations and to be of efficient help for people using or implementing Intelligent Transport Systems and Services (ITS), mobile ITS-related services need efficient support from the underlying communication systems, which in turn requires profound knowledge of those needs. As a first step towards an optimal automatic choice of communication technologies in order to provide for seamless communications, this paper groups services into generic groups and presents a framework to classify their needs in terms of availability, performance, security and cost in a generic manner. These needs are consequently seen from the user’s perspective, but formulated in a way such that they can be matched towards known network parameters. Upon comparing needs with offers, the feasibility of a certain communication technology for a certain type of service can be determined both proactively and reactively, which helps to automatically select the right kind of connectivity in order to yield the desired degree of availability, performance, security and cost. We motivate for instance the need for determining and monitoring applicationperceived speeds, a multi-level security models and the one-stop service concept. We also provide an example on how these needs can be matched to offers by different networks.
|
|