A Bright, Slow Cryogenic Molecular Beam Source for Free Radicals

We demonstrate and characterize a cryogenic buffer gas-cooled molecular beam source capable of producing bright beams of free radicals and refractory species. Details of the beam properties (brightness, forward velocity distribution, transverse velocity spread, rotational and vibrational temperatures) are measured under varying conditions for the molecular species SrF. Under typical conditions we produce a beam of brightness 1.2 x 10^11 molecules/sr/pulse in the rovibrational ground state, with 140 m/s forward velocity and a rotational temperature of approximately 1 K. This source compares favorably to other methods for producing beams of free radicals and refractory species for many types of experiments. We provide details of construction that may be helpful for others attempting to use this method.Comment: 15 pages, 14 figure

Time-dependent Stochastic Modeling of Solar Active Region Energy

A time-dependent model for the energy of a flaring solar active region is presented based on a stochastic jump-transition model (Wheatland and Glukhov 1998; Wheatland 2008; Wheatland 2009). The magnetic free energy of the model active region varies in time due to a prescribed (deterministic) rate of energy input and prescribed (random) flare jumps downwards in energy. The model has been shown to reproduce observed flare statistics, for specific time-independent choices for the energy input and flare transition rates. However, many solar active regions exhibit time variation in flare productivity, as exemplified by NOAA active region AR 11029 (Wheatland 2010). In this case a time-dependent model is needed. Time variation is incorporated for two cases: 1. a step change in the rates of flare jumps; and 2. a step change in the rate of energy supply to the system. Analytic arguments are presented describing the qualitative behavior of the system in the two cases. In each case the system adjusts by shifting to a new stationary state over a relaxation time which is estimated analytically. The new model retains flare-like event statistics. In each case the frequency-energy distribution is a power law for flare energies less than a time-dependent rollover set by the largest energy the system is likely to attain at a given time. For Case 1, the model exhibits a double exponential waiting-time distribution, corresponding to flaring at a constant mean rate during two intervals (before and after the step change), if the average energy of the system is large. For Case 2 the waiting-time distribution is a simple exponential, again provided the average energy of the system is large. Monte Carlo simulations of Case~1 are presented which confirm the analytic estimates. The simulation results provide a qualitative model for observed flare statistics in active region AR 11029.Comment: 25 pages, 9 figure

Opportunities for mesoscopics in thermometry and refrigeration: Physics and applications

This review presents an overview of the thermal properties of mesoscopic structures. The discussion is based on the concept of electron energy distribution, and, in particular, on controlling and probing it. The temperature of an electron gas is determined by this distribution: refrigeration is equivalent to narrowing it, and thermometry is probing its convolution with a function characterizing the measuring device. Temperature exists, strictly speaking, only in quasiequilibrium in which the distribution follows the Fermi-Dirac form. Interesting nonequilibrium deviations can occur due to slow relaxation rates of the electrons, e.g., among themselves or with lattice phonons. Observation and applications of nonequilibrium phenomena are also discussed. The focus in this paper is at low temperatures, primarily below 4 K, where physical phenomena on mesoscopic scales and hybrid combinations of various types of materials, e.g., superconductors, normal metals, insulators, and doped semiconductors, open up a rich variety of device concepts. This review starts with an introduction to theoretical concepts and experimental results on thermal properties of mesoscopic structures. Then thermometry and refrigeration are examined with an emphasis on experiments. An immediate application of solid-state refrigeration and thermometry is in ultrasensitive radiation detection, which is discussed in depth. This review concludes with a summary of pertinent fabrication methods of presented devices.Comment: Close to the version published in RMP; 59 pages, 35 figure

Consensus Paper: Cerebellum and Social Cognition.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions

Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch