277 research outputs found
Harnessing entropy to enhance toughness in reversibly crosslinked polymer networks
Reversible crosslinking is a design paradigm for polymeric materials, wherein
they are microscopically reinforced with chemical species that form transient
crosslinks between the polymer chains. Besides the potential for self-healing,
recent experimental work suggests that freely diffusing reversible crosslinks
in polymer networks, such as gels, can enhance the toughness of the material
without substantial change in elasticity. This presents the opportunity for
making highly elastic materials that can be strained to a large extent before
rupturing. Here, we employ Gaussian chain theory, molecular simulation, and
polymer self-consistent field theory for networks to construct an equilibrium
picture for how reversible crosslinks can toughen a polymer network without
affecting its linear elasticity. Maximisation of polymer entropy drives the
reversible crosslinks to bind preferentially near the permanent crosslinks in
the network, leading to local molecular reinforcement without significant
alteration of the network topology. In equilibrium conditions, permanent
crosslinks share effectively the load with neighbouring reversible crosslinks,
forming multi-functional crosslink points. The network is thereby globally
toughened, while the linear elasticity is left largely unaltered. Practical
guidelines are proposed to optimise this design in experiment, along with a
discussion of key kinetic and timescale considerations
Exact mean field inference in asymmetric kinetic Ising systems
We develop an elementary mean field approach for fully asymmetric kinetic
Ising models, which can be applied to a single instance of the problem. In the
case of the asymmetric SK model this method gives the exact values of the local
magnetizations and the exact relation between equal-time and time-delayed
correlations. It can also be used to solve efficiently the inverse problem,
i.e. determine the couplings and local fields from a set of patterns, also in
cases where the fields and couplings are time-dependent. This approach
generalizes some recent attempts to solve this dynamical inference problem,
which were valid in the limit of weak coupling. It provides the exact solution
to the problem also in strongly coupled problems. This mean field inference can
also be used as an efficient approximate method to infer the couplings and
fields in problems which are not infinite range, for instance in diluted
asymmetric spin glasses.Comment: 10 pages, 7 figure
The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus
The maternal separation paradigm has been applied to C57BL/6J mice as an animal developmental model for understanding structural deficits leading to abnormal behaviour. A maternal separation (MS) model was used on postnatal day (PND) 9, where the pups were removed from their mother for 24 h (MS24). When the pups were 10 weeks old, the level of anxiety and fear was measured with two behavioural tests; an open field test and an elevated plus maze test. The Barnes platform maze was used to test spatial learning, and memory by using acquisition trials followed by reverse trial sessions. The MS24 mice spent more time in the open arms of the elevated plus maze compared to controls, but no other treatment differences were found in the emotional behavioural tests. However, in the reverse trial for the Barnes maze test there was a significant difference in the frequency of visits to the old goal, the number of errors made by the MS24 mice compared to controls and in total distance moved. The mice were subsequently sacrificed and the total number of neurons estimated in the hippocampus using the optical fractionator. We found a significant loss of neurons in the dentate gyrus in MS mice compared to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology
Identification of Genetic and Epigenetic Variations in a Rat Model for Neurodevelopmental Disorders
A combination of genetic variations, epimutations and environmental factors may be involved in the etiology of complex neurodevelopmental disorders like schizophrenia. To study such disorders, we use apomorphine-unsusceptible (APO-UNSUS) Wistar rats and their phenotypic counterpart apomorphine-susceptible (APO-SUS) rats that display a complex phenotype remarkably similar to that of schizophrenic patients. As the molecular basis of the APO-SUS/UNSUS rat model, we recently identified a genomic rearrangement of the Aph-1b gene. Here, we discovered between the two rat lines differences other than the Aph-1b gene defect, including a remarkable cluster of genetic variations, two variants corresponding to topoisomerase II-based recombination hot spots and an epigenetic (DNA methylation) difference in cerebellum and (hypo)thalamic but not hippocampal genomic DNA. Furthermore, genetic variations were found to correlate with the degree of apomorphine susceptibility in unselected Wistar rats. Together, the results show that a number of genetic and epigenetic differences exist between the APO-SUS and -UNSUS rat genomes, raising the possibility that in addition to the Aph-1b gene defect the newly identified variations may also contribute to the complex APO-SUS phenotype
Origin of Corrections to Mean-field at the Onset of Unjamming
We present a detailed analysis of the unjamming transition in 2D frictionless
disk packings using a static correlation function that has been widely used to
study disordered systems. We show that this point-to-set (PTS) correlation
function exhibits a dominant length scale that diverges as the unjamming
transition is approached through decompression. In addition, we identify
deviations from meanfield predictions, and present detailed analysis of the
origin of non-meanfield behavior. A mean-field bulk-surface argument is
reviewed. Corrections to this argument are identified, which lead to a change
in the functional form of the critical PTS boundary size. An entropic
description of the origin of the correlations is presented, and simple rigidity
assumptions are shown to predict the functional form of the critical PTS
boundary size as a function of the pressure
The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders
Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders
Effect of apomorphine on cognitive performance and sensorimotor gating in humans
Contains fulltext :
88792.pdf (publisher's version ) (Closed access)INTRODUCTION: Dysfunction of brain dopamine systems is involved in various neuropsychiatric disorders. Challenge studies with dopamine receptor agonists have been performed to assess dopamine receptor functioning, classically using the release of growth hormone (GH) from the hindbrain as primary outcome measure. The objective of the current study was to assess dopamine receptor functioning at the forebrain level. METHODS: Fifteen healthy male volunteers received apomorphine sublingually (2 mg), subcutaneously (0.005 mg/kg), and placebo in a balanced, double-blind, cross-over design. Outcome measures were plasma GH levels, performance on an AX continuous performance test, and prepulse inhibition of the acoustic startle. The relation between central outcome measures and apomorphine levels observed in plasma and calculated in the brain was modeled using a two-compartmental pharmacokinetic-pharmacodynamic analysis. RESULTS: After administration of apomorphine, plasma GH increased and performance on the AX continuous performance test deteriorated, particularly in participants with low baseline performance. Apomorphine disrupted prepulse inhibition (PPI) on high-intensity (85 dB) prepulse trials and improved PPI on low intensity (75 dB) prepulse trials, particularly in participants with low baseline PPI. High cognitive performance at baseline was associated with reduced baseline sensorimotor gating. Neurophysiological measures correlated best with calculated brain apomorphine levels after subcutaneous administration. CONCLUSION: The apomorphine challenge test appears a useful tool to assess dopamine receptor functioning at the forebrain level. Modulation of the effect of apomorphine by baseline performance levels may be explained by an inverted U-shape relation between prefrontal dopamine functioning and cognitive performance, and mesolimbic dopamine functioning and sensorimotor gating. Future apomorphine challenge tests preferentially use multiple outcome measures, after subcutaneous administration of apomorphine.1 januari 201
Societal output and use of research performed by health research groups
The last decade has seen the evaluation of health research pay more and more attention to societal use and benefits of research in addition to scientific quality, both in qualitative and quantitative ways. This paper elaborates primarily on a quantitative approach to assess societal output and use of research performed by health research groups (societal quality of research). For this reason, one of the Dutch university medical centres (i.e. the Leiden University Medical Center (LUMC)) was chosen as the subject of a pilot study, because of its mission to integrate top patient care with medical, biomedical and healthcare research and education. All research departments were used as units of evaluation within this university medical centre
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