The shape of invasion perclation clusters in random and correlated media

The shape of two-dimensional invasion percolation clusters are studied numerically for both non-trapping (NTIP) and trapping (TIP) invasion percolation processes. Two different anisotropy quantifiers, the anisotropy parameter and the asphericity are used for probing the degree of anisotropy of clusters. We observe that in spite of the difference in scaling properties of NTIP and TIP, there is no difference in the values of anisotropy quantifiers of these processes. Furthermore, we find that in completely random media, the invasion percolation clusters are on average slightly less isotropic than standard percolation clusters. Introducing isotropic long-range correlations into the media reduces the isotropy of the invasion percolation clusters. The effect is more pronounced for the case of persisting long-range correlations. The implication of boundary conditions on the shape of clusters is another subject of interest. Compared to the case of free boundary conditions, IP clusters of conventional rectangular geometry turn out to be more isotropic. Moreover, we see that in conventional rectangular geometry the NTIP clusters are more isotropic than TIP clusters

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

The reduction of intoxication and disorder in premises licensed to serve alcohol: An exploratory randomised controlled trial

Background: Licensed premises offer a valuable point of intervention to reduce alcohol-related harm. Objective: To describe the research design for an exploratory trial examining the feasibility and acceptability of a premises-level intervention designed to reduce severe intoxication and related disorder. The study also aims to assess the feasibility of a potential future large scale effectiveness trial and provide information on key trial design parameters including inclusion criteria, premises recruitment methods, strategies to implement the intervention and trial design, outcome measures, data collection methods and intra-cluster correlations. Design: A randomised controlled trial in licensed premises that had experienced at least one assault in the year preceding the intervention, documented in police or hospital Emergency Department (ED) records. Premises were recruited from four study areas by piloting four recruitment strategies of varying intensity. Thirty two licensed premises were grouped into matched pairs to reduce potential bias and randomly allocated to the control or intervention condition. The study included a nested process evaluation to provide information on intervention acceptability and implementation. Outcome measures included police-recorded violent incidents, assault-related attendances at each premises' local ED and patron Breath Alcohol Concentration assessed on exiting and entering study premises. Results: The most successful recruitment method involved local police licensing officers and yielded a 100% success rate. Police-records of violence provided the most appropriate source of data about disorder at the premises level. Conclusion: The methodology of an exploratory trial is presented and despite challenges presented by the study environment it is argued an exploratory trial is warranted. Initial investigations in recruitment methods suggest that study premises should be recruited with the assistance of police officers. Police data were of sufficient quality to identify disorder and street surveys are a feasible method for measuring intoxication at the individual level

Political Mediation and American Old-Age Security Exceptionalism

Debates over America’s heavy reliance on employer-provided private pensions have understated the profound role organized labor played after World War II. Archival evidence from prominent unions and business associations suggests that the shift in organized labor’s strategy after the New Deal toward electoral activity helps explain critical interventions by Northern Democrats into the system of private pensioning in the postwar period that laid the foundation for America’s old-age security system. Such a strategy was insufficient, however, to expand Social Security. This article offers a political mediation account of electoral activity as a source of labor influence on social policy that draws on political institutionalist and class power theories

The Amidase Domain of Lipoamidase Specifically Inactivates Lipoylated Proteins In Vivo

BACKGROUND:In the 1950s, Reed and coworkers discovered an enzyme activity in Streptococcus faecalis (Enterococcus faecalis) extracts that inactivated the Escherichia. coli and E. faecalis pyruvate dehydrogenase complexes through cleavage of the lipoamide bond. The enzyme that caused this lipoamidase activity remained unidentified until Jiang and Cronan discovered the gene encoding lipoamidase (Lpa) through the screening of an expression library. Subsequent cloning and characterization of the recombinant enzyme revealed that lipoamidase is an 80 kDa protein composed of an amidase domain containing a classic Ser-Ser-Lys catalytic triad and a carboxy-terminal domain of unknown function. Here, we show that the amidase domain can be used as an in vivo probe which specifically inactivates lipoylated enzymes. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated whether Lpa could function as an inducible probe of alpha-ketoacid dehydrogenase inactivation using E. coli as a model system. Lpa expression resulted in cleavage of lipoic acid from the three lipoylated proteins expressed in E. coli, but did not result in cleavage of biotin from the sole biotinylated protein, the biotin carboxyl carrier protein. When expressed in lipoylation deficient E. coli, Lpa is not toxic, indicating that Lpa does not interfere with any other critical metabolic pathways. When truncated to the amidase domain, Lpa retained lipoamidase activity without acquiring biotinidase activity, indicating that the carboxy-terminal domain is not essential for substrate recognition or function. Substitution of any of the three catalytic triad amino acids with alanine produced inactive Lpa proteins. CONCLUSIONS/SIGNIFICANCE:The enzyme lipoamidase is active against a broad range of lipoylated proteins in vivo, but does not affect the growth of lipoylation deficient E. coli. Lpa can be truncated to 60% of its original size with only a partial loss of activity, resulting in a smaller probe that can be used to study the effects of alpha-ketoacid dehydrogenase inactivation in vivo

Cross-sectional measures and modelled estimates of blood alcohol levels in UK nightlife and their relationships with drinking behaviours and observed signs of inebriation

<p>Abstract</p> <p>Background</p> <p>Management of nightlife in UK cities focuses on creating safe places for individuals to drink. Little is known about intoxication levels as measuring total alcohol consumption on nights out is complicated by early evening interviews missing subsequent consumption and later interviews risking individuals being too drunk to recall consumption or participate at all. Here we assess mixed survey and modelling techniques as a methodological approach to examining these issues.</p> <p>Methods</p> <p>Interviews with a cross sectional sample of nightlife patrons (n = 214) recruited at different locations in three cities established alcohol consumption patterns up to the point of interview, self-assessed drunkenness and intended drinking patterns throughout the remaining night out. Researchers observed individuals' behaviours to independently assess drunkenness. Breath alcohol tests and general linear modelling were used to model blood alcohol levels at participants' expected time of leaving nightlife settings.</p> <p>Results</p> <p>At interview 49.53% of individuals regarded themselves as drunk and 79.43% intended to consume more alcohol before returning home, with around one in ten individuals (15.38% males; 4.35% females) intending to consume >40 units (equal to 400 mls of pure alcohol). Self-assessed drunkenness, researcher observed measures of sobriety and blood alcohol levels all correlated well. Modelled estimates for blood alcohol at time of going home suggested that 71.68% of males would be over 0.15%BAC (gms alcohol/100 mls blood). Higher blood alcohol levels were related to drinking later into the night.</p> <p>Conclusions</p> <p>UK nightlife has used substantive health and judicial resources with the aim of creating safer and later drinking environments. Survey and modelling techniques together can help characterise the condition of drinkers when using and leaving these settings. Here such methods identified patrons as routinely getting drunk, with risks of drunkenness increasing over later nights. Without preventing drunkenness and sales to intoxicated individuals, extended drinking hours can simply act as havens for drunks. A public health approach to nightlife is needed to better understand and take into account the chronic effects of drunkenness, the damages arising after drunk individuals leave city centres and the costs of people avoiding drunken city centres at night.</p

Cholera Toxin B Subunits Assemble into Pentamers - Proposition of a Fly-Casting Mechanism

The cholera toxin B pentamer (CtxB5), which belongs to the AB5 toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB5 and the related heat labile enterotoxin LTB5 have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them