Sequential presentation protects working memory from catastrophic interference

Neural network models of memory are notorious for catastrophic interference: old items are forgotten as new items are memorized (e.g., French, 1999; McCloskey & Cohen, 1989). While Working Memory (WM) in human adults shows severe capacity limitations, these capacity limitations do not reflect neural-network style catastrophic interference. However, our ability to quickly apprehend the numerosity of small sets of objects (i.e., subitizing) does show catastrophic capacity limitations, and this subitizing capacity and WM might reflect a common capacity. Accordingly, computational investigations (Knops, Piazza, Sengupta, Eger, & Melcher, 2014; Sengupta, Surampudi, & Melcher, 2014) suggest that mutual inhibition among neurons can explain both kinds of capacity limitations as well as why our ability to estimate the numerosity of larger sets is limited according to a Weber ratio signature. Based on simulations with a saliency map-like network and mathematical proofs, we provide three results. First, mutual inhibition among neurons leads to catastrophic interference when items are presented simultaneously. The network can remember a limited number of items, but when more items are presented, the network forgets all of them. Second, if memory items are presented sequentially rather than simultaneously, the network remembers the most recent items rather than forgetting all of them. Hence, the tendency in WM tasks to sequentially attend even to simultaneously presented items might not only reflect attentional limitations, but an adaptive strategy to avoid catastrophic interference. Third, the mean activation level in the network can be used to estimate the number of items in small sets, but does not accurately reflect the number of items in larger sets. Rather, we suggest that the Weber ratio signature of large number discrimination emerges naturally from the interaction between the limited precision of a numeric estimation system and a multiplicative gain control mechanism

Analysis of a microscopic stochastic model of microtubule dynamic instability

A novel theoretical model of dynamic instability of a system of linear (1D) microtubules (MTs) in a bounded domain is introduced for studying the role of a cell edge in vivo and analyzing the effect of competition for a limited amount of tubulin. The model differs from earlier models in that the evolution of MTs is based on the rates of single unit (e.g., a heterodimer per protofilament) transformations, in contrast to postulating effective rates/frequencies of larger-scale changes, extracted, e.g., from the length history plots of MTs. Spontaneous GTP hydrolysis with finite rate after polymerization is assumed, and theoretical estimates of an effective catastrophe frequency as well as other parameters characterizing MT length distributions and cap size are derived. We implement a simple cap model which does not include vectorial hydrolysis. We demonstrate that our theoretical predictions, such as steady state concentration of free tubulin, and parameters of MT length distributions, are in agreement with the numerical simulations. The present model establishes a quantitative link between microscopic parameters governing the dynamics of MTs and macroscopic characteristics of MTs in a closed system. Lastly, we use a computational Monte Carlo model to provide an explanation for non-exponential MT length distributions observed in experiments. In particular, we show that appearance of such non-exponential distributions in the experiments can occur because the true steady state has not been reached, and/or due to the presence of a cell edge.Comment: 14 pages, 7 figure

Yhteisön intressien ja tutkimustavoitteiden integroiminen yhteisötoimintatutkimuksissa

Summary: Community action research projects: integrating community interests and research agenda in multicomponent iniatives

Equilibria of Idealized Confined Astral Microtubules and Coupled Spindle Poles

Positioning of the mitotic spindle through the interaction of astral microtubules with the cell boundary often determines whether the cell division will be symmetric or asymmetric. This process plays a crucial role in development. In this paper, a numerical model is presented that deals with the force exerted on the spindle by astral microtubules that are bent by virtue of their confinement within the cell boundary. It is found that depending on parameters, the symmetric position of the spindle can be stable or unstable. Asymmetric stable equilibria also exist, and two or more stable positions can exist simultaneously. The theory poses new types of questions for experimental research. Regarding the cases of symmetric spindle positioning, it is necessary to ask whether the microtubule parameters are controlled by the cell so that the bending mechanics favors symmetry. If they are not, then it is necessary to ask what forces external to the microtubule cytoskeleton counteract the bending effects sufficiently to actively establish symmetry. Conversely, regarding the cases with asymmetry, it is now necessary to investigate whether the cell controls the microtubule parameters so that the bending favors asymmetry apart from any forces that are external to the microtubule cytoskeleton

The "Clubs against Drugs" program in Stockholm, Sweden: two cross-sectional surveys examining drug use among staff at licensed premises

<p>Abstract</p> <p>Background</p> <p>The objective of this study is to examine self-reported drug use among staff at licensed premises, types of drugs used, attitudes towards drugs, and observed drug use among guests. Results are presented from two measurement points (in 2001 and 2007/08). This study was carried out within the framework of the "Clubs against Drugs" program, which is a community-based multi-component intervention targeting licensed premises in Stockholm, Sweden.</p> <p>Methods</p> <p>Two cross-sectional surveys were conducted, the first in 2001 and the second in 2007/08. Staff at licensed premises attending server training were asked to participate in the anonymous survey. A survey was administered in a classroom setting and consisted of four sections: 1) demographics, 2) respondents' own drug use experience, 3) respondents' attitudes towards drug use, and 4) observed drug use among guests at licensed premises.</p> <p>Results</p> <p>Data were collected from 446 staff in 2001 and 677 staff in 2007/08. The four most commonly used drugs among staff were cannabis, cocaine, amphetamine, and ecstasy. The highest rates of drug use were reported by staff in the two youngest age groups, i.e., those younger than 25 and those between the ages of 25 and 29. In 2007/08 staff reported significantly lower rates of drug use than staff in 2001. Last year drug use for the sample in 2007/08 was 19% compared to 27% for the 2001 sample. While drug-using staff compared to non drug-using staff reported more observations of drug use among guests, they were less inclined to intervene. Overall, staff reported restrictive attitudes towards drugs.</p> <p>Conclusions</p> <p>The prevalence of life-time and last year drug use among staff at licensed premises is high compared to the general population in Sweden. Lower rates of self-reported drug use among staff were reported in 2007/08. The results of this study highlight that staff at licensed premises represent an important target population in club drug prevention programs.</p

