Harmonic balance analysis for semiconductor lasers under large-signal modulation

The dynamic characteristics of an edge-emitting laser under large-signal modulation are analyzed in the frequency domain using a harmonic balance method on device level. The simulations reveal the nonlinearities of the carrier dynamics in the quantum well region which strongly influence the optical power in the higher harmonic

Exploiting Fluorescent Reporter Molecules for Process Analytical Technology (PAT): FH – HES

Process Analytical Technology (PAT) launched by the U.S. Food and Drug Administration (FDA) aims to ensure the quality of pharmaceutical products. One important tool to obtain a deeper process understanding is the use of modern real-time process sensors and analyzers. In this context an industrially accepted optical probe for turbidity measurement (Aquasant probe) has been adapted for on-line and real-time fluorescence measurement in (bio-)reactors. By tagging product proteins with fluorescent reporter molecules (e.g. GFP) it was possible to quantify product concentrations during a fermentation process with the new probe. The on-line obtained signal showed a high correlation to the off-line signal. This new method has remarkable advantages compared to classical off-line product lab analyses and can serve as a platform-independent quantification method of products to be used in either up- or downstream processing

Epidermal growth factor receptor is a marker for syncytiotrophoblastic cells in testicular germ cell tumors

The epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis, therapy and prognosis of various tumor types. The aim of this study was to investigate EGFR expression in a large series of testicular germ cell tumors (TGCTs). A total of 88 TGCTs (37 of pure type and 51 of mixed type) comprising a total of 44 seminoma, 49 embryonal carcinoma, 32 yolk sac tumor, 28 teratoma and 7 choriocarcinoma components were immunostained for EGFR. EGFR reactivity was observed in the stromal cells of embryonal carcinoma (29%) and in epithelial compartments of teratoma (71%). In addition, EGFR staining was consistently detected in syncytiotrophoblastic cells of choriocarcinoma, seminoma, embryonal carcinoma and yolk sac tumor components. EGFR staining, similar to β-human chorionic gonadotropin (HCG) immunohistochemistry, was efficiently able to identify syncytiotrophoblastic cells in TGCTs. This study shows that EGFR is expressed in a subset of testicular germ cell tumors and suggests that EGFR may be a useful marker for syncytiotrophoblastic cell

Elimination of chronic viral infection by blocking CD27 signaling

Neutralizing antibody (nAb) responses to lymphocytic choriomeningitis virus (LCMV) in mice and immunodeficiency virus and hepatitis C virus in humans are usually weak and slow to develop. This may be the result of structural properties of the surface glycoprotein, a low frequency of B cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nAbs. In this study, we show that during LCMV infection, CD27 signaling on CD4+ T cells enhances the secretion of interferon-γ and tumor necrosis factor-α. These inflammatory cytokines lead to the destruction of splenic architecture and immunodeficiency with reduced and delayed virus-specific nAb responses. Consequently, infection with the otherwise persistent LCMV strain Docile was eliminated after CD27 signaling was blocked. Our data provide a novel mechanism by which LCMV avoids nAb responses and suggest that blocking the CD27–CD70 interaction may be an attractive strategy to prevent chronic viral infection

Virus-induced Interferon α Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo

An effective type I interferon (IFN-α/β) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-α is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-α production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS®-sorted CD11cintCD11b−GR-1+ DCs show high IFN-α expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-α largely independent of IFNAR feedback signaling

Rapid Neutrophil Response Controls Fast-Replicating Intracellular Bacteria but Not Slow-Replicating Mycobacterium tuberculosis

Being one of the first cells to invade the site of infection, neutrophils play an important role in the control of various bacterial and viral infections. In the present work, the contribution of neutrophils to the control of infection with different intracellular bacteria was investigated. Mice were treated with the neutrophil-depleting monoclonal antibody RB6-8C5, and the time course of infection in treated and untreated mice was compared by using intracellular bacterial species and strains varying in virulence and replication rate. The results indicate that neutrophils are crucial for the control of fast-replicating intracellular bacteria, whereas early neutrophil effector mechanisms are dispensable for the control of the slow-replicating Mycobacterium tuberculosi

Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment

Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies. Materials and methods: Fifty microlitre containing 1×106 cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4ml of cisplatin-solution (100mg2/kg BW), cisplatin combined with the fibrin-based sealant Vivostat®, 4ml taurolidine 2%, repeated injection of 1μg of the chemokine CCL-19 at the tumour site and 4ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence. Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (±0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat® with significant decrease of the longest, widest and thickest diameter of the recurrence. Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat® significantly reduced the extent of local recurrenc

Protective T Cell–Independent Antiviral Antibody Responses Are Dependent on Complement

Complement is part of the innate immune system and one of the first lines of host defense against infections. Its importance was evaluated in this study in virus infections in mice deficient either in soluble complement factors (C3−/−, C4−/−) or in the complement signaling complex (complement receptor [CR]2−/−, CD19−/−). The induction of the initial T cell–independent neutralizing immunoglobulin (Ig)M antibody response to vesicular stomatitis virus (VSV), poliomyelitis virus, and recombinant vaccinia virus depended on efficient antigen trapping by CR3 and -4–expressing macrophages of the splenic marginal zone. Neutralizing IgM and IgG antibody responses were largely independent of CR2-mediated stimulation of B cells when mice were infected with live virus. In contrast, immunizations with nonreplicating antigens revealed an important role of B cell stimulation via CR2 in the switch to IgG. The complement cascade was activated after infection with VSV via the classical pathway, and active complement cleavage products augmented the effector function of neutralizing IgM and IgG antibodies to VSV by a factor of 10–100. Absence of the early neutralizing antibody responses, together with the reduced efficiency of neutralizing IgM in C3−/− mice, led to a drastically enhanced susceptibility to disease after infection with VSV