Four-Junction Wafer-Bonded Concentrator Solar Cells Dimroth, Frank; Tibbits, Thomas N. D.; Niemeyer, Markus ...
IEEE journal of photovoltaics,
2016-Jan., 2016-1-00, 20160101, Volume:
6, Issue:
1
Journal Article
Peer reviewed
Open access
The highest solar cell conversion efficiencies are achieved with four-junction devices under concentrated sunlight illumination. Different cell architectures are under development, all targeting an ...ideal bandgap combination close to 1.9, 1.4, 1.0, and 0.7 eV. Wafer bonding is used in this work to combine materials with a significant lattice mismatch. Three cell architectures are presented using the same two top junctions of GaInP/GaAs but different infrared absorbers based on Germanium, GaSb, or GaInAs on InP. The modeled efficiency potential at 500 suns is in the range of 49-54% for all three devices, but the highest efficiency is expected for the InP-based cell. An efficiency of 46% at 508 suns was already measured by AIST in Japan for a GaInP/GaAs//GaInAsP/GaInAs solar cell and represents the highest independently confirmed efficiency today. Solar cells on Ge and GaSb are in the development phase at Fraunhofer ISE, and the first demonstration of functional devices is presented in this paper.
Oncoplastic surgery techniques lead to a rearrangement of the breast tissue and impede target definition during adjuvant radiotherapy (RT). The aim of this study was to assess local control rates ...after immediate oncoplastic surgery and adjuvant RT.
This study comprises 965 patients who underwent breast-conserving therapy and adjuvant RT between 01/2000 and 12/2005. 288 patients received immediate oncoplastic surgery (ONC) and 677 patients breast-conserving surgery only (NONC). All patients were treated with adjuvant external tangential-beam RT (total dose: 50/50.4 Gy; fraction dose 1.8/2.0 Gy). An additional boost dose of 10-16 Gy to the primary tumor bed was given in 900 cases (93.3%). Local control rates (LCR), Progression free survival (PFS) and overall survival (OS) were assessed retrospectively after a median follow-up period of 67 (Q25-Q75: 51-84) months.
No significant difference was found between ONC and NONC in regard to LCR (5-yr: ONC 96.8% vs. NONC 95.3%; p = 0.25). This held also true for PFS (5-yr: ONC 92.1% vs. NONC 89.3%; p = 0.09) and OS (5-yr: ONC 96.0% vs. NONC 94.8%; p = 0.53). On univariate analyses G2-3 (p = 0.04), a younger age (p = 0.01), T-stage (p < 0.01) lymph node involvement (p < 0.01) as well as triple negative tumors (p < 0.01) were identified as risk factors for local recurrence. In a propensity score stratified Cox-regression model no significant impact of oncoplastic surgery on local control rate was found (HR: 2.05, 95% CI 0.93; 4.51, p = 0.08).
Immediate oncoplastic surgery seems not to affect the effectiveness of adjuvant whole breast RT on local control rates in breast cancer patients.
Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic ...molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo.
Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry.
In wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects.
TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists.
Background
CXCR4 is a chemokine receptor frequently overexpressed in invasive breast cancer that has been shown to play a major role in signaling pathways involved in metastasis. The aim of this ...retrospective analysis was to assess the diagnostic performance of CXCR4-directed PET imaging in patients with breast cancer using the recently introduced CXCR4-targeted PET probe
68
Ga-Pentixafor.
Results
Thirteen patients with first diagnosis of breast cancer, four patients with recurrent disease after primary breast cancer, and one patient with axillary lymph node metastasis of unknown primary underwent CXCR4-targeted PET imaging using
68
Ga-Pentixafor. Maximum standardized uptake values (SUVmax) and tumor-to-background (T/B) ratios of tumor lesions were measured and compared with pathological prognostic factors and molecular subtypes.
18
F-FDG PET/CT images were available in 8/18 cases and were compared semi-quantitatively. Comparison with CXCR4 expression determined by immunohistochemistry was performed in 7/18 patients.
Nine of 13 primary breast cancers were visually detectable on
68
Ga-Pentixafor PET images (mean SUVmax of 3.0). The visually undetectable lesions included both cases of invasive lobular carcinoma (ILC) and two cases of invasive carcinoma of no special type (NST) without any hormone receptor and HER2 expression (triple negative). Metastases of recurrent breast cancer and unknown primary cancer were visually detectable in all five cases, exhibiting a mean SUVmax of 3.5.
18
F-FDG PET demonstrated higher SUVmax in all patients compared to
68
Ga-Pentixafor PET. A correlation between SUVmax obtained from
68
Ga-Pentixafor PET and prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, proliferation index, tumor grade, or molecular subtypes was not observed.
Conclusions
CXCR4-directed PET imaging in patients with primary and recurrent breast cancer is feasible; however, tumor detectability is significantly lower compared to
18
F-FDG PET. Moreover, we did not find any correlation between aforementioned prognostic factors of breast cancer and CXCR4-targeted tracer accumulation. Based on these results in a small patient cohort, CXCR4-targeted PET imaging does not seem to be suitable as a general diagnostic tool for imaging of breast cancer. Future CXCR4 imaging studies should investigate whether this modality might be useful in more specific applications, e.g., in therapeutic approaches especially under the view of current developments in targeted immune cell and immune checkpoint inhibitory therapy.
