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  • 1
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 73, No. 7 ( 2018-07-01), p. 1984-1988
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
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  • 2
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 39, No. 45 ( 2019-11-06), p. 9013-9027
    Abstract: Cleavage of amyloid precursor protein (APP) by β-secretase BACE1 initiates the production and accumulation of neurotoxic amyloid-β peptides, which is widely considered an essential pathogenic mechanism in Alzheimer's disease (AD). Here, we report that BACE1 is essential for normal auditory function. Compared with wild-type littermates, BACE1 −/− mice of either sex exhibit significant hearing deficits, as indicated by increased thresholds and reduced amplitudes in auditory brainstem responses (ABRs) and decreased distortion product otoacoustic emissions (DPOAEs). Immunohistochemistry revealed aberrant synaptic organization in the cochlea and hypomyelination of auditory nerve fibers as predominant neuropathological substrates of hearing loss in BACE1 −/− mice. In particular, we found that fibers of spiral ganglion neurons (SGN) close to the organ of Corti are disorganized and abnormally swollen. BACE1 deficiency also engenders organization defects in the postsynaptic compartment of SGN fibers with ectopic overexpression of PSD95 far outside the synaptic region. During postnatal development, auditory fiber myelination in BACE1 −/− mice lags behind dramatically and remains incomplete into adulthood. We relate the marked hypomyelination to the impaired processing of Neuregulin-1 when BACE1 is absent. To determine whether the cochlea of adult wild-type mice is susceptible to AD treatment-like suppression of BACE1, we administered the established BACE1 inhibitor NB-360 for 6 weeks. The drug suppressed BACE1 activity in the brain, but did not impair hearing performance and, upon neuropathological examination, did not produce the characteristic cochlear abnormalities of BACE1 −/− mice. Together, these data strongly suggest that the hearing loss of BACE1 knock-out mice represents a developmental phenotype. SIGNIFICANCE STATEMENT Given its crucial role in the pathogenesis of Alzheimer's disease (AD), BACE1 is a prime pharmacological target for AD prevention and therapy. However, the safe and long-term administration of BACE1-inhibitors as envisioned in AD requires a comprehensive understanding of the various physiological functions of BACE1. Here, we report that BACE1 is essential for the processing of auditory signals in the inner ear, as BACE1-deficient mice exhibit significant hearing loss. We relate this deficit to impaired myelination and aberrant synapse formation in the cochlea, which manifest during postnatal development. By contrast, prolonged pharmacological suppression of BACE1 activity in adult wild-type mice did not reproduce the hearing deficit or the cochlear abnormalities of BACE1 null mice.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2019
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  BMC Pulmonary Medicine Vol. 22, No. 1 ( 2022-12)
    In: BMC Pulmonary Medicine, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: In Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF). Methods From February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data. Results In total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized. Conclusions SARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.
    Type of Medium: Online Resource
    ISSN: 1471-2466
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2059871-3
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  • 4
    In: The Lancet Diabetes & Endocrinology, Elsevier BV, Vol. 12, No. 2 ( 2024-02), p. 119-131
    Type of Medium: Online Resource
    ISSN: 2213-8587
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
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  • 5
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 10 ( 2022-09-28), p. e4167-e4176
    Abstract: Endothelial dysfunction may occur early in the development of cardiovascular and metabolic diseases; however, it remains often underestimated and studies rarely discriminate between diabetes types. We have examined endothelial function and its determinants during the early course of type 1 and type 2 diabetes. Methods Caucasian participants of the prospective German Diabetes Study (GDS) with known diabetes duration & lt;1 year (n = 398) or without diabetes, but of similar age, body mass index (BMI) and sex distribution (n = 109), underwent measurements of flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD). Whole-body insulin sensitivity (M-value) was assessed by hyperinsulinemic–euglycemic clamps and physical fitness (VO2max) by spiroergometry. A subset of individuals with type 1 or type 2 diabetes (n = 108) was re-evaluated after 5 years. Results At baseline, neither FMD nor NMD differed between people with diabetes and the matched glucose-tolerant groups. At the 5-year follow-up, decline in FMD (–13.9%, P = .013) of persons with type 2 diabetes was independent of age, sex, and BMI, but associated with baseline adipose tissue insulin resistance and indices of liver fibrosis. The M-value decreased in both type 1 and type 2 diabetes groups by 24% and 15% (both P  & lt; .001, respectively) over 5 years. Higher HbA1c, lower M-value, and lower VO2max at baseline was associated with lower FMD in both type 1 and type 2 diabetes. Conclusion Endothelial function decreases during the early course of type 2 diabetes. In addition to age and BMI, insulin sensitivity at diagnosis was the best predictor of progressive impairment in endothelial function in type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 6
    In: Journal of the ASABE, American Society of Agricultural and Biological Engineers (ASABE), Vol. 65, No. 4 ( 2022), p. 881-901
