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    Internationale Immobilienforschung in Wissenschaft und Praxis

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    Immobilienprofessionals müssen sich in vielen Disziplinen auskennen

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    Hydrogel microspheres evading alveolar macrophages for sustained pulmonary protein delivery

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    Pulmonary delivery is a highly attractive alternative to injections for biologics such as therapeutic proteins. However, bioavailabilities generally suffer from the presence of phagocytic cells that clear particulate matter entering the lung. In this study, microgel particles were developed using an all-aqueous two-phase system approach and evaluated for their efficacy as an inhalable controlled release system. Norbornene- and thiol-modified four- and eight-armed poly (ethylene glycol) with an average molecular mass of 10,000 Da were prepared as macromonomers for microgel formation. Emulsions of precursor solution droplets containing macromonomers and Irgacure 2959 as photocatalyst were prepared in a dextran solution. Irradiation with UV light was used to covalently crosslink the droplets by triggering the thiol-ene reaction. The resulting microgels were processed to dry powder inhaler formulations, and respirable aerodynamic sizes were assessed in vitro. Microgels were loaded with the model proteins lysozyme and bovine serum albumin, with encapsulation efficiencies of 51.5% and 73.6%, respectively. Depending on the macromonomer type, protein-loaded microgels released their cargo over a 6–14 day period. In an MTT assay, the particles did not show significant cytotoxicity, and their recognition by alveolar macrophages was considerably lower than for polystyrene control particles. This makes the microgels a promising pulmonary delivery system for proteins and other biologics

    Exciton broadening in WS2 /graphene heterostructures

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    We have used optical spectroscopy to observe spectral broadening of WS2 exciton reflectance peaks in heterostructures of monolayer WS2 capped with mono- to few-layer graphene. The broadening is found to be similar for the A and B excitons and on the order of 5–10 meV. No strong dependence on the number of graphene layers was observed within experimental uncertainty. The broadening can be attributed to charge- and energy-transfer processes between the two materials, providing an observed lower bound for the corresponding time scales of 65 fs

    Influence of perceptual cues and conceptual information on the activation and reduction of claustrophobic fear

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    Background: Fear reactions in phobic patients can be activated by specific perceptual cues (C) or by conceptual fear-related information (I). An earlier study with spider phobic participants documented that perceptual stimuli are particularly potent to trigger fear responses. Because fear of spiders is activated by very circumscribed stimuli, we set out to investigate whether another phobia with more contextual fear-elicitation (i.e., a situational phobia) would yield similar patterns. Thus, we investigate the two paths of fear activation (cues vs. information) and fear reduction during exposure in claustrophobic patients. Method: Forty-eight claustrophobic patients and 48 healthy control participants were randomly assigned to one of three virtual reality exposure conditions: C, I, or a combination of both (CI). Exposure lasted 5 min and was repeated 4 times. Self-report and physiological reactions were assessed. Results: Claustrophobic patients experienced more initial self-reported fear when confronted with fear relevant perceptual cues than conceptual information, when the perceptual cues were combined with conceptual information there was no significant enhancement. Furthermore, fear habituated more in the perceptual condition. For the physiological parameters, groups differed and in claustrophobic patients heart rate decreased differently in the conditions. Limitations: Longer exposure duration and long-term effects of the manipulation were not investigated. Conclusion: We found similar patterns in a situational phobia as compared to a specific-cue related phobia (animal type). Thus, once more this highlights the central role of visual cues in phobic fear and the potential of virtual reality for conducting exposure therapy. (C) 2015 Elsevier Ltd. All rights reserved

    Decreased femoral periprosthetic bone mineral density: a comparative study using DXA in patients after cementless total hip arthroplasty with osteonecrosis of the femoral head versus primary osteoarthritis

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    Introduction Trabecular properties in osteonecrosis of the femoral head (ONFH) are altered for bone volume and structure in the femoral head and proximal femoral canal. We analysed the periprosthetic bone mineral density (BMD) as a correlate to bony ingrowth in patients with ONFH who received a cementless THA. Materials and methods We performed a matched-pair analysis of 100 patients with ONFH (n = 50) and primary osteoarthritis (n = 50) who received the same, unilateral cementless THA. We compared the periprosthetic BMD 5 years after surgery by means of dual energy X-ray absorptiometry (DXA) analysing the seven femoral regions of interest (ROIs) according to Gruen. Results Within the ONFH group, significantly lower BMD values were found in the ROI 1 and 7 (p < 0.05). No statistically significant difference was found for ROIs 2-6. Conclusions An altered periprosthetic bone stock in the proximal femur in patients with prior ONFH might be a possible risk factor for premature loosening of the femoral stem in THA. Surgeons need to consider coating and fixation philosophy of cementless implants when choosing the right stem for patients with ONFH

    miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction

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    Background: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. Methods: We investigated gene expression profiles of tumor-reactive CD8(+) T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8(+) T cells from 25 RCC patients compared to 15 healthy volunteers. Results: We observed that CD8(+) T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8(+) T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8(+) T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Conclusions: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8(+) T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo

    Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

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    Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields

    Prediction of Appropriate Shocks Using 24-Hour Holter Variables and T-Wave Alternans After First Implantable Cardioverter-Defibrillator Implantation in Patients With Ischemic or Nonischemic Cardiomyopathy

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    In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T-wave alternans testing and 24-hour Holier variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holler for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 +/- 15 months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT-proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (>= 1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p = 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p = 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks (clinicaltrials.gov: NCT02010515). (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY NC -ND license (http://creativecommons.orgflicenses/by-nc-nd/4.00. (Am J Cardiol 2016;118:86-94

    Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells

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    Chronic graft-versus-host disease(cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases <= 1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3(+)CD56(bright) natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates
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