A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles.

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g., schizophrenia (SCZ)], suggestive of brain functionality, here we characterize piggyBac transposable element-derived 1 (PGBD1). PGBD1 is nonmonotreme mammal-specific and under purifying selection, consistent with functionality. The gene body of human PGBD1 retains much of the original DNA transposon but has additionally captured SCAN and KRAB domains. Despite gene body retention, PGBD1 has lost transposition abilities, thus transposase functionality is absent. PGBD1 no longer recognizes piggyBac transposon-like inverted repeats, nonetheless PGBD1 has DNA binding activity. Genome scale analysis identifies enrichment of binding sites in and around genes involved in neuronal development, with association with both histone activating and repressing marks. We focus on one of the repressed genes, the long noncoding RNA NEAT1, also dysregulated in SCZ, the core structural RNA of paraspeckles. DNA binding assays confirm specific binding of PGBD1 both in the NEAT1 promoter and in the gene body. Depletion of PGBD1 in neuronal progenitor cells (NPCs) results in increased NEAT1/paraspeckles and differentiation. We conclude that PGBD1 has evolved core regulatory functionality for the maintenance of NPCs. As paraspeckles are a mammal-specific structure, the results presented here show a rare example of the evolution of a novel gene coupled to the evolution of a contemporaneous new structure.

Origination of free-form micro-optical elements using one- and two-photon grayscale laser lithography.

We discuss and describe the development of an origination process for planar free-form micro-optical elements from a given optical design. The targeted masters serve as origination structures for a roll-to-roll mass fabrication process. Specifically targeted are complex, optically smooth, surface relief structures with variable structure heights in the range of 1-20 µm, with typical lateral sizes of more than 5 µm. The area of the targeted masters is in the range of 1cm2. The main part of the paper is devoted to the description of a self-developed grayscale laser direct-write platform enabling one- and two-photon absorption lithography, also in combination on one and the same sample. In the following, we describe both methods and show that both lead to excellent structural quality of surface micro-relief structures. As a showcase of what the system can do in principle, we designed and fabricated free-form micro-optical elements to project light from an LED as a defined light pattern onto a wall. The proper optical functionality of the fabricated element was shown within a demonstrator setup.

Dysfunctional approach behavior triggered by alcohol-unrelated Pavlovian cues predicts long-term relapse in alcohol dependence.

We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers.

Salinity drives meiofaunal community structure dynamics across the Baltic ecosystem.

Coastal benthic biodiversity is under increased pressure from climate change, eutrophication, hypoxia, and changes in salinity due to increase in river runoff. The Baltic Sea is a large brackish system characterized by steep environmental gradients that experiences all of the mentioned stressors. As such it provides an ideal model system for studying the impact of on-going and future climate change on biodiversity and function of benthic ecosystems. Meiofauna (animals < 1 mm) are abundant in sediment and are still largely unexplored even though they are known to regulate organic matter degradation and nutrient cycling. In this study, benthic meiofaunal community structure was analysed along a salinity gradient in the Baltic Sea proper using high-throughput sequencing. Our results demonstrate that areas with higher salinity have a higher biodiversity, and salinity is probably the main driver influencing meiofauna diversity and community composition. Furthermore, in the more diverse and saline environments a larger amount of nematode genera classified as predators prevailed, and meiofauna-macrofauna associations were more prominent. These findings show that in the Baltic Sea, a decrease in salinity resulting from accelerated climate change will probably lead to decreased benthic biodiversity, and cause profound changes in benthic communities, with potential consequences for ecosystem stability, functions and services.

Ultrafast Coherent Control of Condensed Matter with Attosecond Precision.

