Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural ...circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses.
During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately.
BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation.
This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.
Psychotic disorders often develop a chronic course with devastating consequences for individuals, families, and societies. Early intervention programs for people in the first 5 years after the ...initial psychotic episode (early psychosis) can significantly improve the outcome and are therefore strongly recommended in national and international guidelines. However, most early intervention programs still focus on improving symptoms and relapse prevention, rather than targeting educational and vocational recovery. The aim of the present study is to explore the effects of Supported Employment and Education (SEE) following the Individual Placement and Support (IPS) model in people with early psychosis.
The SEEearly trial compares treatment as usual (TAU) plus SEE to TAU alone in outpatient psychiatric settings. The study is a six-site, two-arm, single-blinded, superiority randomized controlled trial (RCT). Participants are randomly assigned (1:1) to the intervention or control group. Aiming to recruit 184 participants, with an assumed drop-out rate of 22%, we will be able to detect a 24% difference in the main outcome of employment/education with 90% power. We make assessments at baseline and at 6- and 12-month follow-ups. Outcome data on employment/education, medication, and current psychiatric treatment is obtained monthly through phone based short assessments. The primary outcome is steady participation for at least 50% of the 12-month follow-up in competitive employment and/or mainstream education. Secondary employment outcomes capture length of employment/education, time to first employment/education, monthly wages/educational attainment, and social return on investment (SROI). Secondary non-employment outcomes include subjective quality of life, psychopathology, substance use, relapse, hospitalization, and functional impairment. To be eligible, participants must be between 16 and 35 years, fulfill diagnostic criteria for early psychosis, and be interested in competitive employment and/or mainstream education.
In SEEearly, we hypothesize that participants with psychosis, who receive TAU plus SEE, present with better primary and secondary outcomes than participants, who receive TAU alone. Positive results of this study will justify SEE as an evidence-based strategy for clinical routine treatment in people with early psychosis.
SEEearly was registered nationally and internationally in the German Clinical Trials Register (DRKS; identifier: DRKS00029660) on October 14, 2022.
Lissencephaly is a malformation of cortical development typically caused by deficient neuronal migration resulting in cortical thickening and reduced gyration. Here we describe a “thin” lissencephaly ...(TLIS) variant characterized by megalencephaly, frontal predominant pachygyria, intellectual disability, and seizures. Trio-based whole-exome sequencing and targeted re-sequencing identified recessive mutations of CRADD in six individuals with TLIS from four unrelated families of diverse ethnic backgrounds. CRADD (also known as RAIDD) is a death-domain-containing adaptor protein that oligomerizes with PIDD and caspase-2 to initiate apoptosis. TLIS variants cluster in the CRADD death domain, a platform for interaction with other death-domain-containing proteins including PIDD. Although caspase-2 is expressed in the developing mammalian brain, little is known about its role in cortical development. CRADD/caspase-2 signaling is implicated in neurotrophic factor withdrawal- and amyloid-β-induced dendritic spine collapse and neuronal apoptosis, suggesting a role in cortical sculpting and plasticity. TLIS-associated CRADD variants do not disrupt interactions with caspase-2 or PIDD in co-immunoprecipitation assays, but still abolish CRADD’s ability to activate caspase-2, resulting in reduced neuronal apoptosis in vitro. Homozygous Cradd knockout mice display megalencephaly and seizures without obvious defects in cortical lamination, supporting a role for CRADD/caspase-2 signaling in mammalian brain development. Megalencephaly and lissencephaly associated with defective programmed cell death from loss of CRADD function in humans implicate reduced apoptosis as an important pathophysiological mechanism of cortical malformation. Our data suggest that CRADD/caspase-2 signaling is critical for normal gyration of the developing human neocortex and for normal cognitive ability.
In this paper we present the first results on the template-assisted synthesis of lithium nanotubes from the ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide (Py1,4 TFSA). ...Lithium was electrochemically deposited from a 0.5molkg−1 LiTFSA in Py1,4 TFSA solution inside the pores of a copper-sputtered polycarbonate membrane. Afterwards the membrane was dissolved with THF and the samples were investigated by scanning electron microscopy (SEM). The results show the formation of partly free standing lithium nanotubes which form nanowires with increasing deposition time.
•Lithium has been electrodeposited inside of a track etched polycarbonate membrane.•Lithium preferentially grows at the interface membrane/ionic liquid from bottom up.•Lithium nanotubes form nanowires by closing the tube to a wire from the wall side.
We review the state of the art in the formulation, implementation, and performance of so-called high-order/low-order (HOLO) algorithms for challenging multiscale problems. HOLO algorithms attempt to ...couple one or several high-complexity physical models (the high-order model, HO) with low-complexity ones (the low-order model, LO). The primary goal of HOLO algorithms is to achieve nonlinear convergence between HO and LO components while minimizing memory footprint and managing the computational complexity in a practical manner. Key to the HOLO approach is the use of the LO representations to address temporal stiffness, effectively accelerating the convergence of the HO/LO coupled system. The HOLO approach is broadly underpinned by the concept of nonlinear elimination, which enables segregation of the HO and LO components in ways that can effectively use heterogeneous architectures. The accuracy and efficiency benefits of HOLO algorithms are demonstrated with specific applications to radiation transport, gas dynamics, plasmas (both Eulerian and Lagrangian formulations), and ocean modeling. Across this broad application spectrum, HOLO algorithms achieve significant accuracy improvements at a fraction of the cost compared to conventional approaches. It follows that HOLO algorithms hold significant potential for high-fidelity system scale multiscale simulations leveraging exascale computing.
Solvation Dynamics in Mixtures of Polar and Nonpolar Solvents Cichos, F; Willert, A; Rempel, U ...
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
10/1997, Volume:
101, Issue:
44
Journal Article
Peer reviewed
Time-resolved Stokes shift measurements and steady-state absorption and fluorescence measurements of Coumarin 153 (C153) at different temperatures were used to explore the solvation dynamics of ...binary mixtures of alcohols and alkanes at various alcohol concentrations. These solvent mixtures show even at alcohol concentrations as low as 0.3% a strong Stokes shift of about 1200 cm-1. Depending on alcohol concentration, this Stokes shift takes place on a time scale ranging from 300 ps up to several nanoseconds. These characteristic times are 2 orders of magnitude longer than the relaxation times typically found in alcohols, which is attributed to rotational reorientation of the solvent molecules. A monoexponential temporal behavior of the Stokes shift and a linear dependence of the time constants on the alkane viscosity are observed. These results and temperature dependent static fluorescence measurements strongly support a diffusion-controlled process of solvation in these mixtures.
Particle Image Velocimetry Raffel, Markus; Kompenhans, Jürgen; Wereley, Steve T ...
2007, 2007-09-14, 20070401
eBook
This practical guide to PIV provides in a condensed form most of the information relevant for the planning, performance and understanding of experiments employing the PIV technique. In its second ...edition, the authors updated the chapters on the principles and included information on microscopic, high-speed and three component measurements as well as a description of advanced evaluation techniques. Steve Wereley with his knowledge completed the group of authors of the first edition and his participation as an author was the key for that update. But also the drastic increase in the range of possible applications has been taken into account as the chapter describing representative applications of the PIV technique has been expanded considerably. The resulting book is mainly intended for engineers, scientists and students, who already have some basic knowledge of fluid mechanics and non-intrusive optical measurement techniques. For many researchers and engineers planning to utilize PIV for their special industrial or scientific applications, PIV is just an attractive tool with unique features which may help them to gain new insights in problems of fluid mechanics. These people are usually not interested in becoming specialists in this field before starting their investigations. On the other side some of the basic properties of PIV must be well understood before a correct interpretation of the results is possible.
Self-assembled triadic aggregates of porphyrins were formed from a covalently linked zinc-octaethyl-porphyrin dimer (ZnPD) and either of two different dipyridyl-substituted free base porphyrins, ...making use of the extra-ligation of zinc-porphyrin by the pyridyl-substituents of the free base porphyrins. The two free base porphyrins differ in the phenyl-substituents which are linked to them apart from the two pyridyl-groups. In one case these phenyl-substituents are pentafluorinated (H
2PF) while in the other case (H
2P) they are not. In the aggregate formed with H
2PF fluorescence quenching of both parts, ZnPD as well as H
2PF, indicates electron transfer from ZnPD to H
2PF which is effective down to 120
K. In the aggregate formed with H
2P the amount of population of the excited state H
2P is dependent on the solvent dielectric constant as well as on temperature. This is attributed to a close lying charge separated state which exchanges rapidly with the excited state of H
2P.
The Clinic for Special Children (CSC) has integrated biochemical and molecular methods into a rural pediatric practice serving Old Order Amish and Mennonite (Plain) children. Among the Plain people, ...we have used single nucleotide polymorphism (SNP) microarrays to genetically map recessive disorders to large autozygous haplotype blocks (mean = 4.4 Mb) that contain many genes (mean = 79). For some, uninformative mapping or large gene lists preclude disease-gene identification by Sanger sequencing. Seven such conditions were selected for exome sequencing at the Broad Institute; all had been previously mapped at the CSC using low density SNP microarrays coupled with autozygosity and linkage analyses. Using between 1 and 5 patient samples per disorder, we identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. Our results reveal the power of coupling new genotyping technologies to population-specific genetic knowledge and robust clinical data.
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