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The expression of most Staphylococcus aureus virulence factors is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (AIP). A polymorphism in the amino acid sequence of the AIP and of its corresponding receptor divides S. aureus strains into four major groups. Within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the AIPs belonging to different groups are usually mutually inhibitory. We investigated a possible relationship between agr groups and human S. aureus disease by studying 198 S. aureus strains isolated from 14 asymptomatic carriers, 66 patients with suppurative infection, and 114 patients with acute toxemia. The agr group and the distribution of 24 toxin genes were analyzed by PCR, and the genetic background was determined by means of amplified fragment length polymorphism (AFLP) analysis. The isolates were relatively evenly distributed among the four agrgroups, with 61 strains belonging to agr group I, 49 belonging to group II, 43 belonging to group III, and 45 belonging to group IV. Principal coordinate analysis performed on the AFLP distance matrix divided the 198 strains into three main phylogenetic groups, AF1 corresponding to strains of agr group IV, AF2 corresponding to strains of agr groups I and II, and AF3 corresponding to strains of agr group III. This indicated that the agr type was linked to the genetic background. A relationship between genetic background, agr group, and disease type was observed for several toxin-mediated diseases: for instance, agr group IV strains were associated with generalized exfoliative syndromes, and phylogenetic group AF1 strains with bullous impetigo. Among the suppurative infections, endocarditis strains mainly belonged to phylogenetic group AF2 and agr groups I and II. While these results do not show a direct role of the agr type in the type of human disease caused by S. aureus, the agr group may reflect an ancient evolutionary division of S. aureus in terms of this species' fundamental biology.
Staphylococcus aureus is both a commensal and an extremely versatile pathogen in humans, causing three basic syndromes: (i) superficial lesions such as skin abscesses and wound infections; (ii) deep-seated and systemic infections such as osteomyelitis, endocarditis, pneumonia, and bacteremia; and (iii) toxemic syndromes such as toxic shock syndrome (TSS) and staphylococcal scarlet fever (both due to toxic shock syndrome toxin 1 [TSST-1] and staphylococcal enterotoxins [SEs]), staphylococcal scalded-skin syndrome (SSSS; due to exfoliatins), and staphylococcal food poisoning (due to SEs) (1, 18, 24). With the exception of toxemia, the molecular basis of S. aureus pathogenicity is multifactorial, depending on the expression of a large class of accessory gene products that comprise cell wall-associated and extracellular proteins (24). Expression of most virulence factors in S. aureus is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is a bacterial-density-sensing peptide (autoinducing peptide) also encoded by agr (24). A polymorphism in the amino acid sequence of the autoinducing peptide and of its corresponding receptor (AgrC) has been described. S. aureus strains can be divided into four major groups on this basis: within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the autoinducing peptides produced by the different groups are usually mutually inhibitory (14, 16). Links between a peculiar agr type and a specific staphylococcal syndrome have been shown for TSS and SSSS. TSST-1-producing isolates belong to agr specificity group III (16) and mostly belong to a single clone, as shown by multilocus enzyme electrophoresis (MLEE) (23) and pulsed-field gel electrophoresis (PFGE) (3). Most exfoliatin-producing strains responsible for SSSS belong to agr group IV, but the clonality of these strains has not been investigated (14). agr group I was prevalent in a collection of 192 S. aureus strains, most of which were methicillin resistant, but no clinical information was available in this study (29).
The aim of the present study was to further investigate a possible relationship between agr groups (alleles) and the pattern of S. aureus disease. We studied 198 methicillin-susceptible strains from the French National Reference Center for Staphylococcal Toxemia strain collection, in which all clinical syndromes are represented, to determine their agr type and the distribution of 24 toxin genes (by PCR), as well as to determine their genetic background (by amplified fragment length polymorphism [AFLP] analysis). We then sought to determine the relationships between these characteristics and the type of clinical disease syndrome.
