89 results on '"C. Koch"'
Search Results
2. Evaluating hydrologic region assignment techniques for ungaged basins in Alaska, <scp>USA</scp>
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Theodore B. Barnhart, William H. Farmer, John C. Hammond, Graham A. Sexstone, Janet H. Curran, Joshua C. Koch, and Jessica M. Driscoll
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Environmental Chemistry ,General Environmental Science ,Water Science and Technology - Published
- 2022
3. Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment
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Jian Cheng, Forrest C. Koch, Wei Wen, Perminder S. Sachdev, Peter J. Basser, Jiyang Jiang, Haichao Zhao, and Tao Liu
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Male ,orientation change ,Uncinate fasciculus ,Nerve Fibers, Myelinated ,behavioral disciplines and activities ,White matter ,amnestic mild cognitive impairment ,Atrophy ,Neuroimaging ,Alzheimer Disease ,Fasciculus ,medicine ,Humans ,Cognitive Dysfunction ,Radiology, Nuclear Medicine and imaging ,Effects of sleep deprivation on cognitive performance ,Research Articles ,Aged ,Aged, 80 and over ,Radiological and Ultrasound Technology ,biology ,business.industry ,Superior longitudinal fasciculus ,Alzheimer's disease ,biology.organism_classification ,medicine.disease ,White Matter ,geometric microstructure ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Neurology ,Corticospinal tract ,Female ,Amnesia ,Neurology (clinical) ,Anatomy ,business ,Neuroscience ,Research Article - Abstract
White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer's disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called “Director Field Analysis” (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals from the Alzheimer's Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI individuals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI., Orientational changes may be partially caused by the expansion of lateral ventricle, white matter atrophy and gray matter atrophy in Alzheimer's disease. The inferior longitudinal fasciculus and uncinate fasciculus may be more vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients' cognitive impairment in amnestic mild cognitive impairment.
- Published
- 2021
4. Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen
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Christoph Münch, Susanne Petri, Claudia D. Wurster, Albert C. Ludolph, Julian Grosskreutz, Olivia Schreiber-Katz, Tim Hagenacker, Bertram Walter, Markus Weiler, Robert Steinbach, Ramona Griep, Benjamin Stolte, A. Rödiger, Zeljko Uzelac, Maren Freigang, Jan C. Koch, Jenny Norden, Marcel Gaudlitz, Ute Weyen, Susanne Spittel, André Maier, Thomas Meyer, Alma Osmanovic, René Günther, Dagmar Kettemann, and Johannes Dorst
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Adult ,medicine.medical_specialty ,Therapieerfolg ,Adolescent ,Medizin ,Muscular atrophy, Spinal ,Drug therapy ,Oligonucleotides ,Disease ,treatment satisfaction ,Pharmakotherapie ,Muscular Atrophy, Spinal ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Spinale Muskelatrophie ,Internal medicine ,medicine ,Humans ,ddc:610 ,Prospective Studies ,030212 general & internal medicine ,Treatment outcome ,Amyotrophic lateral sclerosis ,Aged ,Motivation ,Adult patients ,drug therapy [Muscular Atrophy, Spinal] ,spinal muscle atrophy ,business.industry ,nusinersen ,Spinal muscular atrophy ,Middle Aged ,treatment expectations ,medicine.disease ,SMA ,Trunk ,Neurology ,Perception ,Nusinersen ,Observational study ,Neurology (clinical) ,business ,DDC 610 / Medicine & health ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,030217 neurology & neurosurgery - Abstract
Background and purpose This was an investigation of treatment expectations and of the perception of therapy in adult patients with 5q-associated spinal muscular atrophy (5q-SMA) receiving nusinersen. Methods A prospective, non-interventional observational study of nusinersen treatment in adult 5q-SMA patients was conducted at nine SMA centers in Germany. The functional status, treatment expectations and perceived outcomes were assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale—extended (ALS-FRS-ex), the Measure Yourself Medical Outcome Profile (MYMOP2), the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and the Net Promoter Score (NPS). Results In all, 151 patients were included with a median age of 36 years (15–69 years). SMA type 3 (n = 90, 59.6%) prevailed, followed by type 2 (33.8%) and type 1 (6.6%). In SMA types 1–3, median ALS-FRS-ex scores were 25, 33 and 46 (of 60 scale points), respectively. MYMOP2 identified distinct treatment expectations: head verticalization (n = 13), bulbar function (n = 16), arm function (n = 65), respiration (n = 15), trunk function (n = 34), leg function (n = 76) and generalized symptoms (n = 77). Median symptom severity decreased during nusinersen treatment (median observational period 6.1 months, 0.5–16 months) from 3.7 to 3.3 MYMOP2 score points (p < 0.001). The convenience of drug administration was critical (49.7 of 100 TSQM-9 points, SD 22); however, the overall treatment satisfaction was high (74.3, SD 18) and the recommendation rating very positive (NPS +66). Conclusions Nusinersen was administered across a broad range of ages, disease durations and motor function deficits. Treatment expectations were highly differentiated and related to SMA type and functional status. Patient-reported outcomes demonstrated a positive perception of nusinersen therapy in adult patients with 5q-SMA., publishedVersion
- Published
- 2021
5. Complications, outcome and owner satisfaction after Callicrate Bander phallectomy and perineal urethrostomy in 14 equids
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T. Maurer, H. P. Brünisholz, T. O'Brien, M. Coleridge, M. D. Klopfenstein‐Bregger, and C. Koch
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630 Agriculture ,Equine - Published
- 2022
6. Loss‐of‐Function Variants in <scp>HOPS</scp> Complex Genes <scp> VPS16 </scp> and <scp> VPS41 </scp> Cause Early Onset Dystonia Associated with Lysosomal Abnormalities
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Manju A. Kurian, Joanna M. Flowers, Kishore R. Kumar, Glenn Anderson, Sniya Sudhakar, Matej Skorvanek, Bernhard Haslinger, Kshitij Mankad, Martje E. van Egmond, Corien Verschuuren, Rauan Kaiyrzhanov, Nicholas W. Wood, Arianna Ferrini, Nardo Nardocci, Riccardo Berutti, Arcangela Iuso, Barbara Plecko, Juliane Winkelmann, Matias Wagner, P. Darveniza, Philippe Coubes, Arianna Tucci, Paulina Gonzalez-Latapi, Ryan L. Davis, Diane Demailly, Katy Barwick, Erik-Jan Kamsteeg, Kai Bötzel, Tomasz Kmieć, Ján Necpál, Giovanna Zorzi, Derek Burke, Sylvia Boesch, Dora Steel, Barbara Garavaglia, Steven J. Lubbe, Bernabé I. Bustos, Carolyn M. Sue, Chen Zhao, Meriel McEntagart, Stephen Tisch, Henry Houlden, Jan C. Koch, Robert Jech, Sarah Wiethoff, Michael Zech, Laura Cif, Niccolo E. Mencacci, Marina A. J. Tijssen, Suvasini Sharma, Kathryn J. Peall, Paul Gissen, and Kathleen M. Gorman
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0301 basic medicine ,Genetics ,Dystonia ,Protein subunit ,Biology ,medicine.disease ,Phenotype ,3. Good health ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Genetic variation ,Etiology ,medicine ,Neurology (clinical) ,Gene ,030217 neurology & neurosurgery ,Loss function - Abstract
Objectives The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognised. We aimed to investigate this paucity of diagnoses. Methods We undertook weighted burden analysis of whole‐exome sequencing data from 138 individuals with unresolved generalised dystonia of suspected genetic aetiology, followed by additional case‐finding from international databases, first for the gene implicated by the burden analysis (VPS16), then for other functionally related genes. Electron microscopy was performed on patient‐derived cells. Results Analysis revealed a significant burden for VPS16 (Fisher's exact test p‐value, 6.9x10−9). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome‐lysosome fusion. A total of 18 individuals harbouring heterozygous loss‐of‐function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early‐onset progressive dystonia with predominant cervical, bulbar, orofacial and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss‐of‐function variants in VPS41, another HOPS‐complex encoding genes, in an individual with infantile‐onset generalised dystonia. Electron microscopy of patient‐derived lymphocytes and fibroblasts from both VPS16 and VPS41 patients showed vacuolar abnormalities suggestive of impaired lysosomal function. Interpretation Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, though variants in different subunits display different phenotypic and inheritance characteristics.
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- 2020
7. Mysterious syndrome causing high mortality in wild brown trout in Eastern Switzerland, pathology and search for a possible cause
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Michel C. Koch, Michael Kugler, Heike Schmidt-Posthaus, Christoph Birrer, Regula Hirschi, and Torsten Seuberlich
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0301 basic medicine ,endocrine system ,Viral metagenomics ,Pathology ,medicine.medical_specialty ,animal structures ,Trout ,animal diseases ,Veterinary (miscellaneous) ,Aquatic Science ,Biology ,Population density ,Fish Diseases ,03 medical and health sciences ,Brown trout ,Rivers ,medicine ,Animals ,Salmo ,Hepatitis ,630 Agriculture ,urogenital system ,Myocardium ,High mortality ,High-Throughput Nucleotide Sequencing ,04 agricultural and veterinary sciences ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Liver ,Oncorhynchus mykiss ,040102 fisheries ,Etiology ,0401 agriculture, forestry, and fisheries ,Rainbow trout ,Metagenomics ,Switzerland - Abstract
Since 2016, annually occurring species- specific die-offs of brown trout (Salmo trutta fario) occurred in the Thur river, situated in the Eastern part of Switzerland. These events lead to drastically reduced population densities in the impacted river regions. Clinical signs in brown trout and mortality were restricted to few weeks in August / September. To characterize the syndrome and to find possible causes, from end of March to November 2018, one year old brown trout (Salmo trutta fario) and rainbow trout (Oncorhynchus mykiss) were exposed to water from Thur river, fish were sampled regularly and screened for infectious agents, including viral metagenomics, and pathology was described. Starting approximately four months post exposure, brown trout showed severe lymphohistiocytic pancarditis and necrotising and haemorrhagic hepatitis. These lesions were recorded until the end of the experiment in November. Rainbow trout were not affected at any point in time. No infectious agents could be identified so far as cause of disease, especially no viral aetiology. Even if pathogenesis and pathology points in the direction of an infectious agent, a causative relationship could not be confirmed and aetiology remains unclear.
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- 2020
8. Rho‐kinase inhibition by fasudil modulates pre‐synaptic vesicle dynamics
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Mathias Bähr, Anna-Elisa Roser, Kim Ann Saal, Paul Lingor, Jan C. Koch, Carmina Warth Perez Arias, and Silvio O. Rizzoli
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Male ,0301 basic medicine ,Presynaptic Terminals ,Stimulation ,Neurotransmission ,Hippocampus ,Synaptic Transmission ,Biochemistry ,Synaptic vesicle ,Synapse ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,medicine ,Animals ,Rats, Wistar ,Protein Kinase Inhibitors ,Rho-associated protein kinase ,Neurons ,rho-Associated Kinases ,Chemistry ,Neurodegeneration ,Fasudil ,medicine.disease ,Rats ,3. Good health ,Cell biology ,ddc ,030104 developmental biology ,Female ,Synaptic Vesicles ,Signal transduction ,030217 neurology & neurosurgery - Abstract
The Rho kinase (ROCK) signaling pathway is an attractive therapeutic target in neurodegeneration since it has been linked to the prevention of neuronal death and neurite regeneration. The isoquinoline derivative fasudil is a potent ROCK inhibitor, which is already approved for chronic clinical treatment in humans. However, the effects of chronic fasudil treatments on neuronal function are still unknown. We analyzed here chronic fasudil treatment in primary rat hippocampal cultures. Neurons were stimulated with 20 Hz field stimulation and we investigated pre-synaptic mechanisms and parameters regulating synaptic transmission after fasudil treatment by super resolution stimulated emission depletion (STED) microscopy, live-cell fluorescence imaging, and western blotting. Fasudil did not affect basic synaptic function or the amount of several synaptic proteins, but it altered the chronic dynamics of the synaptic vesicles. Fasudil reduced the proportion of the actively recycling vesicles, and shortened the vesicle lifetime, resulting overall in a reduction of the synaptic response upon stimulation. We conclude that fasudil does not alter synaptic structure, accelerates vesicle turnover, and decreases the number of released vesicles. This broadens the known spectrum of effects of this drug, and suggests new potential clinical uses.
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- 2020
9. Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix
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Matthias W. Beckmann, Melanie Boxberg, Aurelia Noske, Katja Steiger, Adrian Wenzel, Martin C. Koch, Frido Brühl, Johanna D Strehl, Anna Melissa Schlitter, Grit Mehlhorn, Andreas Schnelzer, Wilko Weichert, Arne Warth, Marion Kiechle, Arndt Hartmann, Björn Konukiewitz, and Moritz Jesinghaus
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Oncology ,medicine.medical_specialty ,Lung ,business.industry ,Cell ,Hazard ratio ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Uterine cervix ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,030221 ophthalmology & optometry ,medicine ,Tumour budding ,Basal cell ,business ,Grading (tumors) - Abstract
A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity.
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- 2018
10. Band-tailed pigeon use of supplemental mineral
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Ryan C. Koch and Todd A. Sanders
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0106 biological sciences ,chemistry.chemical_classification ,Mineral ,Ecology ,biology ,Sodium ,Salt (chemistry) ,chemistry.chemical_element ,Calcium ,biology.organism_classification ,01 natural sciences ,010605 ornithology ,010601 ecology ,Geography ,Animal science ,chemistry ,Patagioenas fasciata ,General Earth and Planetary Sciences ,Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation ,General Environmental Science - Published
- 2017
11. Tracer-based evidence of heterogeneity in subsurface flow and storage within a boreal hillslope
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Donald M. Reeves, Joshua C. Koch, and Ryan C. Toohey
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010504 meteorology & atmospheric sciences ,0208 environmental biotechnology ,Taiga ,Soil science ,02 engineering and technology ,STREAMS ,Permafrost ,Preferential flow ,01 natural sciences ,020801 environmental engineering ,Boreal ,TRACER ,Subsurface flow ,Surface runoff ,Geomorphology ,Geology ,0105 earth and related environmental sciences ,Water Science and Technology - Published
- 2017
12. Lateral and subsurface flows impact arctic coastal plain lake water budgets
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Joshua C. Koch
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Hydrology ,010504 meteorology & atmospheric sciences ,Water flow ,0208 environmental biotechnology ,02 engineering and technology ,Permafrost ,01 natural sciences ,020801 environmental engineering ,Hydrology (agriculture) ,Arctic ,Evapotranspiration ,Subsurface flow ,Surface runoff ,Surface water ,Geology ,0105 earth and related environmental sciences ,Water Science and Technology - Abstract
Arctic thaw lakes are an important source of water for aquatic ecosystems, wildlife, and humans. Many recent studies have observed changes in Arctic surface waters related to climate warming and permafrost thaw; however, explaining the trends and predicting future responses to warming is difficult without a stronger fundamental understanding of Arctic lake water budgets. By measuring and simulating surface and subsurface hydrologic fluxes, this work quantified the water budgets of three lakes with varying levels of seasonal drainage, and tested the hypothesis that lateral and subsurface flows are a major component of the post‐snowmelt water budgets. A water budget focused only on post‐snowmelt surface water fluxes (stream discharge, precipitation, and evaporation) could not close the budget for two of three lakes, even when uncertainty in input parameters was rigorously considered using a Monte Carlo approach. The water budgets indicated large, positive residuals, consistent with up to 70% of mid‐summer inflows entering lakes from lateral fluxes. Lateral inflows and outflows were simulated based on three processes; supra‐permafrost subsurface inflows from basin‐edge polygonal ground, and exchange between seasonally drained lakes and their drained margins through runoff and evapotranspiration. Measurements and simulations indicate that rapid subsurface flow through highly conductive flowpaths in the polygonal ground can explain the majority of the inflow. Drained lakes were hydrologically connected to marshy areas on the lake margins, receiving water from runoff following precipitation and losing up to 38% of lake efflux to drained margin evapotranspiration. Lateral fluxes can be a major part of Arctic thaw lake water budgets and a major control on summertime lake water levels. Incorporating these dynamics into models will improve our ability to predict lake volume changes, solute fluxes, and habitat availability in the changing Arctic. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
- Published
- 2016
13. Surface water connectivity drives richness and composition of Arctic lake fish assemblages
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Trevor B. Haynes, Amanda E. Rosenberger, Christian E. Zimmerman, Joshua C. Koch, Matthew S. Whitman, Mark S. Wipfli, and Sarah M. Laske
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0106 biological sciences ,geography ,geography.geographical_feature_category ,Occupancy ,Ecology ,Coastal plain ,010604 marine biology & hydrobiology ,Ephemeral key ,Body size and species richness ,15. Life on land ,Aquatic Science ,Biology ,010603 evolutionary biology ,01 natural sciences ,Colonisation ,Arctic ,13. Climate action ,14. Life underwater ,Species richness ,Surface water - Abstract
Summary Surface water connectivity can influence the richness and composition of fish assemblages, particularly in harsh environments where colonisation factors and access to seasonal refugia are required for species persistence. Studies regarding influence of connectivity on Arctic fish distributions are limited and are rarely applied to whole assemblage patterns. To increase our understanding of how surface water connectivity and related hydrologic variables influence assemblage patterns, we investigated species richness and composition of Arctic lake fishes over a large region, 8500 km2, of the central Arctic Coastal Plain, Alaska. We collected fish presence/non-detection data from 102 lakes and used a hierarchical multispecies occupancy framework to derive species richness and inform species composition patterns. Our mean estimate of regional richness was 12.3 (SD 0.5) species. Presence of a permanent channel connection was an overriding factor affecting species richness (mean 3.6, 95% CI 3.1–4.9), presumably driving lake colonisation potential. In lakes without a permanent channel connection, data suggest richness (mean 2.0, 95% CI 1.7–3.3) increased with the availability of in-lake winter refugia and with the potential of ephemeral connections during spring floods. Fish species functional traits and environmental faunal filters contributed to patterns of richness and assemblage composition. Composition corresponded with richness in a coherent manner, where each successive level of richness contained several discrete assemblages that showed similar responses to the environment. Lakes with permanent channel connections contained both widespread and restricted species, while the species-poor lakes that lacked a connection contained mainly widespread species. This work provides useful baseline information on the processes that drive the relations between patch connectivity and fish species richness and assemblage composition. The environmental processes that organise fish assemblages in Arctic lakes are likely to change in a warming climate.
