Psychiatric disorder pathogenesis is driven by interactions between multiple genetic and environmental risk factors. Many genes have been associated with increased risk for psychiatric disorder development. Polymorphisms in the dopamine transporter (DAT) gene have been linked to bipolar disorder (BD), schizophrenia, and attention deficit hyperactivity disorder (ADHD), and may functionally reduce DAT expression. Assessing animals with manipulated DAT expression in cross-species translatable tasks will bridge the gap between rodent and human work and aide development of better therapeutic options for patients. An example of disease-relevant manipulation is the DAT knockdown (KD) mouse line, created to model the hyperdopaminergic state thought to drive mania symptoms in patients with BD. In the behavioral pattern monitor (BPM), which quantitatively measures locomotor activity and exploratory behaviors in both rodents and humans, patients with mania and DAT KD mice both exhibit hyperactivity and increased exploration. Using a meta-analytic approach, I showed that BPM behavioral outcomes of DAT KD mice were reproducible. Given the need for reproducible models in psychiatric research to test novel therapeutics, I assessed potential anti-mania drugs in the DAT KD/BPM model. Nicotine acetylcholine receptor agonism, via chronic nicotine administration, partially normalized hyperactivity and hyperexploration in DAT KD mice.
Given the neurodevelopmental origins of many psychiatric disorders, it is important to assess early gene x environment interactions that might drive abnormal behaviors in patients. Increased psychiatric disorder diagnoses are observed in people born in late winter/early spring. While many factors have been studied to explain this observation, altered light and activity levels during gestation/early life have been largely ignored. In adult male rodents, reduced active (dark) period (short active (SA) photoperiod) exposure induces depression-relevant behaviors and a stress response. Here, I confirmed SA photoperiod-induced stress response in adult female mice. I then examined the behavioral effects of stress-inducing gestational/early life SA photoperiod exposure in heterozygous DAT KD (DAT-HT) and wildtype (WT) littermates. SA-born WT mice exhibited behavioral changes in multiple cross-species translatable tasks, while DAT-HT mice were largely resilient. Future work will assess SA-induced changes in placental gene expression that contribute to behaviors observed following gestational SA exposure in WT mice.
The ALS storage ring 500 MHz RF system uses two re-entrant accelerating cavities powered by a single 320kW PHILLIPS YK1305 klystron. During several years of initial operation, the RF cavities were not equipped with effective passive HOM damper systems. Longitudinal beam stability was achieved through cavity temperature control and the longitudinal feedback system (LFB), which was often operating at the edge of its capabilities. As a result, longitudinal beam stability was a significant operations issue at the ALS. During two consecutive shutdown periods (April 2002 and 2003) we installed E-type HOM dampers on the main and third harmonic cavities. These devices dramatically decreased the Q-values of the longitudinal anti-symmetric HOM modes. The next step is to damp the rest of the longitudinal HOM modes in the main cavities below the synchrotron radiation damping level. This will hopefully eliminate the need for the LFB and set the stage for a possible increase in beam current. The "waveguide" type of HOM damper was the only option that didn't significantly compromise the vacuum performance of the RF cavity. The design process and the results of the low level measurements of the new waveguide dampers are presented in this paper.
The recent energy crisis in California has led us to investigate the high power RF systems at the Advanced Light Source (ALS) in order to decrease the energy consumption and power costs. We found the Storage Ring Klystron Power Amplifier system operating as designed but with significant power waste. A simple proportional-integrator (PI) analog loop, which controls the klystron collector beam current, as a function of the output RF power, has been designed and installed. The design considerations, besides efficiency improvement, were to interface to the existing system without major expense. They were to also avoid the klystron cathode power supply filter's resonance in the loop's dynamics, and prevent a conflict with the existing Cavity RF Amplitude Loop dynamics. This efficiency loop will allow us to save up to 700 MW-hours of electrical energy per year and increase the lifetime of the klystron.
The main source of narrowband impedance in the Advanced Light Source (ALS) are higher order modes (HOMs) of the two main RF and three third harmonic cavities. These HOMs drive longitudinal and transverse coupled bunch instabilities, which are controlled using active beam feedback systems. The dominant longitudinal HOMs in both systems are TM011-like modes with the R/Q factor an order of magnitude higher than all other longitudinal modes. To reduce the growth rates within the range of the longitudinal feedback system (LFB), these modes were tuned away from beam resonances by means of cooling water temperature control (main rf system), and the combination of two tuners (third harmonic system). To improve the reliability of the longitudinal dampening system, we have built and installed E-type HOM dampers for the fundamental and harmonic cavities. We present the design, commissioning and performance of the HOM dampers in this paper.
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