Photonic information processing beyond Turing: an optoelectronic implementation of reservoir computing.

Many information processing challenges are difficult to solve with traditional Turing or von Neumann approaches. Implementing unconventional computational methods is therefore essential and optics provides promising opportunities. Here we experimentally demonstrate optical information processing using a nonlinear optoelectronic oscillator subject to delayed feedback.

Future emissions and atmospheric fate of HFC-1234yf from mobile air conditioners in Europe.

HFC-1234yf (2,3,3,3-tetrafluoropropene) is under discussion for replacing HFC-134a (1,1,1,2-tetrafluoroethane) as a cooling agent in mobile air conditioners (MACs) in the European vehicle fleet. Some HFC-1234yf will be released into the atmosphere, where it is almost completely transformed to the persistent trifluoroacetic acid (TFA). Future emissions of HFC-1234yf after a complete conversion of the European vehicle fleet were assessed.

A mixed fixed ratio/progressive ratio procedure reveals an apathy phenotype in the BAC HD and the z_Q175 KI mouse models of Huntington's disease.

Apathy, characterized by generally reduced interest in and likelihood to perform goal-directed actions, is a recognized symptom of Huntington's disease (HD), a devastating neurological disorder caused by a CAG repeat expansion of the Htt gene located on chromosome 4. The present experiments used a modified progressive ratio task that incorporated a fixed-ratio schedule of reinforcement component to assess consummatory behavior, and a progressive-ratio schedule component that required increasing numbers of lever-presses for successive reinforcers (0.01 ml of evaporated milk).

European emissions of halogenated greenhouse gases inferred from atmospheric measurements.

European emissions of nine representative halocarbons (CFC-11, CFC-12, Halon 1211, HCFC-141b, HCFC-142b, HCFC-22, HFC-125, HFC-134a, HFC-152a) are derived for the year 2009 by combining long-term observations in Switzerland, Italy, and Ireland with campaign measurements from Hungary. For the first time, halocarbon emissions over Eastern Europe are assessed by top-down methods, and these results are compared to Western European emissions. The employed inversion method builds on least-squares optimization linking atmospheric observations with calculations from the Lagrangian particle dispersion model FLEXPART.

Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile.

Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing α4β2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at α4β2-nAChRs.

Comparative psychology and the grand challenge of drug discovery in psychiatry and neurodegeneration.

Drug discovery for brain disorders is undergoing a period of upheaval. Faced with an empty drug pipeline and numerous failures of potential new drugs in clinical trials, many large pharmaceutical companies have been shrinking or even closing down their research divisions that focus on central nervous system (CNS) disorders. In this paper, we argue that many of the difficulties facing CNS drug discovery stem from a lack of robustness in pre-clinical (i.

Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity.

There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients.

Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms.

The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms.

Cell polarity in fission yeast: a matter of confining, positioning, and switching growth zones.

The two key processes in growth polarisation are the generation of a confined region and the correct positioning of that region. Fission yeast has greatly contributed to the study of cell polarisation, particularly in the aspect of growth site positioning, which involves the interphase microtubule cytoskeleton. Here we review the mechanisms of growth polarity in vegetatively growing fission yeast cells.

B1(+) phase mapping at 7 T and its application for in vivo electrical conductivity mapping.

In this study, a new approach to measure local electrical conductivity in tissue is presented, which is based on the propagating B1(+) phase and the homogeneous Helmholtz equation. This new MRI technique might open future opportunities for tumor and lesion characterization based on conductivity differences, while it may also find application in radio frequency safety assessment. Prerequisites for conductivity mapping using only the B1(+) phase (instead of the complex B1(+) field) are addressed.

Traveling-wave RF shimming and parallel MRI.

At sufficiently high Larmor frequencies, traveling electromagnetic waves along a magnet bore can be used for remote magnetic resonance excitation and detection, effectively using the bore as a waveguide. So far, this approach has relied only on the lowest waveguide modes and thus has not supported multiple-channel operation for radiofrequency shimming and parallel imaging. In this work, this limitation is addressed by establishing a larger number of propagating modes and tapping their spatial field diversity with multiple waveguide ports.

Automatic quantification of microtubule dynamics enables RNAi-screening of new mitotic spindle regulators.

The genetic integrity of every organism depends on the faithful partitioning of its genome between two daughter cells in mitosis. In all eukaryotes, chromosome segregation requires the assembly of the mitotic spindle, a bipolar array of dynamic microtubules. Perturbations in microtubule dynamics affect spindle assembly and maintenance and ultimately result in aberrant cell divisions.

