Determination and analysis of the productivity gap in a measured daywork system

Call number: LD2668 .T4 1979 H35Master of Scienc

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward-or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1Ractivation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability

Intense Electromagnetic Outbursts from Collapsing Hypermassive Neutron Stars

We study the gravitational collapse of a magnetized neutron star using a novel numerical approach able to capture both the dynamics of the star and the behavior of the surrounding plasma. In this approach, a fully general relativistic magnetohydrodynamics implementation models the collapse of the star and provides appropriate boundary conditions to a force-free model which describes the stellar exterior. We validate this strategy by comparing with known results for the rotating monopole and aligned rotator solutions and then apply it to study both rotating and non-rotating stellar collapse scenarios, and contrast the behavior with what is obtained when employing the electrovacuum approximation outside the star. The non-rotating electrovacuum collapse is shown to agree qualitatively with a Newtonian model of the electromagnetic field outside a collapsing star. We illustrate and discuss a fundamental difference between the force-free and electrovacuum solutions, involving the appearance of large zones of electric-dominated field in the vacuum case. This provides a clear demonstration of how dissipative singularities appear generically in the non-linear time-evolution of force-free fluids. In both the rotating and non-rotating cases, our simulations indicate that the collapse induces a strong electromagnetic transient. In the case of sub-millisecond rotation, the magnetic field experiences strong winding and the transient carries much more energy. This result has important implications for models of gamma-ray bursts.Comment: 28 pages, 20 figures (quality lowered to reduce sizes). Improved initial data and matching condition results in a lower, but still important, energy emission. Added appendix with a discussion on effects of transition laye

Simultaneous MQMAS NMR experiments for two half-integer quadrupolar nuclei

A procedure to acquire two Multiple-Quantum Magic Angle Spinning (MQMAS) NMR experiments with the same instrument time is presented. A triply tuned probe is utilized with multiple receivers to collect data with staggered acquisitions and thus more efficiently use the instrument time. The data for one nucleus is collected during the recovery delay of the other nucleus, and vice versa. The instrument time is reduced to 60-80% of the time needed for the single acquisition collection Specifically our approach is presented for recording triple-quantum (3Q) 17O and either 3Q or quintuple-quantum (5Q) 27Al MAS NMR spectra of a 1.18Na2O•5SiO2•Al2O3 glass gel

Digital multiplex ligation assay for highly multiplexed screening of β-lactamase-encoding genes in bacterial isolates

Increasing incidence of antibiotic resistance in clinical and environmental settings calls for increased scalability in their surveillance. Current screening technologies are limited by the number of samples and genes that can easily be screened. We demonstrate here digital multiplex ligation assay (dMLA) as a low-cost targeted genomic detection workflow capable of highly-parallel screening of bacterial isolates for multiple target gene regions simultaneously. Here, dMLA is used for simultaneous detection of 1187 β-lactamase-encoding genes, including extended spectrum β-lactamase (ESBL) genes, in 74 bacterial isolates. We demonstrate dMLA as a light-weight and cost-efficient workflow which provides a highly scalable tool for antimicrobial resistance surveillance and is also adaptable to genetic screening applications beyond antibiotic resistance

Insensitivity to future consequences following damage to human prefrontal cortex.

Abstract Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes

Sidestream Smoke Extracts from Harm-Reduction and Conventional Camel Cigarettes Inhibit Osteogenic Differentiation via Oxidative Stress and Differential Activation of intrinsic Apoptotic Pathways

Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke being more harmful to developing cells than mainstream smoke. Furthermore, first reports are emerging to suggest a differential impact of conventional versus harm-reduction tobacco products on bone tissue as it develops in the embryo or in vitro. To gather first insight into the molecular mechanism of such differences, we assessed the effect of sidestream smoke solutions from Camel (conventional) and Camel Blue (harm-reduction) cigarettes using a human embryonic stem cell osteogenic differentiation model. Sidestream smoke from the conventional Camel cigarettes concentration-dependently inhibited in vitro calcification triggered by high levels of mitochondrially generated oxidative stress, loss of mitochondrial membrane potential, and reduced ATP production. Camel sidestream smoke also induced DNA damage and caspase 9-dependent apoptosis. Camel Blue-exposed cells, in contrast, invoked only intermediate levels of reactive oxygen species insufficient to activate caspase 3/7. Despite the absence of apoptotic gene activation, damage to the mitochondrial phenotype was still noted concomitant with activation of an anti-inflammatory gene signature and inhibited mineralization. Collectively, the presented findings in differentiating pluripotent stem cells imply that embryos may exhibit low bone mineral density if exposed to environmental smoke during development

L-theanine prevents long-term affective and cognitive side effects of adolescent Δ-9-tetrahydrocannabinol exposure and blocks associated molecular and neuronal abnormalities in the mesocorticolimbic circuitry

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-Theanine is an amino acid analog of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exposure in male rats, we report that L-theanine pretreatment before adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect that persists into adulthood. In addition, pretreatment with L-theanine blocked THC-induced downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and subcortical DAergic dysregulation. Finally, L-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of L-theanine in the mesocorticolimbic system

Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen

Y-box protein (YB)-1 of the cold-shock protein family functions in gene transcription and RNA processing. Extracellular functions have not been reported, but the YB-1 staining pattern in inflammatory glomerular diseases, without adherence to cell boundaries, suggests an extracellular occurrence. Here, we show the secretion of YB-1 by mesangial and monocytic cells after inflammatory challenges. It should be noted that YB-1 was secreted through a non-classical mode resembling that of the macrophage migration inhibitory factor. YB-1 release requires ATP-binding cassette transporters, and microvesicles protect YB-1 from protease degradation. Two lysine residues in the YB-1 carboxy-terminal domain are crucial for its release, probably because of post-translational modifications. The addition of purified recombinant YB-1 protein to different cell types results in increased DNA synthesis, cell proliferation and migration. Thus, the non-classically secreted YB-1 has extracellular functions and exerts mitogenic as well as promigratory effects in inflammation