Measuring substance use in the club setting: a feasibility study using biochemical markers

<p>Abstract</p> <p>Background</p> <p>During the last few decades the use of club drugs (e.g., cocaine, amphetamines) has been of increased concern in nightlife settings. Traditionally, surveys have been used to estimate the use of club drugs, however, they mostly rely on self-reports which may not be accurate. Recent advances have allowed for readily accessible drug testing methods such as oral fluid drug testing. Nevertheless, research using oral fluid sampling to measure the frequency of drug use in the club environment is scarce. The objective of this study is to evaluate the feasibility of measuring the frequency of alcohol and drug use among Swedish clubbers using breath alcohol and oral fluid drug testing.</p> <p>Method</p> <p>The setting was a 40 hour electronic music dance event (EMDE) on a cruise ship on the Baltic Sea, departing from Sweden, with 875 passengers. Groups of participants at the EMDE were randomly invited to participate. Data were collected with face-to-face and self-administered questionnaires. Further, oral fluid samples were collected to determine illicit drug use, and blood alcohol concentration (BAC) levels were measured using a breath analyzer.</p> <p>Results</p> <p>A total of 422 passengers were asked to participate in the study whereof 21 declined (5.0% refusal rate). Of the 401 study participants (accounting for 45.8% of all attendees), 5 declined oral fluid drug testing. Results show that there was a discrepancy between self-reported and actual drug use as 10.1% of the participants were positive on illicit drug use (amphetamines, ecstasy/MDMA, cannabis, cocaine), while only 3.7% of the participants reported drug use during the last 48 hours. The average BAC level was 0.10% and 23.7% had BAC levels ≥ 0.15%, while 5.9% had levels below the detection limit. The mean BAC levels for the illicit drug users were significantly higher (<it>p </it>= 0.004) than for non-drug users (0.13% vs. 0.10%). Self-reported AUDIT-C scores (using a threshold of ≥ 5 for men and ≥ 4 for women) revealed that 76.0% of the men and 80.7% of the women had risky alcohol consumption patterns.</p> <p>Conclusion</p> <p>This study indicates that it is feasible to conduct breath alcohol and oral fluid drug testing in a Swedish club setting.</p

Efficiency of Organelle Capture by Microtubules as a Function of Centrosome Nucleation Capacity: General Theory and the Special Case of Polyspermia

Transport of organelles along microtubules is essential for the cell metabolism and morphogenesis. The presented analysis derives the probability that an organelle of a given size comes in contact with the microtubule aster. The question is asked how this measure of functionality of the microtubule aster is controlled by the centrosome. A quantitative model is developed to address this question. It is shown that for the given set of cellular parameters, such as size and total tubulin content, a centrosome nucleation capacity exists that maximizes the probability of the organelle capture. The developed general model is then applied to the capture of the female pronucleus by microtubules assembled on the sperm centrosome, following physiologically polyspermic fertilization. This application highlights an unintuitive reflection of nonlinearity of the nucleated polymerization of the cellular pool of tubulin. The prediction that the sperm centrosome should lower its nucleation capacity in the face of the competition from the other sperm is a stark illustration of the new optimality principle. Overall, the model calls attention to the capabilities of the centrosomal pathway of regulation of the transport-related functionality of the microtubule cytoskeleton. It establishes a quantitative and conceptual framework that can guide experiment design and interpretation

Underuse of medication for circulatory disorders among unmarried women and men in Norway?

BACKGROUND: It is well established that unmarried people have higher mortality from circulatory diseases and higher all-cause mortality than the married, and these marital status differences seem to be increasing. However, much remains to be known about the underlying mechanisms. Our objective was to examine marital status differences in the purchase of medication for circulatory diseases, and risk factors for them, which may indicate underuse of such medication by some marital status groups. METHODS: Using data from registers covering the entire Norwegian population, we analysed marital status differences in the purchase of medicine for eight circulatory disorders by people aged 50-79 in 2004-2008. These differences were compared with those in circulatory disease mortality during 2004-2007, considered as indicating probable differences in disease burden. RESULTS: The unmarried had 1.4-2.8 times higher mortality from the four types of circulatory diseases considered. However, the never-married in particular purchased less medicine for these diseases, or precursor risk factors of these diseases, primarily because of a low chance of making a first purchase. The picture was more mixed for the divorced and widowed. Both groups purchased less of some of these medicines than the married, but, especially in the case of the widowed, relatively more of other types of medicine. In contrast to the never-married, divorced and widowed people were as least as likely as the married to make a first purchase, but adherence rates thereafter, indicated by continuing purchases, were lower. CONCLUSION: The most plausible interpretation of the findings is that compared with married people, especially the never-married more often have circulatory disorders that are undiagnosed or for which they for other reasons underuse medication. Inadequate use of these potentially very efficient medicines in such a large population group is a serious public health challenge which needs further investigation. It is possible that marital status differences in use of medicines for circulatory disorders combined with an increasing importance of these medicines have contributed to the widening marital status gap in mortality observed in several countries. This also requires further investigation