In hepatitis C virus (HCV) infection, morbidity and mortality often result from extrahepatic disease manifestations. We provide evidence for a role of receptors of the innate immune system in virally ...induced inflammation of the endothelium in vitro and in vivo. Corresponding to the in vitro finding of an HCV-dependent induction of proinflammatory mediators in endothelial cells, mice treated with poly (I:C) exhibit a significant reduction in leukocyte rolling velocity, an increase in leukocyte adhesion to the vessel wall and an increased extravasation of leukocytes. HCV directly promotes activation, adhesion and infiltration of inflammatory cells into the vessel wall by activation of endothelial viral receptors. Poly (I:C) induces the expression of TLR3 in vivo and hereby allows for amplification of all of the aforementioned responses upon viral infection. Proinflammatory effects of viral RNA are specifically mediated by TLR3 and significantly enhanced by tumor necrosis factor alpha (TNFα). HCV-RNA induces the endothelial expression of TNFα and TNFα receptor subtype 2 and we provide evidence that leucocyte adhesion and transmigration in response to activation of viral RNA receptors seem to depend on expression of functional TNFR2. Our results demonstrate that endothelial cells actively participate in immune mediated vascular inflammation caused by viral infections.
Introduction. Inflammation and endothelium-derived superoxides are important pathomechanisms in atherothrombotic diseases. We could previously show that the tyrosine phosphatase SHP-1 acts as a ...negative regulator in endothelial superoxide production. In this study we investigated the influence of SHP-1 on platelet-endothelium interaction and arterial thrombosis in TNFα-induced endothelial inflammation in vivo. Methods. Arteriolar thrombosis and platelet rolling in vivo were investigated in C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. Results. Inhibition of SHP-1 by the specific pharmacological inhibitor sodium stibogluconate did not significantly enhance platelet-endothelium interaction in vivo under physiological conditions but led to an augmented fraction of rolling platelets in TNFα-induced systemic inflammation. Accordingly, ferric-chloride-induced arteriolar thrombus formation, which was already increased by SHP-1 inhibition, was further enhanced in the setting of TNFα-induced inflammation. Platelet aggregation in vitro as well as ex vivo was not influenced by SHP-1-inhibition. In cultured endothelial cells, sodium stibogluconate increased TNFα-induced surface expression of p-selectin and von Willebrand factor. Additionally, TNFα increased SHP-1 activity and protein expression. Conclusions. The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular hemostasis in vivo, which is crucial in TNFα-induced endothelial inflammation where it may serve as an autoinhibitory molecule to prevent excess inflammatory response and thrombus formation.
Objective
To assess migration of CD34
+
human stem cells to the bone marrow of athymic mice by using magnetic resonance (MR) imaging and Resovist, a contrast agent containing superparamagnetic iron ...oxide (SPIO) particles.
Methods
All animal and human procedures were approved by our institution’s ethics committee, and women had given consent to donate umbilical cord blood (UCB). Balb/c-AnN Foxn1
nu
/Crl mice received intravenous injection of 1 × 10
6
(
n
= 3), 5 × 10
6
(
n
= 3) or 1 × 10
7
(
n
= 3) human Resovist-labelled CD34
+
cells; control mice received Resovist (
n
= 3). MR imaging was performed before, 2 and 24 h after transplantation. Signal intensities of liver, muscle and bone marrow were measured and analysed by ANOVA and post hoc Student’s
t
tests. MR imaging data were verified by histological and immunological detection of both human cell surface markers and carboxydextran-coating of the contrast agent.
Results
CD34
+
cells were efficiently labelled by Resovist without impairment of functionality. Twenty-four hours after administration of labelled cells, MR imaging revealed a significant signal decline in the bone marrow, and histological and immunological analyses confirmed the presence of transplanted human CD34
+
cells.
Conclusion
Intravenously administered Resovist-labelled CD34
+
cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology.
We investigated whether KIT signaling was sufficient to maintain human hematopoietic stem cells in culture or whether, as with murine stem cells, signaling through glycoprotein 130 (gp130) is ...additionally required. Sorted CD34(+)CD133(+)(CD33/CD38/CD71)(-) cells from human umbilical cord blood (UCB) were cultured in the presence of combinations of KIT-ligand (KL) and the gp130 stimulating molecule oncostatin M (OSM). We found that OSM increased KL-induced proliferation, which was accompanied by an expansion in numbers of mature progenitors colony-forming cells (CFC, CAFCw2). More primitive progenitors, CAFCw6 and long-term culture-CFC, were not maintained by KL as a single factor. Although addition of OSM did not improve survival, the KL/OSM combination showed improved maintenance of immature progenitors as well as higher CD34 expression. Similarly, both KL and OSM were required to maintain NOD/SCID-repopulating activity. In experiments to investigate the underlying mechanism, we found that extracellular signal-regulated kinase (ERK) and its downstream target p90 ribosomal S6 kinase were activated by KL and downregulated by the inclusion of OSM during stimulation. The p38 mitogen-activated protein kinase (p38 MAPK) was not modulated by either KL or OSM. Indeed, many of the effects of OSM (increased cell division, maintenance of CFC, and maintenance of high CD34 expression) could be mimicked by using the mitogen-activated protein kinase kinase inhibitor U0126. More importantly, NOD/SCID-repopulating activity was preserved in the KL/U0126-stimulated cells, but not in cells stimulated with a combination of KL and the p38 MAPK inhibitor SB203580. Our results show that the loss of repopulating activity during KL stimulation is counteracted by OSM through the downregulation of ERK pathway signaling. Disclosure of potential conflicts of interest is found at the end of this article.
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