Coherent control is a technique to manipulate wave functions of matter with light. Coherent control of isolated atoms and molecules in the gas phase is well-understood and developed since the 1990s, whereas its application to condensed matter is more difficult because its coherence lifetime is shorter. We have recently applied this technique to condensed matter samples, one of which is solid para-hydrogen ( p-H2). Intramolecular vibrational excitation of solid p-H2 gives an excited vibrational wave function called a "vibron", which is delocalized over many hydrogen molecules in a manner similar to a Frenkel exciton. It has a long coherence lifetime, so we have chosen solid p-H2 as our first target in the condensed phase. We shine a time-delayed pair of femtosecond laser pulses on p-H2 to generate vibrons. Their interference results in modulation of the amplitude of their superposition. Scanning the interpulse delay on the attosecond time scale gives a high interferometric contrast, which demonstrates the possibility of using solid p-H2 as a carrier of information encoded in the vibrons. In the second example, we have controlled the terahertz collective phonon motion, called a "coherent phonon", of a single crystal of bismuth. We employ an intensity-modulated laser pulse, whose temporal envelope is modulated with terahertz frequency by overlap of two positively chirped laser pulses with their adjustable time delay. This modulated laser pulse is shined on the bismuth crystal to excite its two orthogonal phonon modes. Their relative amplitudes are controlled by tuning the delay between the two chirped pulses on the attosecond time scale. Two-dimensional atomic motion in the crystal is thus controlled arbitrarily. The method is based on the simple, robust, and universal concept that in any physical system, two-dimensional particle motion is decomposed into two orthogonal one-dimensional motions, and thus, it is applicable to a variety of condensed matter systems. In the third example, the double-pulse interferometry used for solid p-H2 has been applied to many-body electronic wave functions of an ensemble of ultracold rubidium Rydberg atoms, hereafter called a "strongly correlated ultracold Rydberg gas". This has allowed the observation and control of many-body electron dynamics of more than 40 Rydberg atoms interacting with each other. This new combination of ultrafast coherent control and ultracold atoms offers a versatile platform to precisely observe and manipulate nonequilibrium dynamics of quantum many-body systems on the ultrashort time scale. These three examples are digested in this Account.

Partial Optomechanical Refrigeration via Multimode Cold-Damping Feedback.

We provide a fully analytical treatment for the partial refrigeration of the thermal motion of a quantum mechanical resonator under the action of feedback. As opposed to standard cavity optomechanics where the aim is to isolate and cool a single mechanical mode, the aim here is to extract the thermal energy from many vibrational modes within a large frequency bandwidth. We consider a standard cold-damping technique, where homodyne readout of the cavity output field is fed into a feedback loop that provides a cooling action directly applied on the mechanical resonator. Analytical and numerical results predict that low final occupancies are achievable independent of the number of modes addressed by the feedback, as long as the cooling rate is smaller than the intermode frequency separation. For resonators exhibiting a few nearly degenerate pairs of modes, cooling is less efficient and a weak dependence on the number of modes is obtained. These scalings hint toward the design of frequency-resolved mechanical resonators, where efficient refrigeration is possible via simultaneous cold-damping feedback.

Langevin Approach to Quantum Optics with Molecules.

We investigate the interaction between light and molecular systems modeled as quantum emitters coupled to a multitude of vibrational modes via a Holstein-type interaction. We follow a quantum Langevin equations approach that allows for analytical derivations of absorption and fluorescence profiles of molecules driven by classical fields or coupled to quantized optical modes. We retrieve analytical expressions for the modification of the radiative emission branching ratio in the Purcell regime and for the asymmetric cavity transmission associated with dissipative cross talk between upper and lower polaritons in the strong coupling regime. We also characterize the Förster resonance energy transfer process between donor-acceptor molecules mediated by the vacuum or by a cavity mode.

Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.

Effects of alcohol intoxication on self-reported drinking patterns, expectancies, motives and personality: a randomized controlled experimental study.

Alcohol intoxication may affect self-reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use-related temperament traits. We found that alcohol significantly increased self-reported expectancies (tension reduction) and motives (conformity; η2  = .16-.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr  ≥ .118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr  ≥ .462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self-reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self-report measures related to alcohol consumption.

Attosecond Control of Restoration of Electronic Structure Symmetry.

Laser pulses can break the electronic structure symmetry of atoms and molecules by preparing a superposition of states with different irreducible representations. Here, we discover the reverse process, symmetry restoration, by means of two circularly polarized laser pulses. The laser pulse for symmetry restoration is designed as a copy of the pulse for symmetry breaking. Symmetry restoration is achieved if the time delay is chosen such that the superposed states have the same phases at the temporal center. This condition must be satisfied with a precision of a few attoseconds. Numerical simulations are presented for the C_{6}H_{6} molecule and ^{87}Rb atom. The experimental feasibility of symmetry restoration is demonstrated by means of high-contrast time-dependent Ramsey interferometry of the ^{87}Rb atom.

