Transverse-mode coupling and diffraction loss in tunable Fabry-Perot microcavities

We report on measurements and modeling of the mode structure of tunable Fabry-Perot optical microcavities with imperfect mirrors. We find that non-spherical mirror shape and finite mirror size leave the fundamental mode mostly unaffected, but lead to loss, mode deformation, and shifted resonance frequencies at particular mirror separations. For small mirror diameters, the useful cavity length is limited to values significantly below the expected stability range. We explain the observations by resonant coupling between different transverse modes of the cavity and mode-dependent diffraction loss. A model based on resonant state expansion that takes into account the measured mirror profile can reproduce the measurements and identify the parameter regime where detrimental effects of mode mixing are avoided

Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology

Background: Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. Methods: Sera of HDM-allergic patients (positive skin prick test, CAP class 1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. Results: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients mono-sensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 1251-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were <3.9 kU/I. Conclusions: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed. (C) 2016 S. Karger AG, Base

Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice

Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3(Δm)) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3(Δm) mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3(Δm) CRCs. Moreover, STAT3(Δm) host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3(Δm) mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3(Δm) mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse

Toward personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.Fil: Niespodziana, Katarzyna. Vienna University of Technology; AustriaFil: Borochova, Kristina. Vienna University of Technology; AustriaFil: Pazderova, Petra. Vienna University of Technology; AustriaFil: Schlederer, Thomas. Vienna University of Technology; AustriaFil: Astafyeva, Natalia. Saratov State Medical University; RusiaFil: Baranovskaya, Tatiana. Belarusian Medical Academy of Post Diploma Studies; BielorrusiaFil: Barbouche, Mohamed Ridha. Institut Pasteur de Tunis; TúnezFil: Beltyukov, Evgeny. Ural State Medical University; RusiaFil: Berger, Angelika. Vienna University of Technology; AustriaFil: Borzova, Elena. Russian Medical Academy of Continuous Professional Education; RusiaFil: Bousquet, Jean. MACVIA; Francia. Humboldt-Universität zu Berlin; AlemaniaFil: Bumbacea, Roxana S.. University of Medicine and Pharmacy "Carol Davila"; RumaniaFil: Bychkovskaya, Snezhana. Krasnoyarsk Medical University; RusiaFil: Caraballo, Luis. Universidad de Cartagena; ColombiaFil: Chung, Kian Fan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Custovic, Adnan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Eiwegger, Thomas. University Of Toronto. Hospital For Sick Children; CanadáFil: Evsegneeva, Irina. Sechenov First Moscow State Medical University; RusiaFil: Emelyanov, Alexander. North-Western Medical University; RusiaFil: Errhalt, Peter. University Hospital Krems and Karl Landsteiner University of Health Sciences; AustriaFil: Fassakhov, Rustem. Kazan Federal University; RusiaFil: Fayzullina, Rezeda. Bashkir State Medical University; RusiaFil: Fedenko, Elena. NRC Institute of Immunology FMBA of Russia; RusiaFil: Fomina, Daria. Sechenov First Moscow State Medical University; RusiaFil: Gao, Zhongshan. Zhejiang University; ChinaFil: Giavina Bianchi, Pedro. Universidade de Sao Paulo; BrasilFil: Gotua, Maia. David Tvildiani Medical University; GeorgiaFil: Greber Platzer, Susanne. Vienna University of Technology; AustriaFil: Hedlin, Gunilla. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway

Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa

Towards personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people world-wide. While in the past few drugs for treatment of asthma were available, new treatment options are currently emerging which appear to be highly effective in certain subgroups of patients. Accordingly there is a need for biomarkers which allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on micro-arrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed which may discriminate two of the most common forms of asthma, i.e., allergen- and virus-triggered asthma. In this perspective we argue that classification of asthma patients according to these common trigger factors may open new possibilities for personalized management of asthma