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- 2016
14. Comparative nest survival of three sympatric loon species breeding in the Arctic
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Joshua C. Koch, Kenneth G. Wright, Brian D. Uher-Koch, and Joel A. Schmutz
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0106 biological sciences ,Nest ,Sympatric speciation ,Ecology ,Animal Science and Zoology ,Biology ,010603 evolutionary biology ,01 natural sciences ,Ecology, Evolution, Behavior and Systematics ,010605 ornithology ,The arctic - Published
- 2018
15. AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury
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Hans Werner Müller, Frank Bradke, Malleswari Challagundla, Thomas Ostendorf, Uwe Michel, Vinicius Toledo Ribas, Mathias Bähr, Sebastian Kügler, Paul Lingor, and Jan C. Koch
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Pathology ,ROCK2 protein, rat ,Red nucleus ,Biochemistry ,0302 clinical medicine ,pathology [Red Nucleus] ,pathology [Neurons] ,ROCK2 ,RNA, Small Interfering ,Spinal cord injury ,biosynthesis [rho-Associated Kinases] ,Red Nucleus ,Neurons ,rho-Associated Kinases ,0303 health sciences ,Dependovirus ,genetics [Transcription Factors] ,Immunohistochemistry ,3. Good health ,DNA-Binding Proteins ,genetics [rho-Associated Kinases] ,medicine.anatomical_structure ,Female ,biosynthesis [DNA-Binding Proteins] ,pathology [Spinal Cord Injuries] ,medicine.symptom ,medicine.medical_specialty ,Cell Survival ,Blotting, Western ,Genetic Vectors ,Molecular Sequence Data ,genetics [DNA-Binding Proteins] ,Biology ,biosynthesis [Transcription Factors] ,BAG1 ,Lesion ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Atrophy ,methods [Genetic Therapy] ,medicine ,Animals ,ddc:610 ,Rats, Wistar ,Spinal Cord Injuries ,030304 developmental biology ,Base Sequence ,Genetic Therapy ,Recovery of Function ,medicine.disease ,Spinal cord ,Axons ,Nerve Regeneration ,Rats ,Disease Models, Animal ,physiology [Nerve Regeneration] ,BCL2-associated athanogene 1 protein ,Neuroscience ,030217 neurology & neurosurgery ,Rubrospinal tract ,Transcription Factors - Abstract
A lesion to the rat rubrospinal tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the rubrospinal tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the rubrospinal tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion.
- Published
- 2015
16. Risk Factors for Survival in a University Hospital Population of Dogs with Epilepsy
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Mette Berendt, B. C. Koch, Nils Toft, and N. Fredso
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Male ,medicine.medical_specialty ,Poor prognosis ,Population ,Life span ,Standard Article ,Neurological disorder ,Canine ,Hospitals, University ,Hospitals, Animal ,Epilepsy ,Dogs ,Risk Factors ,Internal medicine ,medicine ,Animals ,Dog Diseases ,Mortality ,education ,Intact male ,Retrospective Studies ,Cause of death ,education.field_of_study ,General Veterinary ,business.industry ,medicine.disease ,University hospital ,Survival Analysis ,Seizure ,Standard Articles ,Surgery ,Epilepsy, Generalized ,Female ,Epilepsies, Partial ,business - Abstract
Background Although a common neurological disorder in dogs, long-term outcome of epilepsy is sparsely documented. Objectives To investigate risk factors for survival and duration of survival in a population of dogs with idiopathic epilepsy or epilepsy associated with a known intracranial cause. Animals One hundred and two client owned dogs; 78 dogs with idiopathic epilepsy and 24 dogs with epilepsy associated with a known intracranial cause. Methods A retrospective hospital based study with follow-up. Dogs diagnosed with epilepsy between 2002 and 2008 were enrolled in the study. Owners were interviewed by telephone using a structured questionnaire addressing epilepsy status, treatment, death/alive, and cause of death. Results Median life span was 7.6 years, 9.2 years, and 5.8 years for all dogs, and dogs with idiopathic epilepsy or dogs with epilepsy associated with a known intracranial cause (P
- Published
- 2014
17. Early and Sustained Activation of Autophagy in Degenerating Axons after Spinal Cord Injury
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Jan C. Koch, Paul Lingor, Vinicius Toledo Ribas, Bianca Schnepf, Malleswari Challagundla, and Mathias Bähr
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Autophagosome ,Pathology ,medicine.medical_specialty ,General Neuroscience ,ATG5 ,Autophagy ,Central nervous system ,Biology ,ULK1 ,medicine.disease ,3. Good health ,Pathology and Forensic Medicine ,Lesion ,medicine.anatomical_structure ,nervous system ,medicine ,Neurology (clinical) ,Axon ,medicine.symptom ,Neuroscience ,Spinal cord injury - Abstract
Axonal degeneration is one of the initial steps in many neurological disorders and has been associated with increased autophagic activity. Although there are increasing data on the regulation of autophagy proteins in the neuronal soma after spinal cord injury (SCI), their characterization in the axon is scarce. Here, we examined the regulation of autophagy during axonal degeneration in a rat model of SCI following a lesion at Th 8. We analyzed the morphological and ultrastructural changes in injured axons by immunohistochemical evaluation of autophagy-related proteins and electron microscopy at different time points following SCI. The expression of ULK1, Atg7 and Atg5 in damaged axons was rapidly upregulated within hours after SCI. The number of axonal LC3-positive autophagosomes was also rapidly increased after SCI and remained at an increased level for up to 6 weeks. Ultrastructural analysis showed early signs of axonal degeneration and increased autophagy. In conclusion, we show that autophagy is increased early and for a sustained period in degenerating axons after SCI and that it might be an important executive step involved in axonal degeneration. Therefore, autophagy may represent a promising target for future therapeutic interventions in the treatment of axonal degeneration in traumatic central nervous system disorders.
