193 research outputs found
Inclusion of temperature effects in a model of magnetoelasticity
In this paper, we report on temperature effects associated with elastic electromagnetic forming by pulsed electromagnetic fields in inhomogeneous, linear, and lossy media. In a previous paper, we discussed the electromagnetic forces associated with these pulsed electromagnetic fields. Here, we calculate the temperature rise from the equation of heat flow in an isolated object to be deformed. The temperature rise is included in the elastodynamic problem to be solved for the presence of electromagnetic forces, and as a consequence the thermoelastic field can be obtained. As an example, we calculate the thermoelastic field in a hollow cylindrical object
The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function
Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis
Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson’s Disease and Dementia with Lewy Bodies
Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, β-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and DLB as well as age-matched non-demented controls (n = 15/group) using fluorometric assays. Decreased activity of GCase (− 21%) and of cathepsin D (− 15%) was found in the SN and frontal cortex of patients with PD and DLB compared to controls, respectively. Population stratification was applied based on GBA genotype, showing substantially lower GCase activity (~ − 40%) in GBA variant carriers in all regions. GCase activity was further significantly decreased in the SN of PD and DLB patients without GBA variants in comparison to controls without GBA variants. Our results show decreased GCase activity in brains of PD and DLB patients with and without GBA variants, most pronounced in the SN. The results of our study confirm findings from previous studies, suggesting a role for GCase in GBA-associated as well as sporadic PD and DLB
Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays
Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care
Treatment-resistant psychotic symptoms and the 15q11.2 BP1–BP2 (Burnside-Butler) deletion syndrome: case report and review of the literature
The 15q11.2 BP1-BP2 (Burnside-Butler) deletion is a rare copy number variant impacting four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5), and carries increased risks for developmental delay, intellectual disability, and neuropsychiatric disorders (attention-deficit/hyperactivity disorder, autism, and psychosis). In this case report (supported by extensive developmental information and medication history), we present the complex clinical portrait of a 44-year-old woman with 15q11.2 BP1-BP2 deletion syndrome and chronic, treatment-resistant psychotic symptoms who has resided nearly her entire adult life in a long-term state psychiatric institution. Diagnostic and treatment implications are discussed
The necessity of drawing up the annual production plan and the importance of establishment crop structure for next agricultural year
Planning represents establishment and substantiate the objectives, accomplish tasks and necessary resources for appropriate period plan ( of perspective, annual, quarterly, monthly). Drawing up annual production plan into a ferm is required primarily for evolution or involution recorded by economical phenomenes, which directly determines the operation of the farm. After determining the annual production plan can establish structures and cultures for the next agricultural year using modeling and simulation methods. Following the application of modeling and simulation methods in a farm resulting optimal dimensions of business operations with profit maximization in terms of economic efficiency increased
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