Sisyphus cooling of electrically trapped polyatomic molecules.

Polar molecules have a rich internal structure and long-range dipole-dipole interactions, making them useful for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where various effects are predicted in many-body physics, quantum information science, ultracold chemistry and physics beyond the standard model. Whereas a wide range of methods to produce cold molecular ensembles have been developed, the cooling of polyatomic molecules (that is, with three or more atoms) to ultracold temperatures has seemed intractable. Here we report the experimental realization of optoelectrical cooling, a recently proposed cooling and accumulation method for polar molecules. Its key attribute is the removal of a large fraction of a molecule's kinetic energy in each cycle of the cooling sequence via a Sisyphus effect, allowing cooling with only a few repetitions of the dissipative decay process. We demonstrate the potential of optoelectrical cooling by reducing the temperature of about one million CH(3)F molecules by a factor of 13.5, with the phase-space density increased by a factor of 29 (or a factor of 70 discounting trap losses). In contrast to other cooling mechanisms, our scheme proceeds in a trap, cools in all three dimensions and should work for a large variety of polar molecules. With no fundamental temperature limit anticipated down to the photon-recoil temperature in the nanokelvin range, we expect our method to be able to produce ultracold polyatomic molecules. The low temperatures, large molecule numbers and long trapping times of up to 27 seconds should allow an interaction-dominated regime to be attained, enabling collision studies and investigation of evaporative cooling towards a Bose-Einstein condensate of polyatomic molecules.

Cavity Antiresonance Spectroscopy of Dipole Coupled Subradiant Arrays.

An array of N closely spaced dipole coupled quantum emitters exhibits super- and subradiance with characteristic tailorable spatial radiation patterns. Optimizing the emitter geometry and distance with respect to the spatial profile of a near resonant optical cavity mode allows us to increase the ratio between light scattering into the cavity mode and free space emission by several orders of magnitude. This leads to distinct scaling of the collective coherent emitter-field coupling vs the free space decay as a function of the emitter number. In particular, for subradiant states, the effective cooperativity increases much faster than the typical linear ∝N scaling for independent emitters. This extraordinary collective enhancement is manifested both in the amplitude and the phase profile of narrow collective antiresonances appearing at the cavity output port in transmission spectroscopy.

Impulsive Decision Making in Young Adult Social Drinkers and Detoxified Alcohol-Dependent Patients: A Cross-Sectional and Longitudinal Study.

BACKGROUND: Impulsive decision making relates to problematic substance use. Specifically, altered delay discounting (DD) has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting (PD) or loss aversion are clearly understudied. METHODS: Two studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of DD, PD for gains and losses, and loss aversion. Study (1): In a sample of 198 male 18-year-old social drinkers, we analyzed impulsive choice behavior and its association with alcohol consumption and self-report measures of substance use-related personality traits on a cross-sectional level. Additionally, the predictive value of baseline choice behavior for the trajectories of alcohol consumption over a 12-month follow-up period was evaluated. Study (2): Behavioral data on choice impulsivity were collected for 114 detoxified patients with alcohol use disorder (AUD) and 98 control participants. We analyzed group differences at baseline and assessed the predictive value of choice impulsivity for relapse to heavy alcohol use in patients during a follow-up period of 48 weeks. RESULTS: Study (1): Only DD was associated with baseline alcohol use, but no measure of choice impulsivity predicted the drinking trajectories over the following 12 months. Study (2): Compared to the control group, AUD patients showed higher DD, lower risk aversion regarding probabilistic gains, lower risk seeking regarding probabilistic losses, and lower loss aversion facing mixed prospects. Further, shallow discounting of probabilistic losses at baseline was predictive for relapse in patients. CONCLUSIONS: All 4 domains of impulsive decision making were considerably altered in AUD patients though mostly not related to alcohol use in young adult social drinkers. This suggests that these facets of impulsive behavior may develop as consequences of chronic alcohol consumption. Furthermore, discounting of probabilistic losses might prove valuable in identifying patients vulnerable for relapse.

