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| 2. |
- Hillmer, H., et al.
(författare)
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Wide continuously tunable 1.55 μm vertical air-cavity wavelength selective elements for filters and VCSELs using micromachined actuation
- 2005
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Ingår i: Opto-Ireland 2005. - : SPIE - International Society for Optical Engineering. - 0819458104 ; , s. 14-28
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Konferensbidrag (refereegranskat)abstract
- Tailored scaling allows the effectiveness of physical effects and mechanical stability to be enhanced. This is shown for micromachined 1.55μm vertical-resonator-based filters and VCSELs, capable of wide, continuous, and kink-free tuning by a single control parameter. Tuning is achieved by mechanically actuating one or several membranes in a vertical air-gap resonator including two highly reflective DBR mirrors. Electrostatically actuatable single-chip filters including InP/air-gap DBR's (3.5 periods) reveal a continuous tuning up to 14% of the absolute wavelength. Varying a reverse voltage (U=0 .. -3.2V) between the membranes (almost flat in the unactuated condition) a tuning range up to 142nm was obtained. Varying a reverse voltage (U=0 .. -28V) between the membranes (strained and curved in the unactuated condition) a tuning range up to 221nm was obtained. Optically pumped and continuously tunable 1.55μm VCSELs show 26nm spectral tuning range, 400μW maximum output power, and 57dBm SMSR. This two-chip VCSEL has a movable top mirror membrane, which is precisely designed to obtain a specific air-gap length and a tailored radius of curvature in order to efficiently support the fundamental optical mode of the plane-concave resonator. The curved top mirror DBR membrane consists of periodically alternating differently stressed silicon nitride and silicon dioxide multilayers. The lower InP-based part consists of the InP/GaInAsP bottom DBR and the GaInAsP active region.
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| 3. |
- Li, JH, et al.
(författare)
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IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.
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| 4. |
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| 5. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 6. |
- Hillmer, AM, et al.
(författare)
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Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes
- 2011
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 21:5, s. 665-675
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Tidskriftsartikel (refereegranskat)abstract
- Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA–PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.
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| 7. |
- Inaki, K, et al.
(författare)
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Transcriptional consequences of genomic structural aberrations in breast cancer
- 2011
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 21:5, s. 676-687
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Tidskriftsartikel (refereegranskat)abstract
- Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast cancer genomes. Herein, we show that 40%–54% of these structural genomic rearrangements result in different forms of fusion transcripts and that 44% are potentially translated. We find that single segmental tandem duplication spanning several genes is a major source of the fusion gene transcripts in both cell lines and primary tumors involving adjacent genes placed in the reverse-order position by the duplication event. Certain other structural mutations, however, tend to attenuate gene expression. From these candidate gene fusions, we have found a fusion transcript (RPS6KB1–VMP1) recurrently expressed in ∼30% of breast cancers associated with potential clinical consequences. This gene fusion is caused by tandem duplication on 17q23 and appears to be an indicator of local genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1.
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| 8. |
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| 9. |
- Tarraf, A., et al.
(författare)
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Continuously tunable 1.55-mu m VCSEL implemented by precisely curved dielectric top DBR involving tailored stress
- 2004
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Ingår i: IEEE Photonics Technology Letters. - 1041-1135 .- 1941-0174. ; 16:3, s. 720-722
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Tidskriftsartikel (refereegranskat)abstract
- We present an optically pumped and continuously tunable 1.55-mum vertical-cavity surface-emitting laser (VCSEL). The device shows. 26-mn spectral tuning range, 400-muW maximum output power, and 57-dBm side-mode suppression ratio. The VCSEL is implemented using a two-chip concept. The movable top mirror membrane is precisely designed to obtain a tailored air-gap length (L' = 16 mum) and a radius of curvature (ROC = 4.5 mm) in order to efficiently support the fundamental optical mode of the plane-concave resonator. It consists of a distributed Bragg reflector (DBR) with periodic, differently stressed silicon nitride and silicon dioxide multilayers implemented by plasma-enhanced chemical vapor deposition. The lower InP-based part, comprising the InP-InGaAsP bottom DBR and the active region, is grown monolithicaily using metal-organic vapor phase epitaxy.
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| 10. |
- Viotti, Corrado, et al.
(författare)
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The Endoplasmic Reticulum Is the Main Membrane Source for Biogenesis of the Lytic Vacuole in Arabidopsis
- 2013
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Ingår i: The Plant Cell. - : American Society of Plant Biologists. - 1040-4651 .- 1532-298X. ; 25:9, s. 3434-3449
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Tidskriftsartikel (refereegranskat)abstract
- Vacuoles are multifunctional organelles essential for the sessile lifestyle of plants. Despite their central functions in cell growth, storage, and detoxification, knowledge about mechanisms underlying their biogenesis and associated protein trafficking pathways remains limited. Here, we show that in meristematic cells of the Arabidopsis thaliana root, biogenesis of vacuoles as well as the trafficking of sterols and of two major tonoplast proteins, the vacuolar H+-pyrophosphatase and the vacuolar H+-adenosinetriphosphatase, occurs independently of endoplasmic reticulum (ER)-Golgi and post-Golgi trafficking. Instead, both pumps are found in provacuoles that structurally resemble autophagosomes but are not formed by the core autophagy machinery. Taken together, our results suggest that vacuole biogenesis and trafficking of tonoplast proteins and lipids can occur directly from the ER independent of Golgi function.
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