12,506 research outputs found
In-line near infrared spectroscopy during freeze-drying as a tool to measure efficiency of hydrogen bond formation between protein and sugar, predictive of protein storage stability
Sugars are often used as stabilizers of protein formulations during freeze-drying. However, not all sugars are equally suitable for this purpose. Using in-line near-infrared spectroscopy during freeze-drying, it is shown here that hydrogen bond formation during freeze-drying, under secondary drying conditions in particular, can be related to the preservation of the functionality and structure of proteins during storage. The disaccharide trehalose was best capable of forming hydrogen bonds with the model protein, lactate dehydrogenase, thereby stabilizing it, followed by the molecularly flexible oligosaccharide inulin 4kDa. The molecularly rigid oligo- and polysaccharides dextran 5kDa and 70kDa, respectively, formed the least amount of hydrogen bonds and provided least stabilization of the protein. It is concluded that smaller and molecularly more flexible sugars are less affected by steric hindrance, allowing them to form more hydrogen bonds with the protein, thereby stabilizing it better
RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis
Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC
Generalized gaugings and the field-antifield formalism
We discuss the algebra of general gauge theories that are described by the
embedding tensor formalism. We compare the gauge transformations dependent and
independent of an invariant action, and argue that the generic transformations
lead to an infinitely reducible algebra. We connect the embedding tensor
formalism to the field-antifield (or Batalin-Vilkovisky) formalism, which is
the most general formulation known for general gauge theories and their
quantization. The structure equations of the embedding tensor formalism are
included in the master equation of the field-antifield formalism.Comment: 42 pages; v2: some clarifications and 1 reference added; version to
be published in JHE
Semiconductor charge qubit relaxation due to two-phonon processes
We theoretically study the relaxation of electron orbital states of a double
quantum dot system due to two-phonon processes. In particular, we calculate how
the relaxation rates depend on the separation distance between the quantum
dots, the strength of quantum dot confinement, and the lattice temperature.
Enhancement of the rates by specific inter-dot distances and lattice
temperatures, and the relative strength of different scattering channels are
discussed. Our results show that although at low temperatures ( K)
two-phonon processes are almost four orders of magnitude weaker compared to
one-phonon processes in relaxing electron orbital states, at room temperature
they are as important as one-phonon processes.Comment: Submitted to PR
Microarray technology and its effect on breast cancer (re)classification and prediction of outcome
SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Long-Term Results of Conservative Surgery and Radiotherapy for Ductal Carcinoma In Situ Using Lung Density Correction: The University of Michigan Experience
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72520/1/j.1524-4741.2007.00447.x.pd
Helicobacter Genotyping and Detection in Peroperative Lavage Fluid in Patients with Perforated Peptic Ulcer
Introduction and Objectives Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are present in patients with PPU and which genotype is dominant in this population. The secondary aim was to study the possibility of determining the H. pylori status in a way other than by biopsy.
Materials and Methods Serum samples, gastric tissue biopsies, lavage fluid, and fluid from the nasogastric tube were collec
Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use
Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 ± 4% of maximal O2 uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg−1 h−1) or without (CON placebo trial; water only). Continuous infusions with [U-13C] palmitate and [6,6-2H2] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (Ra) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 ± 19 and 57 ± 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA Ra and subsequent plasma FFA concentrations were lower, resulting in a 34 ± 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 ± 21 and 78 ± 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men
The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis
BACKGROUND: Internuclear ophthalmoparesis (INO) occurs in 15-52% of individuals with multiple sclerosis (MS) and is reliably detected by infrared oculography. Methods for diagnosing INO with infrared oculography and the association between INO and MS characteristics need confirmation. We aimed to describe INO prevalence and the clinical characteristics of individuals with MS and INO in a population-based cohort of individuals with MS born in the year 1966 (Project Y). METHODS: Previously described thresholds for the versional dysconjugacy index (VDI), assessed with standardized infrared oculography, were used to detect INO in participants of project Y. Clinical characteristics, visual functioning and complaints were compared between individuals with MS with INO and individuals with MS without INO. RESULTS: Two-hundred-twenty individuals with MS and 110 healthy controls were included. VDI values exceeding the threshold for INO presented in 53 (24%) individuals with MS and 19 controls (13%). INO was associated with male sex, greater disability, worse cognition and worse arm function in individuals with MS. There was no association with disease duration, visual functioning or complaints. CONCLUSIONS: INO is prevalent among individuals with MS aged fifty-three and related to clinical characteristics of MS. INO was more frequently detected in healthy controls than previous studies, implying that oculography based diagnosis of INO requires further refinement
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