Determining 3D Kinematics of the Hip Using Video Fluoroscopy: Guidelines for Balancing Radiation Dose and Registration Accuracy.

BACKGROUND: Video fluoroscopy is a technique currently used to retrieve the in vivo three-dimensional kinematics of human joints during activities of daily living. Minimization of the radiation dose absorbed by the subject during the measurement is a priority and has not been thoroughly addressed so far. This issue is critical for the motion analysis of the hip joint, because of the proximity of the gonads. The aims of this study were to determine the x-ray voltage and the irradiation angle that minimize the effective dose and to achieve the best compromise between delivered dose and accuracy in motion retrieval. METHODS: Effective dose for a fluoroscopic study of the hip was estimated by means of Monte Carlo simulations and dosimetry measurements. Accuracy in pose retrieval for the different viewing angles was evaluated by registration of simulated radiographs of a hip prosthesis during a prescribed virtual motion. RESULTS: Absorbed dose can be minimized to about one-sixth of the maximum estimated values by irradiating at the optimal angle of 45° from the posterior side and by operating at 80 kV. At this angle, accuracy in retrieval of internal-external rotation is poorer compared with the other viewing angles. CONCLUSION: The irradiation angle that minimizes the delivered dose does not necessarily correspond to the optimal angle for the accuracy in pose retrieval, for all rotations. For some applications, single-plane fluoroscopy may be a valid lower dose alternative to the dual-plane methods, despite their better accuracy.

Adolescent Women Induce Lower Blood Alcohol Levels Than Men in a Laboratory Alcohol Self-Administration Experiment.

BACKGROUND: Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive family history of alcoholism (FH), are often masked by environmental factors such as peer pressure. METHODS: We investigated how sex and FH modulate alcohol use in a sample of 18- to 19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults. Adolescents reported their real-life drinking in a TimeLine Follow-Back interview. They subsequently completed a training and an experimental session of free-access intravenous alcohol self-administration (i.v. ASA) using the computer-assisted alcohol infusion system to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at 8 time points. RESULTS: Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial blood alcohol concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the 2 sessions. CONCLUSIONS: We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm.

Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.

Multiscale optical simulation settings: challenging applications handled with an iterative ray-tracing FDTD interface method.

We show that with an appropriate combination of two optical simulation techniques-classical ray-tracing and the finite difference time domain method-an optical device containing multiple diffractive and refractive optical elements can be accurately simulated in an iterative simulation approach. We compare the simulation results with experimental measurements of the device to discuss the applicability and accuracy of our iterative simulation procedure.

Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers.

BACKGROUND: While the utility of experimental free-access alcohol self-administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. METHODS: Timeline Follow-back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self-administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a nonexposed age-matched control group of 42 (28 females, mean age 18.4 years) subjects. RESULTS: In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p < 0.05, respectively). In study 2, alcohol-exposed participants reported 7.1% and non-alcohol-exposed controls 6.5% fewer drinking days at poststudy measurement (p < 0.001), while percent heavy drinking days and drinks per drinking day did not differ. CONCLUSIONS: These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults.

Multiple interfacing between classical ray-tracing and wave-optical simulation approaches: a study on applicability and accuracy.

In this study the applicability of an interface procedure for combined ray-tracing and finite difference time domain (FDTD) simulations of optical systems which contain two diffractive gratings is discussed. The simulation of suchlike systems requires multiple FDTD↔RT steps. In order to minimize the error due to the loss of the phase information in an FDTD→RT step, we derive an equation for a maximal coherence correlation function (MCCF) which describes the maximum degree of impact of phase effects between these two different diffraction gratings and which depends on: the spatial distance between the gratings, the degree of spatial coherence of the light source and the diffraction angle of the first grating for the wavelength of light used. This MCCF builds an envelope of the oscillations caused by the distance dependent coupling effects between the two diffractive optical elements. Furthermore, by comparing the far field projections of pure FDTD simulations with the results of an RT→FDTD→RT→FDTD→RT interface procedure simulation we show that this function strongly correlates with the error caused by the interface procedure.