Disrupted GABAergic facilitation of working memory performance in people with schizophrenia.

ObjectivesGamma-Amiobutyric acid (GABA) is a primary inhibitory neurotransmitter that facilitates neural oscillations that coordinate neural activity between brain networks to facilitate cognition. The present magnetic resonance spectroscopy (MRS) study tests the hypothesis that GABAergic facilitation of working memory is disrupted in people with schizophrenia (PSZ).Methods51 healthy participants and 40 PSZ from the UC Davis Early Psychosis Program performed an item and temporal order working memory (WM) task and underwent resting MRS to measure GABA and glutamate concentrations in dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) regions of interest. MRS was acquired on a 3 Tesla Siemens scanner and GABA and glutamate concentrations were referenced to creatine. Percent correct on the WM task indexed performance and correlation coefficients examined GABAergic or Glutamatergic facilitation of WM, with Fisher's Z transformation testing for group differences.ResultsThere were no group differences in GABA or glutamate concentrations, but WM correlations were reversed between groups. In patients, higher DLPFC GABA was associated with worse rather than better WM performance. This pattern was not observed for glutamate or in the ACC. Although under-powered, there was no indication of medication effects.Conclusions and relevanceResults cannot be explained by group differences in DLPFC GABA or glutamate concentrations but, instead, indicate that schizophrenia disrupts the GABAergic facilitation of WM seen in healthy individuals. Results appear to parallel post mortem findings in suggesting that schizophrenia alters the distribution of different classes of GABAergic interneurons rather than producing a general deficit across the total population of neurons

Control dependence for extended finite state machines

Though there has been nearly three decades of work on program slicing, there has been comparatively little work on slicing for state machines. One of the primary challenges that currently presents a barrier to wider application of state machine slicing is the problem of determining control dependence. We survey existing related definitions, introducing a new definition that subsumes one and extends another. We illustrate that by using this new definition our slices respect Weiser slicing’s termination behaviour. We prove results that clarify the relationships between our definition and older ones, following this up with examples to motivate the need for these differences

A Numerical Model Study for Development of a Harbour Layout in a Creek with Wide Tidal Flat

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Learning Invariant Representations with Missing Data

Spurious correlations allow flexible models to predict well during training but poorly on related test distributions. Recent work has shown that models that satisfy particular independencies involving correlation-inducing \textit{nuisance} variables have guarantees on their test performance. Enforcing such independencies requires nuisances to be observed during training. However, nuisances, such as demographics or image background labels, are often missing. Enforcing independence on just the observed data does not imply independence on the entire population. Here we derive \acrshort{mmd} estimators used for invariance objectives under missing nuisances. On simulations and clinical data, optimizing through these estimates achieves test performance similar to using estimators that make use of the full data.Comment: CLeaR (Causal Learning and Reasoning) 202

Impaired recollection of visual scene details in adults with autism spectrum conditions.

Subtle memory deficits observed in autism spectrum conditions (ASC) have often been characterized as reflecting impaired recollection and it has been proposed that a relational binding deficit may underlie the recollection impairment. However, subjective recollection and relational binding have not been measured within the same task in ASC to date and it is unclear whether a relational binding deficit can provide a full account of recollection impairments in ASC. Relational memory has also not been compared with item memory when the demands of the 2 tasks are comparable. To assess recollection, relational memory, and item memory within a single task in ASC, 24 adults with ASC and 24 typically developed adults undertook a change detection memory task that assessed recollection of item-specific and spatial details. Participants studied rendered indoor and outdoor scenes and, in a subsequent recognition memory test, distinguished scenes that had not changed from those that had either undergone an item change (a different item exemplar) or a relational (spatial) change, which was followed by a subjective recollection judgment. The ASC group identified fewer item changes and spatial changes, to a similar degree, which was attributable to a specific reduction in recollection-based recognition relative to the control group. These findings provide evidence that recollection deficits in ASC may not be driven entirely by a relational binding deficit.This research was supported by a James S. McDonnell Scholar Award to J.S.S., an Economic and Social Research Council Award to R.A.C., and Leverhulme Trust Visiting Professorship and Parke Davis Exchange Fellowship Awards to C.R.This is the author accepted manuscript. The final version is available from he American Psychological Association via http://dx.doi.org/10.1037/abn000007

