Chronobiology of Epilepsy

A fine balance between neuronal excitation and inhibition governs the physiological state of the brain. It has been hypothesized that when this balance is lost as a result of excessive excitation or reduced inhibition, pathological states such as epilepsy emerge. Decades of investigation have shown this to be true in vitro. However, in vivo evidence of the emerging imbalance during the "latent period" between the initiation of injury and the expression of the first spontaneous behavioral seizure has not been demonstrated. Here, we provide the first demonstration of this emerging imbalance between excitation and inhibition in vivo by employing long term, high temporal resolution, and continuous local field recordings from microelectrode arrays implanted in an animal model of limbic epilepsy. We were able to track both the inhibitory and excitatory postsynaptic field activity during the entire latent period, from the time of injury to the occurrence of the first spontaneous epileptic seizure. During this latent period we observe a sustained increase in the firing rate of the excitatory postsynaptic field activity, paired with a subsequent decrease in the firing rate of the inhibitory postsynaptic field activity within the CA1 region of the hippocampus. Firing rates of both excitatory and inhibitory CA1 field activities followed a circadian- like rhythm, which is locked near in-phase in controls and near anti-phase during the latent period. We think that these observed changes are implicated in the occurrence of spontaneous seizure onset following injury

Histogram-based models on non-thin section chest CT predict invasiveness of primary lung adenocarcinoma subsolid nodules.

109 pathologically proven subsolid nodules (SSN) were segmented by 2 readers on non-thin section chest CT with a lung nodule analysis software followed by extraction of CT attenuation histogram and geometric features. Functional data analysis of histograms provided data driven features (FPC1,2,3) used in further model building. Nodules were classified as pre-invasive (P1, atypical adenomatous hyperplasia and adenocarcinoma in situ), minimally invasive (P2) and invasive adenocarcinomas (P3). P1 and P2 were grouped together (T1) versus P3 (T2). Various combinations of features were compared in predictive models for binary nodule classification (T1/T2), using multiple logistic regression and non-linear classifiers. Area under ROC curve (AUC) was used as diagnostic performance criteria. Inter-reader variability was assessed using Cohen's Kappa and intra-class coefficient (ICC). Three models predicting invasiveness of SSN were selected based on AUC. First model included 87.5 percentile of CT lesion attenuation (Q.875), interquartile range (IQR), volume and maximum/minimum diameter ratio (AUC:0.89, 95%CI:[0.75 1]). Second model included FPC1, volume and diameter ratio (AUC:0.91, 95%CI:[0.77 1]). Third model included FPC1, FPC2 and volume (AUC:0.89, 95%CI:[0.73 1]). Inter-reader variability was excellent (Kappa:0.95, ICC:0.98). Parsimonious models using histogram and geometric features differentiated invasive from minimally invasive/pre-invasive SSN with good predictive performance in non-thin section CT

Effects of Hypohydration on Muscular Performance in Females: An Ongoing Study

Dehydration (~3%) has been shown to negatively affect anaerobic performance. A majority of this research has been conducted using male participants. Like males, females have been shown to underestimate sweat loss, which could lead to insufficient rehydration and thus hypohydration. Additionally, due to differences in thermoregulation, it is possible that females respond to hypohydration differently than males. To date, no research has examined the effects of previous night dehydration on muscular performance in females. PURPOSE: The purpose of this ongoing study was to determine the effects of previous night dehydration on muscular strength, muscular endurance, lower body power, and perceptual measures in resistance trained females. METHODS: Healthy, resistance trained females (n = 7) completed two bouts of resistance exercise, either dehydrated (~3% body weight) (DT) or heat exposed with fluid replacement (HT). Each exercise bout consisted of one rep maximum (1RM) for bench press followed by 5 sets to failure of 75% of 1RM, 1RM for leg press followed by 5 sets to failure of 75% of 1RM, and vertical jump assessment. Participants estimated ratings of perceived exertion (RPE) after each exercise. Session RPE (SRPE) was estimated 5 minutes following completion of the protocol and estimations for feelings of recovery (PRS), perceived readiness to exercise (PR), thirst, and sleep quality were estimated prior to workouts. RESULTS: Analysis revealed a bench press 1RM (p = 0.05) and leg press 1RM (p = 0.03) were significantly lower for DT (bench: 95.0 ± 34.0; leg press: 461.4 ± 141.7) compared to HT (bench: 97.9 ± 34.3; leg press: 500.0 ± 141.0). There was no difference in total reps completed for bench press (p = 0.32) or leg press (p = 0.37) for DT (bench press: 31.0 ± 6.7; leg press: 47.9 ± 21.6) compared to HT (bench press: 31.7 ± 5.0; leg press: 49.6 ± 22.8). There was no significant difference (p = 0.15) for vertical jump height (DT: 17.6 ± 2.2, HT: 18.1 ± 2.6). RPE was not significantly different following bench press (p = 0.5) (DT: 7.1 ± 1.1, HT: 7.1 ± 0.9) or leg press (p = 0.41) (DT: 6.7 ± 0.5, HT: 6.9 ± 1.7). SRPE was significantly higher (p = 0.05) for DT (6.6 ± 0.5) vs HT (5.9 ± 0.7). Significant differences for PRS (p = 0.03) (DT: 5.4 ± 2.2, HT: 7.05 ± 1.3) and PR (p = 0.01) (DT: 3.9 ± 0.9, HT: 2.6 ± 0.5) indicate participants expected impaired performance during DT. Feelings of thirst were significantly higher (p = 0.001) for DT (6.5 ± 2.5) vs HT (2.1 ± 2.3). Estimations of sleep quality were significantly lower (p = 0.05) for DT (4.3 ± 3.3) vs HT (7.2 ± 2.1). CONCLUSION: Even though only preliminary data from a presently ongoing study, the current results suggest that previous night dehydration has a negative influence on both performance and perceptual measures in resistance trained females

Ubiquitin Proteasome System Activity is Suppressed by Curcumin Following Exercise-Induced Muscle Damage in Human Skeletal Muscle

PURPOSE: Curcumin is a natural polyphenolic compound with antioxidant and anti-inflammatory properties. In vitro and in vivo animal studies have demonstrated that exposure to curcumin leads to dysregulation of the ubiquitin-proteasome system (UPS). However, to date, no study has investigated curcumin’s ability to influence UPS activity in a human model. Therefore, the purpose of this study was to investigate the effects of curcumin supplementation on markers of UPS activity in the presence of elevations in UPS activity due to exercise-induced muscle damage. METHODS: Twenty-three recreationally active male and female participants between the ages of 18-30 were randomized into a curcumin (CUR; n=11) or placebo (PLA; n=12) group. Both groups were instructed to consume 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45 minute eccentrically-biased muscle damaging treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) analyses were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise-induced muscle damage. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p≤0.05. RESULTS: Both groups had a significant time effect for DOMS (p \u3c .001). Pairwise comparisons indicated DOMS was significantly greater from baseline at all time points except 72 hours following muscle damage. No significant differences were found for USP19 between groups. Regardless of time, a significant main effect for condition was observed for ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) where CUR was significantly lower than PLA. Additionally, a significant main effect for gender was observed for MAFbx/Atrogin-1 (p=.013) where females were greater than males. A significant group x gender interaction was found for chymotrypsin-like protease (p = .049) where males had lower values with curcumin supplementation while females had slightly higher. CONCLUSION: Curcumin supplementation in humans does appear to dysregulate UPS activity in the presence of exercise-induced muscle damage. Specifically, curcumin’s ability to suppress protein ubiquination provides preliminary evidence of curcumin supplementation’s potential therapeutic role in decreasing protein degradation associated with skeletal muscle damage and perhaps other atrophic scenarios

The Physical Basis for Long-lived Electronic Coherence in Photosynthetic Light Harvesting Systems

The physical basis for observed long-lived electronic coherence in photosynthetic light-harvesting systems is identified using an analytically soluble model. Three physical features are found to be responsible for their long coherence lifetimes: i) the small energy gap between excitonic states, ii) the small ratio of the energy gap to the coupling between excitonic states, and iii) the fact that the molecular characteristics place the system in an effective low temperature regime, even at ambient conditions. Using this approach, we obtain decoherence times for a dimer model with FMO parameters of $\approx$ 160 fs at 77 K and $\approx$ 80 fs at 277 K. As such, significant oscillations are found to persist for 600 fs and 300 fs, respectively, in accord with the experiment and with previous computations. Similar good agreement is found for PC645 at room temperature, with oscillations persisting for 400 fs. The analytic expressions obtained provide direct insight into the parameter dependence of the decoherence time scales.Comment: 5 figures; J. Phys. Chem. Lett. (2011

Hamiltonian 2-forms in Kahler geometry, III Extremal metrics and stability

This paper concerns the explicit construction of extremal Kaehler metrics on total spaces of projective bundles, which have been studied in many places. We present a unified approach, motivated by the theory of hamiltonian 2-forms (as introduced and studied in previous papers in the series) but this paper is largely independent of that theory. We obtain a characterization, on a large family of projective bundles, of those `admissible' Kaehler classes (i.e., the ones compatible with the bundle structure in a way we make precise) which contain an extremal Kaehler metric. In many cases, such as on geometrically ruled surfaces, every Kaehler class is admissible. In particular, our results complete the classification of extremal Kaehler metrics on geometrically ruled surfaces, answering several long-standing questions. We also find that our characterization agrees with a notion of K-stability for admissible Kaehler classes. Our examples and nonexistence results therefore provide a fertile testing ground for the rapidly developing theory of stability for projective varieties, and we discuss some of the ramifications. In particular we obtain examples of projective varieties which are destabilized by a non-algebraic degeneration.Comment: 40 pages, sequel to math.DG/0401320 and math.DG/0202280, but largely self-contained; partially replaces and extends math.DG/050151

Intrasubband and Intersubband Electron Relaxation in Semiconductor Quantum Wire Structures

We calculate the intersubband and intrasubband many-body inelastic Coulomb scattering rates due to electron-electron interaction in two-subband semiconductor quantum wire structures. We analyze our relaxation rates in terms of contributions from inter- and intrasubband charge-density excitations separately. We show that the intersubband (intrasubband) charge-density excitations are primarily responsible for intersubband (intrasubband) inelastic scattering. We identify the contributions to the inelastic scattering rate coming from the emission of the single-particle and the collective excitations individually. We obtain the lifetime of hot electrons injected in each subband as a function of the total charge density in the wire.Comment: Submitted to PRB. 20 pages, Latex file, and 7 postscript files with Figure

Restrictive Breathing Mask Reduces Total Repetitions in Resistance-Trained Males: An Ongoing Study

Recently a popular exercise training device has been developed, which has been promoted by companies as a training aid, known as a restrictive breathing mask (RBM).The RBM is designed to simulate training at higher altitudes and has become commonplace for individuals to utilize during resistance-training sessions. PURPOSE: The purpose of this study was to examine the impact of a RBM on muscle performance and perceptual measures in resistance-trained males. METHODS: A cross-over study design was utilized in 9 resistance-trained males with performance trials separated by 7 days. A baseline strength testing session was completed for 12RM for squat, leg press, and leg extension. Participants completed the lower body workout with no mask or RBM. After the initial warm up, participants completed 4 sets of reps to failure of squats, leg press, and leg extension with 2 minutes rest between sets and 3 minutes between exercises. Heart rate was collected immediately post set. Participants completed a 10cm visual stress scale immediately post resistance training session and Session RPE (SRPE) was collected 10 minutes post. Paired T-tests were utilized to analyze total session reps, SRPE, average post set session heart rate, and session stress scale. RESULTS: There was a significant reduction in total session reps during the RBM trial compared to the no mask trial (p\u3c 0.001). SRPE was significantly higher during the RBM trial compared to the no mask trial (p= 0.003). There was a significant elevation in perceived stress during the RBM trial (p= 0.01). Finally, there was a statistically significant increase in post set heart rate during the RBM session (p=0.04) CONCLUSION: Based on the performance variables, it appears that a RBM reduces the total repetitions that an individual can complete during an acute bout of resistance training, while also increasing the perceived difficulty and stressfulness of the bout. Subsequently, a reduction in mechanical stimuli could result in a diminished hypertrophic response over time