Staphylococcal strains and corresponding disease syndromes.The French National Reference Center for Staphylococcal Toxemia (Lyon, France) collects more than 800 strains yearly from patients with toxemic and nontoxemic staphylococcal diseases throughout France. For this study we selected a subset of 198 S. aureus strains isolated between January 1985 and December 1999. They were isolated from nose swabs (n = 3) and vaginal swabs (n = 11) of 14 asymptomatic carriers and from clinical specimens of 66 patients with S. aureus suppurative infections (necrotizing pneumonia caused by Panton-Valentine leukocidin-producing strains [n = 11], furunculosis [n = 11], native valve endocarditis [n = 19], finger pulp infections [n = 9], osteitis [n = 8], cellulitis and/or myositis [n = 4], and arthritis [n = 4]), 4 patients with enterocolitis, and 114 patients with acute toxemia, including 35 cases of TSS, 33 cases of staphylococcal scarlet fever, and 46 cases of SSSS (20 cases of generalized exfoliative syndrome and 26 cases of bullous impetigo). The types of infection were defined according to published criteria (8, 18, 19). All infections were community acquired. All of the strains were collected from hospitals located throughout France and were identified as S. aureus by their ability to coagulate citrated rabbit plasma (bioMérieux, Marcy l'Etoile, France) and to produce a clumping factor (Staphyslide Test; bioMérieux).
S. aureus strains RN6390 (agr group I), RN6923 (agr group II), RN8462 (agr group III), A980740 (agr group IV), and RN6911 (agr null) were used as controls for agr group identification (14, 16). Control strains used for toxin gene detection are listed in Table 1.
Culture and DNA extraction.Strains were grown on brain heart infusion agar or in the same broth at 37°C overnight. Genomic DNA used as target for PCR and AFLP assays was extracted by using a standard phenol-chloroform procedure (26), and the concentration of DNA was estimated spectrophotometrically (26).
Identification of agr alleles.The primers Pan-1 (5′-ATG CAC ATG GTG CAC ATG CA-3′) and Pan-2 (5′-CAT AAT CAT GAC GGA ACT TGC TGC GCA-3′) (Eurogentec, Seraing, Belgium) were designed from agr group I to IV sequences (GenBank accession numbers M21854 , AF001782 , AF001783 , and AF288215 , respectively) to amplify a 1,234-bp agr fragment encompassing the 3′ end of agrB, all of agrD, and the 5′ end of agrC. Amplification was carried out on a PE-9600 thermocycler (Perkin-Elmer Corp., Norwalk, Conn.) under the following conditions: an initial 5-min denaturation step at 95°C; followed by 30 cycles of 1 min of denaturation at 94°C, 1 min of annealing at 55°C, and 1 min of extension at 72°C; and a final extension step at 72°C for 10 min. The PCR products were purified by using the High Pure kit (Boehringer Mannheim) and sequenced with the primers used for PCR (Genome Express, Grenoble, France). The 198 strains were assigned to one of the four agr groups by comparing the predicted product of AgrD and the N-terminal half of AgrC with those of the four control strains (see above).
Toxin gene detection.Sequences specific for sea-e, seg-j, sem-o, tst, eta, etb, lukS-PV-lukF-PV, lukE-lukD, lukM, hla, hlb, hld, hlg, hlg-2, and edin, encoding SEA-E; SEG-J; SEM-O; TSST-1; ETA; ETB; PVL components S and F; LUKE-LUKD; LUKM; the alpha-, beta-, delta-, gamma-, and gamma variant hemolysins; and EDIN, respectively, were detected by PCR on a PE-9600 thermocycler (Perkin-Elmer ) as previously described (15, 19) with the primers shown in Table 1 (Eurogentec). Amplification of gyrA was used to confirm the quality of each DNA extract and the absence of PCR inhibitors (5). All PCR products were analyzed by electrophoresis through 1% agarose gels (Sigma, Saint Quentin Fallavier, France). The distribution of the 24 toxin genes among the 198 strains is available on-line (ftp://pbil.univ-lyon1.fr/pub/datasets/statox.txt ).
AFLP.The Perkin-Elmer AFLP Microbial Fingerprinting Kit was used according to the manufacturer's recommendations, except that the TaqI primers and adapter were as described by Vos et al. (30). The following two AFLP conditions were used, with one selective nucleotide added at the 3′ extremity of each primer: EcoRI + A/TaqI + C (condition A/C) and EcoRI + T/TaqI + G (condition T/G). Touchdown PCR cycling was done as recommended by the manufacturer, in a PE-9600 thermocycler (Perkin-Elmer). Processed DNA samples were loaded in pools of two with fluorescent dyes in 6% (wt/vol) denaturing polyacrylamide gels for electrophoresis (ABI Prism 373 Sequencer; Perkin-Elmer).
AFLP data processing.Perkin-Elmer GeneScan analysis software was used to extract data from electropherograms. Assignation of fragments to discrete categories, transformation of data into tabular binary matrices (LecPCR program), and calculation of genomic distance (DistAFLP program), with or without bootstrap resamplings, were done as previously described (22). The LecPCR and DistAFLP programs are freely available on the ADE-4 web server (http://pbil.univ-lyon1.fr/ADE-4/microb ). DistAFLP provides output files in the ADE-4 binary format suitable for multivariate analysis (28). Genomic distances are estimated rates of nucleotide substitution over whole genomes by using the Dice similarity index and Jukes-Cantor correction (22).
Statistical analysis.The table of toxin gene detection in the 198 isolates was analyzed by using classical principal component analysis (PCA). Only 19 toxin genes were used, since four were either always present (hla and hld) or always absent (edin and lukM). The AFLP results (distance matrix between the 198 strains) were analyzed by using principal coordinate analysis (PCO) (11). This method provides a description of the main structures of distance matrices in the form of factor maps, in the same way as PCA. PCA of the toxin genes and PCO of the AFLP results gave independent results, and the corresponding graphics cannot be compared. However, these two analyses can be linked by co-inertia analysis (CIA) (7), so that the results can be compared and the factor maps can be superimposed. CIA gives co-inertia axes that have the maximum possible covariance with the variables in each of the two data sets. By using the covariance instead of the correlation (as in canonical correlation analysis), CIA maximizes the product of the correlation by the projected variances, ensuring that co-inertia axes will have both a good correlation with the initial variables and real meaning for each of the two data sets (7).
Phylogenetic distribution of the clinical S. aureus strains.Since any relationship between the agr group and disease type would have to be interpreted according to the strain's genetic background, we first conducted AFLP analysis of the 198 strains. PCO was performed on the distance matrix of the 198 isolates obtained by using the AFLP results to calculate genome divergence (i.e., the rate of nucleotide substitutions over whole genomes) between pairs of isolates. Figure 1 shows the factor map of the AFLP PCO. Since the first axis, F1, accounted for 22% of the variance, and the second axis, F2 (orthogonal to F1), accounted for the largest part (14%) of the variance not accounted for by F1 (data not shown), the results are expressed as the projections of each strain on a plane defined by these two axes, which were conserved for further analysis. This analysis divided the strains into three main phylogenetic groups, namely, AF1, a group with positive values on the F2 axis; AF2, a group with negative values on both the F1 and F2 axes; and AF3, a group distinguished from AF1 by negative values on the F2 axis.
To evaluate the possible relationship between the disease type and the bacterial genetic background, the same AFLP PCO factor map was split according to the different diseases (classified in 13 disease types designated A to M, Table 2) for a better understanding of this relationship (Fig. 2). This analysis shows that the strains involved in scalded skin syndrome (disease type A) and bullous impetigo (disease type B) mainly belonged to phylogenetic group AF1 (27 of 46 strains). Enterotoxin-producing strains associated with scarlet fever and TSS (disease type C) mainly belonged to phylogenetic group AF2 (35 of 40 strains). The strains involved in TSST-1-associated disease (scarlet fever and menstrual and nonmenstrual TSS) (disease type D) belonged principally to phylogenetic group AF3 (21 of 28 strains). In contrast to toxin-mediated diseases, strains associated with suppurative infections (group E to M) did not seem to be specifically related to a particular AFLP cluster. Only endocarditis strains (disease type E) were mainly related to phylogenetic group AF2 (16 of 19 strains). The strains associated with diseases I, J, K, and L rarely belonged to group AF1. Interestingly, the strains associated with necrotizing pneumonia (disease F) and furuncles (disease H), which are both caused by Panton-Valentine leukocidin-producing strains (19), belonged to three phylogenetic groups, and the two graphics were highly superimposable.
Relationships between agr groups, genetic background, and disease type.The agr group of the 198 S. aureus isolates was analyzed by amplification and sequencing. All isolates were classified as part of one of the four agr groups, and the distribution was relatively even, with 61 strains belonging to agr I, 49 belonging to agr II, 43 belonging to agr III, and 45 belonging to agr IV (Table 2). The AFLP PCO factor map for the 198 isolates was then split according to the four agr groups (Fig. 3). This clearly individualized strains from groups III and IV, while strains from groups I and II were partly superimposed. Thus, there was a very strong relationship between the AFLP cluster and the agr group in spite of the fact that a few isolates appeared to be outliers from the clusters of isolates belonging to the same agr group (four strains of agr group I, four strains of agr group II, six strains of agr group III, and three strains of agr group IV). This finding clearly indicated that agr types are associated with genetic backgrounds of strains. agr group labeling of each isolate on the AFLP PCO factor map showed a clear relationship between the genetic background, the agr group and the disease type, particularly for toxin-mediated diseases (Fig. 2, panels A to D). For instance, agr group IV strains involved in generalized exfoliative syndrome and bullous impetigo (disease groups A and B) were particularly associated with phylogenetic group AF1. Likewise, agr group III strains involved in TSST-1-mediated diseases (disease group D) were particularly associated with phylogenetic group AF3, and strains causing SE-mediated diseases (disease group C) belonged to agr group I or II and phylogenetic group AF2.
Relationships between toxin genes and genetic background.To determine whether the observed link between toxin-mediated diseases and genetic background was also found at the level of toxin genes, we analyzed the relationship between the distribution of 24 toxin genes and the genetic background. We first determined whether preferential combinations of toxin genes occurred among the 198 clinical strains, by means of PCA. Since the first axis, F1, and the second axis, F2 (orthogonal to F1), accounted for the largest part of the variance in PCA (40 and 21%, respectively), the results were expressed as the projections of each toxin gene on a plane defined by these two components (F1 and F2) (Fig. 4). On the first component, a group of five toxin genes (seg, sei, sen, seo, and sem, all encoded by the enterotoxin gene cluster) (15) was clearly individualized and slightly opposed to sea. On the second component there was an opposition between hlg-2 (together with lukE-lukD and, less strongly, eta and etb) and hlg (and, to a lesser extent, tst and seh). The other toxin genes (seb, sec, sed, sej, hlb, and lukS-PV-lukF-PV) were too near to the origin to be interpreted. The preferential combinations or exclusions of toxin genes suggested a nonrandom distribution of toxin genes in these strains.
To confirm the link between the toxin gene distribution and the genetic background of the strains, we coupled the AFLP clusters and the toxin gene analysis by using CIA (7). The PCA of the toxin gene table and the PCO of the AFLP results were coupled. Figure 5 shows the CIA factor map for the toxin genes, while Fig. 6 shows the CIA factor map for the AFLP patterns of the 198 isolates. These factor maps were very similar to the factor maps of the separate analyses (Fig. 3 and 4). The correlation coefficients between the co-inertia axes were 0.813 and 0.783 for the first and second axes, respectively. The percentages of variance derived from the co-inertia axes were 92 and 86% for the first axis in the toxin gene space and in the AFLP space, respectively. For the first two axes, the corresponding percentages were 98 and 83%. These very strong correlations and percentages of explained variance reflected a strong relationship between the toxin gene distribution and AFLP clusters. Hence, tst and hlg were associated with phylogenetic group AF3 and opposed to groups AF1 and AF2. The five genes belonging to the enterotoxin gene cluster (seg, sei, sem, sen, and seo) were associated with group AF1 and opposed to group AF2. lukD-lukE and hlg-2 were opposed to phylogenetic group AF3 and associated with groups AF1 and AF2. eta and etb were associated with phylogenetic group AF1 (Fig. 5 and 6). The distribution of the 24 toxin genes, the agr group, and the AFLP group among the 198 strains is available on-line (ftp://pbil.univ-lyon1.fr/pub/datasets/statox.txt ).
