917 research outputs found

    A Theoretical Analysis of Two-Stage Recommendation for Cold-Start Collaborative Filtering

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    In this paper, we present a theoretical framework for tackling the cold-start collaborative filtering problem, where unknown targets (items or users) keep coming to the system, and there is a limited number of resources (users or items) that can be allocated and related to them. The solution requires a trade-off between exploitation and exploration as with the limited recommendation opportunities, we need to, on one hand, allocate the most relevant resources right away, but, on the other hand, it is also necessary to allocate resources that are useful for learning the target's properties in order to recommend more relevant ones in the future. In this paper, we study a simple two-stage recommendation combining a sequential and a batch solution together. We first model the problem with the partially observable Markov decision process (POMDP) and provide an exact solution. Then, through an in-depth analysis over the POMDP value iteration solution, we identify that an exact solution can be abstracted as selecting resources that are not only highly relevant to the target according to the initial-stage information, but also highly correlated, either positively or negatively, with other potential resources for the next stage. With this finding, we propose an approximate solution to ease the intractability of the exact solution. Our initial results on synthetic data and the Movie Lens 100K dataset confirm the performance gains of our theoretical development and analysis

    Age related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal

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    Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats

    Mechanistic and Functional Divergence Between Thyrotropin-releasing Hormone and RO 15-4513 Interactions with Ethanol

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    Both thyrotropin-releasing hormone (TRH) and RO 15-4513 antagonize ethanol-induced depression, but this common property does not infer that both compounds share similar mechanisms of action. In the present studies, both TRH (30 mg/kg, i.p.) and RO 15-4513 (10 mg/kg, i.p.) reversed ethanol-induced depression of locomotor activity, in accord with previous reports. However, the benzodiazepine antagonist, RO 15-1788, blocked this action of RO 15-4513, while exerting no effect on the analeptic action of TRH. Using a model of seizure activity electrically elicited from the inferior colliculus, ethanol exerted a dose-related attenuation of seizure activity. This anticonvulsant action of ethanol was not altered by TRH (30 mg/kg, i.p.), but RO 15-4513 (3 mg/kg) reversed the effect of the 0.5, but not the 1.0 g/kg, dose of ethanol. In addition, pretreatment with RO 15-4513 (1 or 3 mg/kg, i.p.), but not TRH (30 mg/kg, i.p.), caused seizure generalization into the forebrain following inferior collicular stimulation, further verifying the proconvulsant properties of RO 15-4513. In conclusion, the analeptic action of TRH appears independent of benzodiazepine activity, and in contrast to RO 15-4513, TRH does not exhibit proconvulsant properties. Furthermore, because TRH did not antagonize both depressant actions of ethanol studied, it appears unlikely that TRH directly interacts with the molecular basis of ethanol action

    Persistent adaptation by chronic alcohol is facilitated by neuroimmune activation linked to stress and CRF

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    This review updates the conceptual basis for the association of alcohol abuse with an insidious adaptation that facilitates negative affect during withdrawal from chronic intermittent alcohol (CIA) exposure – a change that later supports sensitization of stress-induced anxiety following alcohol abstinence. The finding that a CRF1-receptor antagonist (CRF1RA) minimized CIA withdrawal-induced negative affect supported an association of alcohol withdrawal with a stress mechanism. The finding that repeated stresses or multiple CRF injections into selected brain sites prior to a single 5-day chronic alcohol (CA) exposure induced anxiety during withdrawal provided critical support for a linkage of CIA withdrawal with stress. The determination that CRF1RA injection into positive CRF-sensitive brain sites prevented CIA withdrawal-induced anxiety provided support that neural path integration maintains the persistent CIA adaptation. Based upon reports that stress increases neuroimmune function, an effort was undertaken to test whether cytokines would support the adaptation induced by stress/CA exposure. Twenty-four hours after withdrawal from CIA, cytokine mRNAs were found to be increased in cortex as well as other sites in brain. Further, repeated cytokine injections into previously identified brain sites substituted for stress and CRF induction of anxiety during CA withdrawal. Discovery that a CRF1RA prevented the brain cytokine mRNA increase induced by CA withdrawal provided critical evidence for CRF involvement in this neuroimmune induction after CA withdrawal. However, the CRF1RA did not block the stress increase in cytokine mRNA increases in controls. The latter data supported the hypothesis that distinct mechanisms linked to stress and CA withdrawal can support common neuroimmune functions within a brain site. As evidence evolves concerning neural involvement in brain neuroimmune function, a better understanding of the progressive adaptation associated with CIA exposure will advance new knowledge that could possibly lead to strategies to combat alcohol abuse

    A mouse model for chronic pain-induced increase in ethanol consumption

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    Chronic pain conditions are often co-morbid with alcohol abuse. “Self-medication” with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the co-morbid conditions are lacking. In the present study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham operated mice served as controls. Thirteen weeks after surgery, DMM but not sham operated mice exhibited pronounced incapacitance of the surgically-manipulated hindlimb compared to the non-surgically manipulated hindlimb. At this time, the mice were exposed to the two-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared to sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared to sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the co-morbid association of alcohol abuse and chronic pain conditions can be explored

    Drug Challenges Reveal Differences in Mediation of Stress Facilitation of Voluntary Alcohol Drinking and Withdrawal-Induced Anxiety in Alcohol-Preferring P Rats

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    There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety

    Modulation of Ethanol Withdrawal???Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/??-Aminobutyric Acid Ligands

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    Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal

    Withdrawal from Chronic Alcohol Induces a Unique CCL2 mRNA Increase in Adolescent But Not Adult Brain-Relationship to Blood Alcohol Levels and Seizures

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    The role of neuroimmune activation in withdrawal from chronic alcohol (ethanol) has been established in both adolescent and adult models, but direct comparisons across age are sparse. Studies need to elucidate age-dependent neuroimmune effects of alcohol and to focus research attention on age-dependent mechanisms and outcomes

    Accentuated Decrease in Social Interaction in Rats Subjected to Repeated Ethanol Withdrawals

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    Previous work has shown that repeated withdrawals from chronic ethanol exposure can kindle seizures in rodents. In this article, the effects of a three-cycle model of ethanol exposure and withdrawal on the social interaction test of anxiety are summarized

    Baclofen Blocks Expression and Sensitization of Anxiety-Like Behavior in an Animal Model of Repeated Stress and Ethanol Withdrawal

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    Repeated exposures to forced ethanol diets (EDs) or restraint stress sensitize anxiety-like behavior during a future ethanol withdrawal. The present investigation assessed whether pretreatment of rats with agents targeting receptor systems thought to be important in treating relapse in alcoholic patients would prevent sensitization of anxiety-like behavior
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