- Published
- 2014
18. Morphology-Dependent Water Budgets and Nutrient Fluxes in Arctic Thaw Ponds
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Kirsty E. B. Gurney, Joshua C. Koch, and Mark S. Wipfli
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Hydrology ,geography ,geography.geographical_feature_category ,Coastal plain ,Phosphorus ,fungi ,chemistry.chemical_element ,Permafrost ,Nutrient ,Oceanography ,Habitat ,Productivity (ecology) ,chemistry ,Arctic ,parasitic diseases ,Ecosystem ,Geology ,Earth-Surface Processes - Abstract
Thaw ponds on the Arctic Coastal Plain of Alaska are productive ecosystems, providing habitat and food resources for many fish and bird species. Permafrost in this region creates unique pond morphologies: deep troughs, shallow low-centred polygons (LCPs) and larger coalescent ponds. By monitoring seasonal trends in pond volume and chemistry, we evaluated whether pond morphology and size affect water temperature and desiccation, and nitrogen (N) and phosphorus (P) fluxes. Evaporation was the largest early-summer water flux in all pond types. LCPs dried quickly and displayed high early-summer nutrient concentrations and losses. Troughs consistently received solute-rich subsurface inflows, which accounted for 12 to 42 per cent of their volume and may explain higher P in the troughs. N to P ratios increased and ammonium concentrations decreased with pond volume, suggesting that P and inorganic N availability may limit ecosystem productivity in older, larger ponds. Arctic summer temperatures will likely increase in the future, which may accelerate mid-summer desiccation. Given their morphology, troughs may remain wet, become warmer and derive greater nutrient loads from their thawing banks. Overall, seasonal- to decadal-scale warming may increase ecosystem productivity in troughs relative to other Arctic Coastal Plain ponds. Copyright © 2014 John Wiley & Sons, Ltd.
- Published
- 2014
19. Plasmids containing NRSE/RE1 sites enhance neurite outgrowth of retinal ganglion cells via sequestration of REST independent of NRSE dsRNA expression
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Elisabeth Barski, Mathias Bähr, Uwe Michel, Jan C. Koch, and Paul Lingor
- Subjects
Neurite ,HEK 293 cells ,Repressor ,Cell Biology ,Transfection ,Biology ,Biochemistry ,Molecular biology ,Retinal ganglion ,medicine.anatomical_structure ,Retinal ganglion cell ,medicine ,Gene silencing ,Molecular Biology ,Transcription factor - Abstract
Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor of neuron-specific genes that binds to a conserved DNA element, the neuron restrictive silencer element (NRSE/RE1). Interestingly, increased REST activity is found in several neurological diseases like Huntington's disease and cerebral ischemia. Recently, it was shown that NRSE dsRNA, a double-stranded non-coding RNA can bind to REST during a defined period of neuronal differentiation, and thereby changes REST from a transcriptional repressor to an activator of neuron-specific genes. Here, we analyzed the effects of NRSE dsRNA expression in primary retinal ganglion cells. We found that NRSE dsRNA expression vectors significantly enhance neurite outgrowth even when axonal degeneration is induced by neurotrophin deprivation. Transfection of HEK cells with NRSE dsRNA-expressing vectors altered their morphology leading to the formation of thin processes and induced the expression of neurofilament-68. Surprisingly, control vectors containing REST-binding sites, but not expressing NRSE dsRNA, resulted in the same effects, also in the retinal ganglion cell model. Reporter assays and retention of REST in the cytoplasm with a labeled NRSE/RE1-containing plasmid incapable of entering the nucleus suggest that sequestration of REST in the cytoplasm is the reason for the observed effects. No evidence for a biological function of NRSE dsRNA could be found in these models. We conclude that sequestration of REST leads to enhanced neurite outgrowth in retinal ganglion cells and that an increased activity of REST, as it is found in several neurodegenerative diseases, can be effectively modulated by sequestration of REST with plasmids containing NRSE/RE1 sites.
- Published
- 2011
20. Reversible Addition-Fragmentation Chain Transfer Polymerization Implemented as Continuous Process in CSTR and PFR at Elevated Reaction Conditions
- Author
-
Sara C. Koch and Markus Busch
- Subjects
Kinetic chain length ,Materials science ,General Chemical Engineering ,Radical polymerization ,Chain transfer ,General Chemistry ,Industrial and Manufacturing Engineering ,Chain-growth polymerization ,Polymerization ,Chemical engineering ,Polymer chemistry ,Precipitation polymerization ,Living polymerization ,Reversible addition−fragmentation chain-transfer polymerization - Abstract
The reversible addition-fragmentation chain transfer polymerization is a very versatile type of polymerization to produce (co)polymers of well-defined structure. However, in most cases this process has not exceeded the status of laboratory scale. Besides the major interest in developing well-defined polymer structures in the first row, the relative low speed of polymerization may be another argument. Elevated temperature and pressure may be an option to increase the rate of polymerization to a significant level. The presented work will test for this and inspect the potential of implementing this type of polymerization into a continuous process. On a micro-plant scale, this might be attractive to generate reasonable quantities of well-defined (co)polymers showing low polydispersity indices.
- Published
- 2011
21. A synthesis of oxytocin
- Author
-
J. S. Bontekoe, A. C. Koch, and H. C. Beyerman
- Subjects
chemistry.chemical_compound ,Oxytocin ,Chemistry ,Stereochemistry ,Amide ,Pituitary hormones ,medicine ,General Chemistry ,medicine.drug - Abstract
The synthesis is described of the “protected” linear nonapeptide: N-benzyloxycarbonyl-S-benzyl-L-cysteinyl-L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycine amide (XI). In the new reaction steps N,N′-dicyclohexylcarbodiimide was used as sole coupling agent in combination with a variety of blocking groups. The conversion of XI into the pituitary hormone oxytocin is known.
- Published
- 2010
22. The changing balance of brainstem-spinal cord modulation of pain processing over the first weeks of rat postnatal life
- Author
-
Lucie A. Low, Maria Fitzgerald, Stephanie C. Koch, and Gareth J. Hathway
- Subjects
Physiology ,Chronic pain ,medicine.disease ,Spinal cord ,Nociceptive flexion reflex ,Nociception ,medicine.anatomical_structure ,Anesthesia ,Hyperalgesia ,medicine ,Reflex ,Rostral ventromedial medulla ,Brainstem ,medicine.symptom ,Psychology ,Neuroscience - Abstract
Brainstem–spinal cord connections play an essential role in adult pain processing, and the modulation of spinal pain network excitability by brainstem nuclei is known to contribute to hyperalgesia and chronic pain. Less well understood is the role of descending brainstem pathways in young animals when pain networks are more excitable and exposure to injury and stress can lead to permanent modulation of pain processing. Here we show that up to postnatal day 21 (P21) in the rat, the rostroventral medulla of the brainstem (RVM) exclusively facilitates spinal pain transmission but that after this age (P28 to adult), the influence of the RVM shifts to biphasic facilitation and inhibition. Graded electrical microstimulation of the RVM at different postnatal ages revealed a robust shift in the balance of descending control of both spinal nociceptive flexion reflex EMG activity and individual dorsal horn neuron firing properties, from excitation to inhibition, beginning after P21. The shift in polarity of descending control was also observed following excitotoxic lesions of the RVM in adult and P21 rats. In adults, RVM lesions decreased behavioural mechanical sensory reflex thresholds, whereas the same lesion in P21 rats increased thresholds. These data demonstrate, for the first time, the changing postnatal influence of the RVM in spinal nociception and highlight the central role of descending brainstem control in the maturation of pain processing.
- Published
- 2009
23. Association of arytenoid chondritis with equine lymphocyte antigens but no association with laryngeal hemiplegia, umbilical hernias and cryptorchidism
- Author
-
C. Koch, J. J. McCLURE, J. R. McCLURE, and M. Powell
- Subjects
Male ,Larynx ,medicine.medical_specialty ,Biology ,Gastroenterology ,Gene Frequency ,Species Specificity ,Histocompatibility Antigens ,Internal medicine ,Cryptorchidism ,Genetics ,Paralysis ,medicine ,Animals ,Horses ,Lymphocytes ,Vocal cord paralysis ,Horse ,Arytenoid cartilage ,General Medicine ,Anatomy ,medicine.disease ,Antigens, Differentiation ,Histocompatibility ,Umbilical hernia ,medicine.anatomical_structure ,Relative risk ,Female ,Horse Diseases ,Animal Science and Zoology ,medicine.symptom ,Cartilage Diseases ,Vocal Cord Paralysis ,Hernia, Umbilical ,Arytenoid Cartilage - Abstract
Associations were sought between ELA A1-A10 and W11 antigens and the presence of laryngeal hemiplegia, arytenoid chondritis, umbilical hernias and cryptorchidism in Thoroughbreds and/or Quarter Horses. No significant associations were detected between laryngeal hemiplegia and any ELA antigen in Thoroughbreds. The association between arytenoid chondritis and A9 was significant with a relative risk (RR) of 15.6 and aetiologic fraction (EF) of 0.80 in Thoroughbreds. There were apparent associations based on RR between A4 and A5 in Quarter Horses with umbilical hernias (RR = 7.5 and 6.1 respectively); however, these were not statistically significant. No significant associations were detected with cryptorchidism in Quarter Horses when the control population included both sexes. When only unaffected males were used as the control group, there was an apparent increase in relative risk with A6 (from RR = 1.7 to 4.3); however this was not statistically significant. Cryptorchidism in Thoroughbreds showed an increased relative risk with A5 regardless of whether the control population included males and females (RR = 4.1) or only males (RR = 4.7) but the increases were not statistically significant.
- Published
- 2009
24. THE TENEBRIONIDAE OF SOUTHERN AFRICA. XI: NEW EPITRAGINI AND CRYPTOCHILINI FROM THE BRITISH MUSEUM
- Author
-
C. Koch
- Subjects
Geography ,Insect Science ,Ancient history ,Archaeology ,Ecology, Evolution, Behavior and Systematics - Published
- 2009
25. Genetic Control of Antibody Responses to PHA in Inbred Rats
- Author
-
C. Koch
- Subjects
High responder ,Genetic Linkage ,Immunology ,chemical and pharmacologic phenomena ,Biology ,Major histocompatibility complex ,Antibodies ,Species Specificity ,Antigen ,Histocompatibility Antigens ,Lectins ,Rats, Inbred BN ,Animals ,Lymphocytes ,Crosses, Genetic ,Rats, Inbred Strains ,General Medicine ,Molecular biology ,In vitro ,Low responder ,Rats ,Antibody response ,Genes ,Antibody Formation ,biology.protein ,Female - Abstract
Phytohemagglutinin (PHA-P; Difco) contains four immunogenic components. The antibody response in rats to two of these components is shown to be genetically determined: AS rats are high responders and BN rats are low responders to both antigens. Responsiveness to the two components segregates independently as autosomal, dominant traits in a manner that is compatible with a one-gene hypothesis for both responses. The antibody response to the mitogenic fraction of PHA segregates together with the in vitro mitogenic response to PHA and to other mitogens. These responses are not linked to the major histocompatibility complex (MHC) of the rat. The antibody response to a nonmitogenic fraction from PHA is, however, linked to the MHC.
- Published
- 2008
26. Studienergebnisse der entomologischen Expeditionen Seiner Durchlaucht des Fürsten della Torre e Tasso in Nordafrika und Sizilien
- Author
-
C. Koch
- Subjects
Insect Science - Published
- 2008
27. Determination of Activation Volume in Nanocrystalline Cu Using the Shear Punch Test
- Author
-
Kris A. Darling, Ronald O. Scattergood, Ramesh K. Guduru, Carl C. Koch, Korukonda L. Murty, and P.Z. Wong
- Subjects
Materials science ,Deformation mechanism ,Stress relaxation ,Mineralogy ,von Mises yield criterion ,General Materials Science ,Direct shear test ,Plasticity ,Pure shear ,Deformation (meteorology) ,Composite material ,Condensed Matter Physics ,Tensile testing - Abstract
The mechanical behavior of nanocrystalline metals has been a research topic of interest for the past two decades. The current understanding is summarized in several recent reviews. Researchers have been investigating the deformation mechanisms in nanocrystalline metals and alloys through experimental and modeling routes. Modeling results indicate that there is a transition from dislocation generation at sources within grains to grain-boundary mediated dislocation generation in the grain size range between about 100 to 10 nm. Below 10 nm, grain boundary deformation modes (sliding, rotation, etc.) become dominant and inverse Hall-Petch effects have been reported. Experimental evidence to confirm these predictions is an active area of research. Two important experimental parameters that are useful in characterizing the deformation kinetics of materials are the strain rate sensitivity m and the activation volume V*. 11, 12] These are related by m = kT/V*r where k is Boltzmann’s constant, T is temperature (K) and r is the stress. There is a limited amount of data available on m and V* measurements for nanocrystalline metals. 5, 11–14] One aspect of this is the fact that research-scale synthesizing techniques often produce small quantities of material and mechanical testing procedures suited to small sample sizes are required. 5, 7, 13–18] In addition to this fact there is a tremendous scarcity of testing methodologies for testing the materials at small scales such as Micro-Electro-Mechanical-Systems (MEMS) where micro tensile and nanoindentation tests are used for understanding the deformation behaviour. 20] The aim of the present work was to extend the shear punch test (SPT) technique to the measurement of activation volumes on small scale specimens of few millimeters (∼ 1 mm to 3 mm). The advantage of SPT over nanoindentation and micro tensile tests is the deformation zone where a large number of grains undergo deformation within the shear zone and overcomes the problem of strain gradient plasticity effects, gain size effects as well as the specimen size effects. The SPT has been used for evaluating the yield and ultimate stress by numerous researchers, including us. The SPT shear yield or ultimate strength value s can be correlated with its tensile test counterpart r using the relation r = as. The correlation factor a depends upon the testing setup and data analysis methods. The Von Mises (VM) yield criterion predicts a = 3 if the SPT approximates pure shear loading conditions. This was the case in where the details and standardization of the SPT technique used in the present research work are given. The stress relaxation method has been used to determine activation volumes and dislocation dynamics in coarse-grain metals and alloys and in nanocrystalline Ni. The tests are normally done using uniaxial loading conditions. In the present study, we use the stress relaxation method in conjunction with the SPT technique. As far as we are aware, this is the first time that the full implementation of this method has been reported.
- Published
- 2007
28. Wie verlässlich sind aktuelle Docking-Ansätze für strukturbasiertes Wirkstoffdesign? – Fallstudie zur Aldose-Reduktase
- Author
-
Holger Steuber, Concettina La Motta, Christoph A. Sotriffer, C. Koch, Gerhard Klebe, Matthias Zentgraf, and Stefania Sartini
- Subjects
Chemistry ,General Medicine - Published
- 2007
29. How Reliable Are Current Docking Approaches for Structure-Based Drug Design? Lessons from Aldose Reductase
- Author
-
Stefania Sartini, Gerhard Klebe, Holger Steuber, Matthias Zentgraf, C. Koch, Concettina La Motta, and Christoph A. Sotriffer
- Subjects
Drug ,Aldose reductase ,Binding Sites ,Databases, Factual ,Chemistry ,media_common.quotation_subject ,General Chemistry ,Computational biology ,Aldose reductase inhibitors ,Crystallography, X-Ray ,Ligands ,Catalysis ,Structure-Activity Relationship ,Biochemistry ,Aldehyde Reductase ,Docking (molecular) ,Drug Design ,Structure based ,Computer Simulation ,Enzyme Inhibitors ,media_common - Published
- 2007
30. Thickness and Clearance Effects in Shear Punch Testing
- Author
-
Ronald O. Scattergood, Korukonda L. Murty, A.V. Nagasekhar, Ramesh K. Guduru, and Carl C. Koch
- Subjects
Materials science ,business.industry ,Martensitic stainless steel ,Structural engineering ,Plasticity ,engineering.material ,Condensed Matter Physics ,Finite element method ,Brass ,Shear (sheet metal) ,visual_art ,Ultimate tensile strength ,visual_art.visual_art_medium ,engineering ,General Materials Science ,business - Abstract
Shear punch testing (SPT) is a miniaturized specimen testing technique and is often used to predict the tensile properties of metals and alloys by testing a small amount of material. In order to rationalize the testing methodology it is necessary to understand the effect of different testing procedure parameters such as specimen thickness and die-punch clearance on the evaluated mechanical properties. We present our understanding of the above parameters on the SPT yield strength using finite element modeling studies in conjunction with our previous experimental results.
- Published
- 2007
31. Iatrogenic secondary hypoadrenocorticism in a horse with pituitary pars intermedia dysfunction (equine Cushing's disease)
- Author
-
M. T. Donaldson, James A. Orsini, C. Koch, and R. Boswell
- Subjects
medicine.medical_specialty ,Equine ,business.industry ,medicine.medical_treatment ,Horse ,medicine.disease ,Endocrinology ,Secondary hypoadrenocorticism ,Boldenone undecylenate ,Internal medicine ,Addison's disease ,Adrenal insufficiency ,medicine ,Pituitary pars intermedia dysfunction ,business ,Anabolic steroid ,Stanozolol ,medicine.drug - Published
- 2007
32. Secular changes in anthropometric data in cystic fibrosis patients
- Author
-
Jørgen Holm Petersen, C Koch, J Müller, and EM Laursen
- Subjects
Selection bias ,medicine.medical_specialty ,Anthropometric data ,business.industry ,media_common.quotation_subject ,General Medicine ,Anthropometry ,medicine.disease ,Cystic fibrosis ,Endocrinology ,El Niño ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Severity of illness ,Epidemiology ,Medicine ,sense organs ,skin and connective tissue diseases ,business ,Body mass index ,Demography ,media_common - Abstract
The aim of this study was to study the secular changes in anthropometric data over calendar time in patients with cystic fibrosis (CF). Growth curves were constructed for 270 patients based on height and weight registrations from the medical files. Height, body mass index (BMI), magnitude of pubertal peak height velocity (PHV) and age at PHV were analysed for possible secular changes from the 1960s to the 1990s. There was a significant change in height over calendar time in only 1 of 12 age groups. BMI showed a significant increase in 10- and 15-y-old boys and girls and in 5-y-old girls. The magnitude of PHV changed significantly over time, whereas age at PHV was constant. No significant changes in height and age at PHV over calendar time were observed; this was probably due to a selection bias since the oldest patients, who survived to be part of the present investigation, represented milder forms of the disease. The increase in BMI and change in magnitude of PHV over calendar time may reflect the improvement in treatment leading to a better survival and clinical status through puberty. The increase in BMI and change in magnitude of PHV were sufficient to overcome the selection bias from older patients with milder disease.
- Published
- 2007
33. Comment: Middle Pleistocene sedimentation at Pakefield, Suffolk, England. J. R. Lee, J. Rose, I. Candy and R. W. Barendregt (2006). Journal of Quaternary Science 21: 155–1791
- Author
-
H. W. Bailey, Colin A. Whiteman, C. Koch, P.L. Gibbard, John E. Whittaker, Steve Boreham, Andrea Moscariello, and A. R. Lord
- Subjects
Rose (mathematics) ,Geography ,Arts and Humanities (miscellaneous) ,Pleistocene ,Earth and Planetary Sciences (miscellaneous) ,Quaternary science ,Paleontology ,Sedimentation ,Archaeology - Published
- 2007
34. Genetic heterogeneity of synpolydactyly: a novel locus SPD3 maps to chromosome 14q11.2-q12
- Author
-
Sajid Malik, Amir Ali Abbasi, Manuela C. Koch, Muhammad Ansar, Wasim Ahmad, and Karl-Heinz Grzeschik
- Subjects
Genetics ,Genetic heterogeneity ,Haplotype ,Locus (genetics) ,Biology ,medicine.disease ,Penetrance ,Synpolydactyly ,Gene mapping ,HOXD13 ,medicine ,Syndactyly ,Genetics (clinical) - Abstract
Syndactyly type II or synpolydactyly (SPD) is the second most frequent syndactyly type and is inherited in an autosomal dominant fashion. The cardinal features of this malformation are the cutaneous or bony fusion of third and fourth fingers, and fourth and fifth toes associated with additional digital elements within the web. It shows incomplete penetrance and high inter- and intrafamilial phenotypic variability. Two loci are known for SPD (MIM 186000, MIM 608180) associated with mutations in HOXD13 and FBLN1, respectively. Here, we report further genetic heterogeneity for SDP. Employing a whole genomic screen, we demonstrate, in a large Pakistani kindred, that the classical phenotype of SPD maps on a new locus at chromosome 14q11.2-q12. The highest LOD score (Z(max) = 4.06) was obtained with microsatellite marker D14S264, and the multipoint LOD score reached a maximum of 5.01. Haplotype analysis revealed that the disease interval is flanked by microsatellite markers D14S283 and D14S1060, encompassing a physical distance of 10.72 Mb. We propose to allocate to this locus the symbol SPD3 (synpolydactyly 3), and to name the loci associated with HOXD13 or FBLN1 mutations SPD1 and SPD2, respectively.
- Published
- 2006
35. Breakthroughs in Optimization of Mechanical Properties of Nanostructured Metals and Alloys
- Author
-
Korukonda L. Murty, Khaled Youssef, Ronald O. Scattergood, and Carl C. Koch
- Subjects
Materials science ,Tension (physics) ,Metallurgy ,engineering.material ,Condensed Matter Physics ,Nanocrystalline material ,Grain size ,Nanocrystal ,engineering ,General Materials Science ,Graphite ,Cast iron ,Elongation ,Ductility - Abstract
While nanocrystalline metals can have strength and hardness values factors of 10 or more greater than their conventional grain size counterparts, ductility in tension has been disappointing, typically less than 2% elongation. This paper reviews the limitations to ductility in nanocrystalline materials and presents the results of recent breakthroughs wherein both high strength and good ductility are observed.
- Published
- 2005
36. The Work-Family Interface: Differentiating Balance and Fit
- Author
-
E. Jeffrey Hill, Maribeth C. Clarke, and Laura C. Koch
- Subjects
Cultural Studies ,Balance (accounting) ,Sociology and Political Science ,Marital satisfaction ,Work–family conflict ,Work (physics) ,Family activities ,Job satisfaction ,Family income ,Psychology ,Social psychology ,Work hours - Abstract
Work-family fit has recently emerged in work and family literature, comparable to work-family balance in that it represents interactions between work and family and yet distinct because it precedes balance and other outcomes. This study explores the relationship between, predictive factors of, and interactive moderating effects of work-family fit and work-family balance. Data are from a survey of business graduate school alumni (n = 387). Findings indicate that fit and balance are two separate constructs. Fit is uniquely predicted by work hours, age, family income, and household labor satisfaction. Balance is uniquely predicted by frequency of family activities. Job satisfaction and marital satisfaction predicted both fit and balance. Analyses suggest that fit is based more on the structural aspects of work-family interactions, whereas balance appears to be based more on the psychological factors. Job satisfaction, marital satisfaction, and frequency of family activities moderated the relationship between fit and balance.
- Published
- 2004
37. Muscle pathology in 57 patients with myotonic dystrophy type 2
- Author
-
Klaus V. Toyka, Christiane Schneider-Gold, Kenneth Ricker, Hans-Hilmar Goebel, Manuela C. Koch, Hanns Lochmüller, Benedikt Schoser, Dieter Pongratz, Wolfram Kress, and Peter Reilich
- Subjects
medicine.medical_specialty ,Pathology ,Muscle biopsy ,medicine.diagnostic_test ,Physiology ,business.industry ,Anatomical pathology ,medicine.disease ,Myotonia ,Myotonic dystrophy ,Proximal myotonic myopathy ,Cellular and Molecular Neuroscience ,Atrophy ,Physiology (medical) ,Biopsy ,medicine ,Histopathology ,Neurology (clinical) ,business - Abstract
We evaluated muscle biopsies from 57 patients with genetically confirmed myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM). Light microscopy showed myopathic together with “denervation-like” changes in almost all biopsies obtained from four different muscles: increased fiber size variation, internal nuclei, small angulated fibers, pyknotic nuclear clumps, and predominant type 2 fiber atrophy. Quantitative morphometry in 18 biopsies that were immunostained for myosin heavy chain confirmed a predominance of nonselective type 2 fiber atrophy. These histological changes were similar in all patients regardless of the site of biopsy, the predominant clinical symptoms and signs, and the clinical course. It is likely that, in a number of undiagnosed patients, DM2 is the underlying disorder. With a better understanding of the histopathological pattern in DM2, biopsies from patients with undiagnosed neuromuscular disorders can now be reevaluated. Muscle Nerve 29: 275–281, 2004
- Published
- 2004
38. Scleral collagen crosslinking (SXL) by riboflavin and blue light inhibits eye growth of young rabbits
- Author
-
C Gohler, Hp Iseli, Anett Karl, Mike Francke, Daniel Huster, C Koch, A Penk, Andreas Reichenbach, Nicole Körber, and Peter Wiedemann
- Subjects
medicine.medical_specialty ,genetic structures ,Chemistry ,Riboflavin ,General Medicine ,Anatomy ,eye diseases ,Sclera ,Ophthalmology ,Light intensity ,medicine.anatomical_structure ,Light energy ,Pathologic myopia ,medicine ,Eye growth ,Immunohistochemistry ,sense organs ,Blue light - Abstract
Purpose The application of riboflavin and blue light (for Collagen Crosslinking of scleral tissue; SXL) was proved as a possible therapeutic method to increase scleral stiffness and therefore, to inhibit eye growth in young rabbits. Methods For eye growth examination the sclera of young rabbit eyes were treated with riboflavin and 10 mW/cm² blue light. MR-Imaging and ultrasonic A scans were used to measure effects of SXL treatment on eye growth. Safety and efficacy parameters were determined using immunohistochemical and histological methods. Results Immunohistochemical and histological examinations showed no neurodegenerative side effects or signs of glial reactivity in retinal tissue beyond a light intensity of 400 mW/cm². Young animals treated with a minimal effective light energy dose of 10 mW/cm² displayed a significant reduction of their eye growth. The eye growth inhibition after SXL treatment maintained for at least 24 weeks. Conclusion The results confirm the idea that scleral collagen crosslinking by riboflavin/blue light is an applicable method to inhibit eye growth and therefore, it might be a treatment for pathologic myopia.
- Published
- 2014
39. Translation of the therapeutic approach of scleral collagen crosslinking (SXL) from animal to human
- Author
-
Andreas Reichenbach, Hp Iseli, C Gohler, Mike Francke, Carsten Schuldt, Nicole Körber, Peter Wiedemann, C Koch, Anett Karl, and U Rattunde
- Subjects
medicine.medical_specialty ,Materials science ,Energy dose ,Dose dependence ,Stiffness ,General Medicine ,Surgery ,Sclera ,Light dose ,Ophthalmology ,medicine.anatomical_structure ,Pathologic myopia ,medicine ,In patient ,medicine.symptom ,Blue light ,Biomedical engineering - Abstract
Purpose In our research project “collagen crosslinking of scleral tissue (SXL)”, the application of riboflavin and blue light has been proved as a possible therapeutic method to increase scleral stiffness. Nevertheless, it is necessary to develop a new application system applicable in human. Methods Rheology was used to investigate changes of sclera stiffness after SXL treatment. An adapted and modified blue light irradiations system has been developed to apply various blue light intensities. Results As a proof of principle, we demonstrate a dose dependent increase of scleral stiffness after application of various blue light energy dose rates. Increased biomechanical stiffness could be induced with light dose rates up to 200 mW/cm². However, the light application system used for animal surgery has serious limitations. The animal experiments revealed relevant technical parameters and helps to design a suitable substance and application system for usage in human. Conclusion The results confirm the idea that SXL by riboflavin and blue light irradiation is an applicable method to increase biomechanical stiffness of scleral tissue and therefore, it might be a treatment for pathologic myopia. For the therapeutic application in patients a special substance application and irradiation system has to be refined and developed further.
- Published
- 2014
40. A screen for mutations in human homologues of mice exencephaly genesTfap2? andMsx2 in patients with neural tube defects
- Author
-
Manuela C. Koch, Bärbel Richter, Valeria Capra, Elisabeth Strehl, Karolin Stegmann, Richard H. Finnell, Julia Boecker, August Ermert, and Ernestine T.K.N. Ngo
- Subjects
Embryology ,DNA, Complementary ,Genotype ,Health, Toxicology and Mutagenesis ,Molecular Sequence Data ,Receptors, Cell Surface ,Exencephaly ,Biology ,Toxicology ,medicine.disease_cause ,Loss of heterozygosity ,Mice ,Folic Acid ,Polymorphism (computer science) ,medicine ,Animals ,Humans ,Point Mutation ,Neural Tube Defects ,Allele ,Codon ,Spinal Dysraphism ,Gene ,Alleles ,Polymorphism, Single-Stranded Conformational ,Encephalocele ,Homeodomain Proteins ,Genetics ,Anencephaly ,Mutation ,Polymorphism, Genetic ,Base Sequence ,Point mutation ,Folate Receptors, GPI-Anchored ,Neural tube ,Exons ,medicine.disease ,Pedigree ,DNA-Binding Proteins ,medicine.anatomical_structure ,Transcription Factor AP-2 ,Carrier Proteins ,Gene Deletion ,Transcription Factors ,Developmental Biology - Abstract
Background Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2α and Msx2, which are expressed in the developing neural tube. Methods A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2α and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRα, and PAX1 already shown to be related to NTD. Results Two TFAP2α point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2α and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2α polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57–5.39). Conclusions Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases. Teratology 63:167–175, 2001. © 2001 Wiley-Liss, Inc.
- Published
- 2001
41. Temperature‐induced morphological evolution in polymer blends produced by cryogenic mechanical alloying
- Author
-
Carl C. Koch, Steven D. Smith, Harald Ade, A. P. Smith, and Richard J. Spontak
- Subjects
chemistry.chemical_classification ,Materials science ,Nanostructure ,Polymers and Plastics ,Annealing (metallurgy) ,General Chemical Engineering ,Organic Chemistry ,Polymer ,chemistry.chemical_compound ,chemistry ,Transmission electron microscopy ,Microscopy ,Materials Chemistry ,Polymer blend ,Methyl methacrylate ,Composite material ,Glass transition - Abstract
Novel nanoscale morphologies are achieved in blends of poly(methyl methacrylate) (PMMA) and either polyisoprene (PI) or poly(ethylene-alt-propylene) (PEP) produced by high-energy mechanical alloying at cryogenic temperatures. Since the blends are prepared as solid powders, they must be post-processed in the melt to be of practical relevance. In this study, we employ scanning transmission X-ray microscopy (STXM), transmission electron microscopy (TEM) and light microscopy (LM) to investigate the stability of nanostructural features and the dynamics of phase coarsening at elevated temperatures (above the glass transition temperature of milled PMMA). Substantial coarsening is observed in PEP/PMMA blends at relatively short times, indicating that the two polymers are highly immiscible and mobile at the conditions examined. The nanostructure evident in PI/PMMA blends is, however, more robust and undergoes less evolution due to milling-induced PI crosslinking. Instead of forming discrete dispersions in a PMMA matrix, the PI molecules organize into a fine network morphology upon annealing in the melt.