    Abstract: Highlights Upper Rio Grande Basin increased population by 80% with flat public supply water withdrawals from 1980 to 2015. Significant decreasing trends in precipitation, snowmelt rate, streamflow, baseflow, and ET were observed. Simulated near-native streamflow was greater than previous estimates, particularly for higher flow years. More precipitation as rain, slower snowmelt, less streamflow, and greater baseflow fraction impact water security. Abstract. The Upper Rio Grande Basin (URGB) is a critical international water resource under pressure from a myriad of climatic, ecological, infrastructural, water-use, and legal constraints. The objective of this study is to provide a comprehensive assessment of the spatial distribution and temporal trends of selected water-budget components (snow processes, evapotranspiration (ET), streamflow processes, and groundwater storage) using integrated analyses, such as watershed modeling and water availability and use data in the URGB over the past three decades. A spatially distributed snow evolution modeling system simulated snowpack processes over 34 years (1984–2017). It highlighted snow water equivalent declines from -35 to -77 mm/decade with widespread variability across elevation zones and land cover types. Gridded actual ET data from the SSEBop model were developed and tested for the URGB and demonstrated that all land-cover types had significant decreasing trends (1986-2015) ranging from -14 to -80 mm/decade. Conductivity-mass-balance (CMB) hydrograph separation results found that baseflow forms a large component of total streamflow, ranging from 29 to 69% (49% average) of total streamflow at 17 URGB sites upstream of Albuquerque, NM. Three of 4 graphical hydrograph separation methods in the U.S. Geological Survey Groundwater Toolbox were found to be inappropriate for estimating baseflow in the URGB; the most promising method, baseflow index (BFI) Standard, was optimized using CMB data and tested at three URGB sites, with resulting overestimation of 0 to 47%. Simulated changes in groundwater storage were extracted from historical and recent groundwater-flow models of select alluvial basins (San Luis, Española, Middle Rio Grande, and Tularosa-Hueco). In general, decreases in groundwater storage were observed from 1903 to 2013 except for the San Luis alluvial basin (Colorado), where periods of recovery are observed. The PRMS hydrologic model was successfully calibrated for 9 near-native subbasins (Nash-Sutcliffe efficiency 0.47 to 0.85) and parameters translated to the remaining subbasins; compared to simulated near-native flows (with minimal influence of reservoirs or diversions), observed Rio Grande streamgage flows demonstrated reductions of 40% or more for New Mexico and Texas areas of the basin. Significant decreasing trends (1980-2015) in precipitation, snowmelt rate, streamflow, and baseflow were observed at many of the 12 streamgage basins studied, which suggests that the decreasing trends for actual ET may be related to overall decreasing water availability in the basin, with negative implications for agricultural production and groundwater abstraction. Water security concerns arise from our findings of higher fraction precipitation as rain, slower snowmelt rates leading to decreasing streamflow production, and an increasing fraction of baseflow, all of which will affect the timing and magnitude of water available for human needs in the basin. Keywords: Baseflow, Evapotranspiration, Groundwater, Snow, Streamflow, Watershed model, Water supply.
    Type of Medium: Online Resource
    ISSN: 2769-3287
    Language: English
    Publisher: American Society of Agricultural and Biological Engineers (ASABE)
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2023
    In:  ISPRS Open Journal of Photogrammetry and Remote Sensing Vol. 9 ( 2023-08), p. 100043-
    In: ISPRS Open Journal of Photogrammetry and Remote Sensing, Elsevier BV, Vol. 9 ( 2023-08), p. 100043-
    Type of Medium: Online Resource
    ISSN: 2667-3932
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 3106021-3
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  • 8
    Online Resource
    Online Resource
    Annual Reviews ; 2009
    In:  Annual Review of Entomology Vol. 54, No. 1 ( 2009-01-01), p. 303-321
    In: Annual Review of Entomology, Annual Reviews, Vol. 54, No. 1 ( 2009-01-01), p. 303-321
    Abstract: The western corn rootworm, Diabrotica virgifera virgifera LeConte, is an established insect pest of maize (Zea mays L.) in North America. The rotation of maize with another crop, principally soybeans, Glycine max (L.), was the primary management strategy utilized by North American producers and remained highly effective until the mid-1990s. In 1995, widespread and severe root injury occurred in east-central Illinois and northern Indiana maize fields that had been annually rotated with soybeans on a regular basis for several decades. The failure of this cultural tactic from a pest management perspective was attributed to a behavioral adaptation by a variant western corn rootworm that had lost fidelity to maize for egg laying. In 1992, an infestation of western corn rootworm was found within a small maize field near the Belgrade Airport. By 2007, the presence of this insect pest had been confirmed in 20 European countries. More recent molecular studies have confirmed that at least three separate invasions (until 2004) of western corn rootworms have occurred in Europe, increasing the risk that rotation-resistant western corn rootworms will be introduced into a new continent. Although biological control and use of conventional resistant maize hybrids have not achieved widespread success in the management of western corn rootworms in North America, these tactics are being evaluated in Europe.
    Type of Medium: Online Resource
    ISSN: 0066-4170 , 1545-4487
    URL: Issue
    RVK:
    Language: English
    Publisher: Annual Reviews
    Publication Date: 2009
    detail.hit.zdb_id: 1473785-1
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  PFG – Journal of Photogrammetry, Remote Sensing and Geoinformation Science Vol. 91, No. 4 ( 2023-08), p. 313-334
    In: PFG – Journal of Photogrammetry, Remote Sensing and Geoinformation Science, Springer Science and Business Media LLC, Vol. 91, No. 4 ( 2023-08), p. 313-334
    Abstract: A responsible use of energy resources is currently more important than ever. For the effective insulation of industrial plants, a three-camera measurement system was, therefore, developed. With this system, the as-built geometry of pipelines can be captured, which is the basis for the production of a precisely fitting and effective insulation. In addition, the digital twin can also be used for Building Information Modelling, e.g. for planning purposes or maintenance work. In contrast to the classical approach of processing the images by calculating a point cloud, the reconstruction is performed directly on the basis of the object edges in the image. For the optimisation of the, initially purely geometrically calculated components, an adjustment approach is used. In addition to the image information, this approach takes into account standardised parameters (such as the diameter) as well as the positional relationships between the components and thus eliminates discontinuities at the transitions. Furthermore, different automation approaches were developed to facilitate the evaluation of the images and the manual object recognition in the images for the user. For straight pipes, the selection of the object edges in one image is sufficient in most cases to calculate the 3D cylinder. Based on the normalised diameter, the missing depth can be derived approximately. Elbows can be localised on the basis of coplanar neighbouring elements. The other elbow parameters can be determined by matching the back projection with the image edges. The same applies to flanges. For merging multiple viewpoints, a transformation approach is used which works with homologous components instead of control points and minimises the orthogonal distances between the component axes in the datasets.
    Type of Medium: Online Resource
    ISSN: 2512-2789 , 2512-2819
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2888495-4
    detail.hit.zdb_id: 2886415-3
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  • 10
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: Recent studies identified distinct endotypes of diabetes with differences in metabolic features and in risk for diabetes-related comorbidities. Of note, persons allocated to the severe insulin resistant diabetes (SIRD) endotype, who show increased prevalence of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), are more frequently carriers of the G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene. This SNP associates with increased risk of NAFLD yet the association between the presence of the PNPLA3 SNP and CKD remains controversial. The present study examined whether this SNP differently associates with CKD in endotypes of recent-onset diabetes. Participants with newly diagnosed diabetes (n=707) from the prospective German Diabetes Study underwent k-means clustering, genotyping, magnetic resonance spectroscopy to determine hepatocellular lipid content (HCL) and laboratory analyses to calculate the glomerular filtration rates (eGFR). SIRD had the lowest eGFR and highest HCL compared to severe insulin deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes clusters (all p & lt;0.05). HCL was negatively associated with eGFR (r=-0.287, p & lt;0.01) across all groups. Further stratification by PNPLA3 G-allele carrier status did not reveal any association between HCL and eGFR in any of the diabetes types, irrespective of G-allele carrier status. However, with declining eGFR the proportion of G-allele carriers increased from 44% for eGFR & gt;60 ml/min to 52% for eGFR & lt;60 ml/min (p & lt;0.05). In conclusion, increased hepatic lipid content is associated with reduced kidney function across all diabetes endotypes. This association is independent of the presence of the PNPLA3 polymorphism in newly diagnosed diabetes, but there might be role for PNPLA3 for the severity of CKD. Disclosure O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. Y. Kupriyanova: None. J. Kotzka: None. K. Bódis: None. M. Schön: None. M. Bombrich: None. C. Möser: None. K. Prystupa: Other Relationship; Berlin-Chemie AG. H. Al-Hasani: None. V. Schrauwen-Hinderling: None. K. Jandeleit-Dahm: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi. Funding German Research Foundation; European Foundation for the Study of Diabetes; German Diabetes Association; German Federal Ministry of Education and Research; Heinrich Heine University
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
    detail.hit.zdb_id: 1501252-9
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