Circadian Abnormalities in Motor Activity in a BAC Transgenic Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a progressive neurodegenerative disease marked by psychiatric and motor problems. Recently, these findings have been extended to deficits in sleep and circadian function that can be observed in HD patients and in HD mouse models, with abnormal sleep patterns correlating with symptom severity in patients. Here, we studied the behavior of the BAC HD mouse model using an 24/7 automated system; the results indicate significant lengthening of the circadian period in the mutant mice.

Controlling the interaction of electron and nuclear spins in a tunnel-coupled quantum dot.

We present a technique for manipulating the nuclear spins and the emission polarization from a single optically active quantum dot. When the quantum dot is tunnel coupled to a Fermi sea, we have discovered a natural cycle in which an electron spin is repeatedly created with resonant optical excitation. The spontaneous emission polarization and the nuclear spin polarization exhibit a bistability.

Electron tomography reveals a flared morphology on growing microtubule ends.

Microtubules (MTs) exhibit dynamic instability, alternating between phases of growth and shortening, mostly at their uncapped plus ends. Based on results from cryo-electron microscopy it was proposed that growing MTs display mainly curved sheets and blunt ends; during depolymerisation curled 'ramshorns' predominate. Observations of MTs in mitotic cells have suggested that the situation in vivo differs from that in vitro, but so far, a clear comparison between in vivo and in vitro results has not been possible because MT end structures could not be correlated directly with the dynamic state of that particular MT.

HD mouse models reveal clear deficits in learning to perform a simple instrumental response.

Mouse models of Huntington's disease (HD) were trained to acquire one of two simple instrumental responses (a lever press or a nosepoke) to obtain food reinforcement. Animals from several HD strains revealed apparently progressive deficits in this task, being significantly less able than littermate controls to perform the required responses, at ages where motor function is only mildly affected. These data could provide a simple way to measure learning deficits in these mouse models, likely related to the characteristic pattern of neural damage observed in HD mouse models.

The fission yeast XMAP215 homolog Dis1p is involved in microtubule bundle organization.

Microtubules are essential for a variety of fundamental cellular processes such as organelle positioning and control of cell shape. Schizosaccharomyces pombe is an ideal organism for studying the function and organization of microtubules into bundles in interphase cells. Using light microscopy and electron tomography we analyzed the bundle organization of interphase microtubules in S.

Simulative and experimental investigations on pressure-induced structural vibrations of a rear muffler.

The periodically blown out exhaust gas of a combustion engine may excite structural vibrations of the exhaust system. In addition to the noise of the orifice, these vibrations contribute to the overall noise radiation of the exhaust system. In this work, the excitation of structural vibrations of a rear muffler via the acoustic path is investigated both in experiments and simulations.

Divertor IR thermography on Alcator C-Mod.

Alcator C-Mod is a particularly challenging environment for thermography. It presents issues that will similarly face ITER, including low-emissivity metal targets, low-Z surface films, and closed divertor geometry. In order to make measurements of the incident divertor heat flux using IR thermography, the C-Mod divertor has been modified and instrumented.

The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties.

Triple reuptake inhibitors (TRIs) that block the dopamine transporter (DAT), norepinephrine transporter, and serotonin transporter are being developed as a new class of antidepressant that may have better efficacy and fewer side effects compared with traditional antidepressants. We describe a novel TRI, 2-[4-(4-chlorophenyl)-1-methylpiperidin-3-ylmethylsulfanyl]-1-(3-methylpiperidin-1-yl)-ethanone (JZAD-IV-22), that inhibits all three monoamine transporters with approximately equal potency in vitro. (+/-)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.

Within-session modulation of timed anticipatory responding: when to start responding.

The peak procedure is widely used in the study of interval timing with animals. Multiple timing measures can be derived from peak responding. These measures are typically presented as averages across many trials based on the implicit assumption that peak responding is stable throughout the session.

Optimal design of multiple-channel RF pulses under strict power and SAR constraints.

Parallel radio frequency transmission has recently been explored as a means of tailoring the spatial response of MR excitation. In particular, parallel transmission is increasingly used to accelerate radio frequency pulses that rely on time-varying gradient fields to achieve selectivity in multiple dimensions. The design of the underlying multiple-channel radio frequency waveforms is mostly based on regularized least-squares optimization in close analogy with image reconstruction in parallel imaging.

Serum-free cell culture: the serum-free media interactive online database.

Fetal bovine serum (FBS) is a ubiquitously used essential supplement in cell culture media. However, there are serious scientific and ethical concerns about the use of FBS regarding its harvest and production. During the last three decades, FBS could be substituted by other supplements or by the use of defined chemical components in serum-free cell culture.

Optimization of chemically defined cell culture media--replacing fetal bovine serum in mammalian in vitro methods.

Quality assurance is becoming increasingly important. Good laboratory practice (GLP) and good manufacturing practice (GMP) are now established standards. The biomedical field aims at an increasing reliance on the use of in vitro methods.