- Published
- 2000
42. High-Energy Cryogenic Blending and Compatibilizing of Immiscible Polymers
- Author
-
A. P. Smith, Steven D. Smith, Carl C. Koch, Richard J. Spontak, and Harald Ade
- Subjects
chemistry.chemical_classification ,High energy ,Materials science ,chemistry ,Chemical engineering ,Mechanics of Materials ,Mechanical Engineering ,Organic chemistry ,General Materials Science ,Polymer - Published
- 1999
43. Energetic stress, immunosuppression and the costs of an antibody response
- Author
-
Erik I. Svensson, Lars Råberg, Dennis Hasselquist, and C. Koch
- Subjects
Immune system ,Antibody response ,Antigen ,medicine.medical_treatment ,Immunology ,Basal metabolic rate ,medicine ,Immunosuppression ,Immunocompetence ,Thermoregulation ,Biology ,Attraction ,Ecology, Evolution, Behavior and Systematics - Abstract
1. Recently, there has been much interest in physiological trade-offs between parasite resistance and fitness-related traits such as secondary sexual characters or reproductive effort. More specifically it has been suggested that (i) energetically costly activities may suppress the immune system and (ii) that this immunosuppression is caused by costly immune defences competing with other bodily demands for scarce resources, e.g. energy. 2. The possibility was investigated of an energetically based trade-off between humoral (antibody-based) immunocompetence and other costly activities, by immunizing Blue Tits, Parus caeruleus, with novel antigens (proteins) thereby inducing antibody responses, and performing two experiments. In experiment i, one group of birds was subjected to cold stress, thereby increasing their daily energy expenditure and the effect on immune responsiveness was investigated. In experiment 2, the basal metabolic rate (BMR) of immunized birds was measured to investigate the energetic costs of mounting the antibody responses. 3. In experiment I, birds subject to increased energy turnover had significantly lower antibody responses, consistent with the hypothesis that environmental stress could suppress immunocompetence. However, in experiment 2 the energetic costs of these antibody responses were found to be low and at most 8-13% of BMR, indicating that adaptive resource allocation of energy was an unlikely explanation for the lowered immune responsiveness in the cold stress treatment (experiment 1). 4. It is concluded that our data provide some support to the idea that there may be a trade-off between immunocompetence and energetically costly activities such as thermoregulation, reproduction or mate attraction, although this trade-off may not necessarily be based on energy or nutrient limitation (i.e. resource allocation models). Two non-energetic explanations are briefly discussed, one adaptive and one non-adaptive, that could explain the immunosuppression in our study as well as in other behavioural and ecological contexts. (Less)
- Published
- 1998
44. Phenotypic-genotypic correlation will assist genetic counseling in 4q35-facioscapulohumeral muscular dystrophy
- Author
-
Margaret Williams, Julia Maynard, P.W. Lunt, Meena Upadhyaya, Manuela C. Koch, Peter S. Harper, Micheal Osborn, and Philip Jardine
- Subjects
musculoskeletal diseases ,Genetics ,Proband ,congenital, hereditary, and neonatal diseases and abnormalities ,Mutation ,Physiology ,Genetic counseling ,Biology ,medicine.disease_cause ,medicine.disease ,Cellular and Molecular Neuroscience ,Genetic linkage ,Physiology (medical) ,Genotype ,medicine ,Facioscapulohumeral muscular dystrophy ,Neurology (clinical) ,Muscular dystrophy ,Age of onset - Abstract
The wide range of severity in facioscapulohumeral muscular dystrophy (FSHD) complicates genetic advice, although onset age is youngest and severity is greatest in isolated cases. From 14 of 16 large FSHD families which are 4q35 linked, and from 25 of 34 isolated cases exhibiting a de novo D4F104S1 DNA fragment, we find a correlation between proband age at onset and FSHD-associated D4F104S1 fragment size (r = 0.56; P 85% of FSHD maps to 4q35, will facilitate genetic counseling. We propose that quantitative variation in a uniform mutation mechanism influences age at onset, but by deletion rather than expansion of DNA.
- Published
- 1995
45. Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections
- Author
-
C Koch, Jørn Nerup, S Lanng, and B Thorsteinsson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Vital capacity ,Pancreatic disease ,Adolescent ,Cystic Fibrosis ,medicine.medical_treatment ,Cystic fibrosis-related diabetes ,Gastroenterology ,Cystic fibrosis ,Body Mass Index ,Pulmonary function testing ,FEV1/FVC ratio ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Insulin ,Child ,Lung ,Respiratory Tract Infections ,Retrospective Studies ,business.industry ,General Medicine ,medicine.disease ,Respiratory Function Tests ,respiratory tract diseases ,Diabetes Mellitus, Type 1 ,Endocrinology ,Case-Control Studies ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business - Abstract
The effect of insulin therapy on lung function and lung infections was studied in a retrospective case-control design in 18 diabetic cystic fibrosis (CF) patients; 18 non-diabetic CF patients, matched for sex, age and presence of chronic Pseudomonas aeruginosa lung infection. served as controls. Parameters of CF clinical status were collected for six years before and two years after the onset of insulin therapy in the diabetic patients. Before onset of insulin therapy, body mass index (BMI) and forced vital capacity (FVC) in (pre)diabetic patients deviated increasingly from those in control patients. Decreases in BMI and lung function during the past three months before onset of insulin therapy were reverted within three months of insulin therapy. From three months to two years after onset of insulin therapy, differences in BMI and lung function diminished between diabetic and control patients. After two years of insulin therapy, BMI was similar in diabetic and non-diabetic patients and the percentage differences in forced expiratory volume in 1s (FEV1) and FVC between the two groups were similar to those found six years before the onset of insulin therapy. The finding that insulin therapy improves lung function in diabetic CF patients suggests strongly that the insidious decline in lung function seen during the years before the diagnosis of diabetes mellitus results from the pre-diabetic condition. After onset of insulin therapy, the percentages of sputum examinations positive for Haemophilus infuenzae and Streptococcus pneumoniae decreased in the diabetic patients, whereas parameters of lung infections with P. aeruginosa and Staphylococcus aureus remained unchanged. In conclusion, since insulin therapy improves lung function and reduces the number of infections with H. influenzae and S. pneumoniae in diabetic CF patients, we suggest that insulin therapy should be started when diabetes mellitus is diagnosed.
- Published
- 1994
46. ChemInform Abstract: Enantioselective Preparation of β-Alkyl-γ-butyrolactones from Functionalized Ketene Dithioacetals
- Author
-
A. R. Chamberlin and S. S. C. Koch
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Enantioselective synthesis ,Ketene ,General Medicine ,Medicinal chemistry ,Alkyl - Published
- 2010
47. Mixed axonal-demyelinating polyneuropathy as predominant manifestation of myotonic dystrophy
- Author
-
Reiner Benecke, Guido Stoll, Hans-Jürgen von Giesen, and Manuela C. Koch
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Physiology ,Diagnostico diferencial ,Neuropathology ,Myotonic dystrophy ,Cellular and Molecular Neuroscience ,Physiology (medical) ,Humans ,Myotonic Dystrophy ,Medicine ,Demyelinating polyneuropathy ,Axon ,business.industry ,Electrodiagnosis ,Middle Aged ,medicine.disease ,Myotonia ,Axons ,Mutational analysis ,medicine.anatomical_structure ,Mutation ,Neurology (clinical) ,business ,Neuroscience ,Polyneuropathy ,Demyelinating Diseases - Published
- 1994
48. Proximal myotonic myopathy syndrome in the absence of trinucleotide repeat expansions
- Author
-
Reiner Benecke, Guido Stoll, Hans-Jürgen von Giesen, Gabriele Arendt, and Manuela C. Koch
- Subjects
Male ,medicine.medical_specialty ,Physiology ,DNA Mutational Analysis ,Myotonic dystrophy ,Proximal myotonic myopathy ,Diagnosis, Differential ,Cellular and Molecular Neuroscience ,Physiology (medical) ,Internal medicine ,Humans ,Myotonic Dystrophy ,Medicine ,Myopathy ,Repetitive Sequences, Nucleic Acid ,Genetics ,business.industry ,Muscle weakness ,Middle Aged ,medicine.disease ,Myotonia ,Mutational analysis ,Endocrinology ,Mutation (genetic algorithm) ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Trinucleotide repeat expansion - Published
- 1995
49. Anti-HCV ELISA and RIBA reactivity in Portuguese blood donors and dialysis patients
- Author
-
Henrique Barros, T. Ramalhão, A. Rosa Araújo, Ademir Aparecido Pinhelli Mendes, C. Koch, H. Alves, and Mayra F. Costa
- Subjects
Anti hiv ,business.industry ,Immunology ,language ,Medicine ,Reactivity (chemistry) ,Hematology ,Portuguese ,Dialysis patients ,business ,language.human_language - Published
- 1993
50. Persönliches: Nachruf auf Frank Früngel
- Author
-
R. Germer, M. Hugenschmidt, St. Louis, W. Bötticher, H. Mach, C. Koch, and D. Ebeling
- Published
- 1995
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