Pheromone Trapping Protocols for Brinjal Shoot and Fruit Borer, Leucinodes orbonalis Guenee (Lepidoptera: Pyralidae): Evaluation of Trap Design, Quantity and Dispenser

Studies were conducted at the Indian Institute of Horticultural Research, Bangalore, and Central Horticultural Experiment Station, Bhubaneshwar, India, to evaluate trap design, quantity of pheromone loading and dispensers for attracting brinjal shoot and fruit borer, Leucinodes orbonalis Guenee (Lepidoptera: Pyralidae) using indigenously synthesized pheromone lure [synthesized by Indian Institute of Chemical Technology (IICT), Hyderabad], during 2003 and 2004. A water trap consisting of plastic container (20 cm dia. and 7.5 cm depth) with a facility to place the pheromone septum was designed. Pheromone load of 4 mg in both water trap and Pest Control India (PCI®) delta trap was observed to catch higher number of male moths compared to dispensers with lesser loading. When trap designs were compared, water trap with pheromone lure was observed to attract higher number of males than Pest Control India (PCI®) delta trap. Among the different pheromone dispensers tested, rubber septum was superior to plastic vial or plastic septum. Rubber septum supplied by Bio Pest Management® captured significantly higher number of moths compared to rubber and plastic septum supplied by difTerent firms. A comparison of IICT synthesized lures along with some commercially available lures indicated that Bio Pest Management® lure dispensed in rubber outperformed PCI® and IICT lures

Force and temperature analysis during distinct machining environment using an optimization approach

Cryogenic cooling with liquid nitrogen has a wide field of scientific and engineering applications. The aim of the presented research work is to analyze the impact on cutting force and temperature during the LN2 single supply at (i) rake face and double supply (ii) rake and flank face of TiN coated carbide cutting tool during turning of AISI D3 steel. Taguchi based S/N ratio was used for Design of Experiments (DoE) of L18 orthogonal array. The four control factors were selected.The three factors like speed, feed and depth of cut were varied to three levels. The fourth factor was the machining condition which was varied to two levels. The cutting force and temperature were declined by 32-48% and 34-46% during the double supply of LN2 at rake and flank face as compared to single supply at rake face. The influence and percentage of contribution of each factor were found out by Analysis of Variance (ANOVA). The double supply method with LN2 supply at rake and flank face had the highest effect of contribution in the percentage as 77.13% and 87.42% for cutting force and temperature respectively. The values obtained during confirmatory runs were very close to the optimized results within the limits

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

Objective: In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. Methods: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. Results: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). Conclusions: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs

The influence of spatial pattern on visual short-term memory for contrast

Several psychophysical studies of visual short-term memory (VSTM) have shown high-fidelity storage capacity for many properties of visual stimuli. On judgments of the spatial frequency of gratings, for example, discrimination performance does not decrease significantly, even for memory intervals of up to 30 s. For other properties, such as stimulus orientation and contrast, however, such “perfect storage” behavior is not found, although the reasons for this difference remain unresolved. Here, we report two experiments in which we investigated the nature of the representation of stimulus contrast in VSTM using spatially complex, two-dimensional random-noise stimuli. We addressed whether information about contrast per se is retained during the memory interval by using a test stimulus with the same spatial structure but either the same or the opposite local contrast polarity, with respect to the comparison (i.e., remembered) stimulus. We found that discrimination thresholds got steadily worse with increasing duration of the memory interval. Furthermore, performance was better when the test and comparison stimuli had the same local contrast polarity than when they were contrast-reversed. Finally, when a noise mask was introduced during the memory interval, its disruptive effect was maximal when the spatial configuration of its constituent elements was uncorrelated with those of the comparison and test stimuli. These results suggest that VSTMfor contrast is closely tied to the spatial configuration of stimuli and is not transformed into a more abstract representation

Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes