Extracting Urban Morphology for Atmospheric Modeling from Multispectral and SAR Satellite Imagery

This paper presents an approach designed to derive an urban morphology map from satellite data while aiming to minimize the cost of data and user interference. The approach will help to provide updates to the current morphological databases around the world. The proposed urban morphology maps consist of two layers: 1) Digital Elevation Model (DEM) and 2) land cover map. Sentinel-2 data was used to create a land cover map, which was realized through image classification using optical range indices calculated from image data. For the purpose of atmospheric modeling, the most important classes are water and vegetation areas. The rest of the area includes bare soil and built-up areas among others, and they were merged into one class in the end. The classification result was validated with ground truth data collected both from field measurements and aerial imagery. The overall classification accuracy for the three classes is 91 %. TanDEM-X data was processed into two DEMs with different grid sizes using interferometric SAR processing. The resulting DEM has a RMSE of 3.2 meters compared to a high resolution DEM, which was estimated through 20 control points in flat areas. Comparing the derived DEM with the ground truth DEM from airborne LIDAR data, it can be seen that the street canyons, that are of high importance for urban atmospheric modeling are not detectable in the TanDEM-X DEM. However, the derived DEM is suitable for a class of urban atmospheric models. Based on the numerical modeling needs for regional atmospheric pollutant dispersion studies, the generated files enable the extraction of relevant parametrizations, such as Urban Canopy Parameters (UCP).Peer reviewe

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots

Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma

Interleukin 10 (IL-10) is an immunosuppressive factor and has been detected in tumour cell cultures of renal cell carcinoma and of malignant melanoma. IL-10 has been described as a cytokine of the Th2 response; it is able to suppress antigen-presenting cells (APCs) and may lead to down-regulation of HLA class I and II molecules on dendritic cells and to anergy of T-lymphocytes. We evaluated pretreatment serum levels of soluble IL-10 and various clinical parameters to determine their prognostic value in 80 advanced renal cell carcinoma patients seen at our institution between May 1990 and April 1996. For statistical evaluation we used both univariate and multivariate Cox proportional hazards models. An elevated pretreatment serum level of IL-10 was a statistically independent predictor of unfavourable outcome (P < 0.0028), in addition to the well-known clinical and biochemical risk factors. These data support risk stratification for future therapeutic trials and identify a predictor which needs to be validated in prospective studies and may potentially influence decision making in palliative management of patients with metastatic renal cell carcinoma. These data also suggest a potential role of IL-10 in the development of advanced renal cell carcinoma and in the future design of therapeutic strategies. © 1999 Cancer Research Campaig

The free β-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

The free β-subunit of human chorionic gonadotropin β is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin β expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin β in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin β in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin β, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin β were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin β levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l−1, P=0.0029). In multivariate analysis human chorionic gonadotropin β, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin β is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin β in serum may be used to identify patents with increased risk of progressive disease

Genetic approaches to understanding the causes of stuttering

Stuttering is a common but poorly understood speech disorder. Evidence accumulated over the past several decades has indicated that genetic factors are involved, and genetic linkage studies have begun to identify specific chromosomal loci at which causative genes are likely to reside. A detailed investigation of one such region on chromosome 12 has identified mutations in the GNPTAB gene that are associated with stuttering in large families and in the general population. Subsequent studies identified mutations in the functionally related GNPTG and NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway that generates the Mannose 6-phosphate signal, which directs a diverse group of enzymes to their target location in the lysosome of the cell. While mutations in these three genes can be identified in less than 10% of cases of familial stuttering, this knowledge allows a variety of new studies that can help identify the neuropathology that underlies this disorder

Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany - a first analysis of a prospective observational study

OBJECTIVE: Characterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS). METHODS: Setting: Charité Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charité University hospital. Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charité Fatigue Center from July to November 2020. Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded. RESULTS: The median age was 36.5, range 22–62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14–32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15–90) of 100 (healthy) and Short Form 36 (SF-36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p=0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (p=0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients. CONCLUSIONS: Chronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed

Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine.

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind assessment of the distribution of IL-10 levels in the culture supernatants, a cutoff of 200 pg/ml was used to define high versus low IL-10 producers. Cox regression model was used for multivariate analysis. Overall survival was calculated using the Kaplan-Meier method, and survival curves were compared with the log-rank test. RESULTS: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The median OS was significantly worse for high compared with low IL-10 producers (10.5 months vs. 42 months; P = 0.022). In stage III patients, the multivariate hazard ratio for high versus low IL-10 producers was 2.92 (95% CI, 1.04-8.20; P = 0.041). The corresponding hazard ratio in stage IV patients was 0.92 (95% CI, 1.04-8.20; P = 0.888). CONCLUSIONS: High IL-10 production in the tumor microenvironment could be a determinant of clinical outcomes in stage III melanoma patients receiving autologous melanoma cell vaccine