Comparison of IMU Measurements of Curling Stone Dynamics with a Numerical Model

Abstract Despite almost a century of research, the question of what causes a curling stone to curl (move perpendicular to its initial direction of motion) has no complete answer. Many hypotheses have been formulated, but none has been able to account quantitatively for the full magnitude of the observed curl. The objective of this research was to equip a curling stone with an inertial measurement unit (IMU) and measure its motion, in order to verify a previously published, numerical model of curling stone dynamics. Low cost, small size, accuracy, ease of programming and operation, wireless data communication, and a data-sampling rate near 1 kHz, were selection criteria and constraints for the instrument package. We used the MicroStrain 3DM-GX4-25 system. This is a MEMS-based IMU with a tri-axial gyroscope and a tri-axial linear accelerometer. It was mounted and interfaced with a Bluetooth transmitter, on a curling stone handle. The data were streamed to a host laptop and displayed graphically in real time. Post-processing of the data included filtering and time-integration in order to obtain linear and angular velocities, and displacements. We have compared our experimental results with trajectory data calculated using a previously published numerical model, based on a thermodynamic approach to ice friction. While the observed longitudinal and angular motions are captured reasonably well by the model (errors of about 5% or less), no curl is predicted by the model

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates

Ex vivo continuous Overhauser nuclear dynamic polarization in a SQUID-based ultralow field magnetic resonance imaging system

Overhauser Dynamic Nuclear Polarization (ODNP) is a method to achieve continuous hyperpolarization in MR measurements. Here, the polarization of free radicals is transferred to 1H using High Frequency (HF) pulses at the electron Larmor frequency. At UltraLow Fields (ULF) the frequency of the HF pulse lies in the range of several 100 MHz and is able to penetrate large sample volumes, making continuous in vivo ODNP measurements possible. Since conventional Faraday coils are not sensitive enough at ULF, a Superconducting QUantum Interference Device (SQUID) based detector is employed. First ex vivo images using ODNP enhanced MR have been acquired successfully