We investigated a possible relationship between agr groups and the pattern of S. aureus disease and found a strong association between the agr types and certain diseases. However, in most cases the association reflected the link between the disease types, the pattern of toxin genes, and the genetic background of the strains. For instance, the strains causing SE-mediated diseases (disease group C) belonged to agr group I or II and phylogenetic group AF2. We thus concluded that, in most of the disease types considered (mainly toxin-mediated diseases), the agr alleles and toxin genes evolved contemporaneously with their parent strains and that horizontal transfer played only a marginal role. These findings confirm that specific bacterial pathogenicities are each essentially associated with a specific clone or group of clones.
The association of virulence factors with specific backgrounds has been discussed recently for several bacterial species such as Escherichia coli, in which a clonal distribution of virulence genes has been reported among clinical strains isolated from bloodstream infections (12, 20), neonatal meningitis (2), and extraintestinal infections (25). Regarding S. aureus, multilocus sequence typing comparison of isolates recovered from asymptomatic nasal carriers and from patients with severe diseases revealed that invasive diseases were primarily caused by a subset of genotypes unrepresentative of the carriage population as a whole (4). Another study of the genetic structure of S. aureus, involving MLEE, revealed that a single clone (designated ET41) of S. aureus producing TSST-1 causes most epidemiologically unrelated cases of urogenital TSS (23). The observation of a large proportion of asymptomatic female genital-tract carriers of this clone suggested that ET41 was highly adapted to the cervicovaginal tract. More recently, Booth et al. (3) used PFGE to analyze 405 clinical isolates of S. aureus and found that five phylogenetic lineages were highly prevalent and widely distributed, in contrast to 85 other lineages which occurred with frequencies of <2.5%. One of the five prevalent lineages (SAL1) comprised most TSST-1-producing strains, confirming the observation by Musser et al. (23). Booth et al. also found that SAL1 was enriched among the normal flora of the anterior nares and that lineage SAL4, which comprised 90% of methicillin-resistant S. aureus (MRSA) strains, was significantly associated with respiratory tract infections (3).
We studied a different population of methicillin-susceptible S. aureus clinical strains causing a broad spectrum of community-acquired infections. In agreement with the findings of Musser et al. (23) and Booth et al. (3), we confirmed the clonality of TSST-1-producing strains. In addition, we found that a number of diseases, such as SSSS, bullous impetigo, scarlet fever, TSS and, to a lesser extent, infective endocarditis, were preferentially associated with one of the three phylogenetic lineages that structured our strain population. In this respect, we fully agree with the concept developed by Falkow et al. that "the basic unit of bacterial pathogenicity is the clone or lineage that expands due to the possession of unique combinations of virulence genes" (10). With the exception of infective endocarditis, most of the diseases listed above are caused by specific toxins whose genetic determinants are frequently carried by potentially mobile elements such as plasmids (etb, seb, etc.), phages, or pathogenicity islands (tst, egc, lukFD-lukSE, etc.) (17). CIA, used to couple PCA of the toxin gene table (Fig. 4) and PCO of the AFLP results (Fig. 1), clearly indicated that the distribution of toxin genes was closely linked to the strain's genetic background (Fig. 5 and 6). This suggested that the virulence determinants did not spread homogeneously among various genetic backgrounds or, at least, that the efficiency of such genetic exchanges between the three major lineages was low. Similarly, Booth et al. found that tst, cna (the collagen-binding protein gene), and hlb were associated with certain PFGE lineages and not with others, suggesting limited horizontal transfer among lineages (3). This is in accordance with the observation that, in E. coli, horizontal transfer generally does not disrupt the clonal structure of the species (6, 21, 27). A stable link between virulence and phylogeny could correspond to the necessity of having virulence determinants move into a particular genetic background for the emergence of a "virulent clone" (9, 10, 25). In contrast, PVL-associated diseases (necrotizing pneumonia and furunculosis) appeared to be caused by strains of the three lineages (Fig. 2). Since PVL is encoded by a bacteriophage, it is likely that in this case the bacteriophage has spread easily among the different backgrounds. With other suppurative diseases (groups I, J, K, and L [i.e., osteitis, finger pulp infections, arthritis, and enterocolitis, respectively]), the rarity of associations with phylogenetic group AF1 (Fig. 2) cannot yet be interpreted, since we do not know the virulence factors specifically involved in these infections. Microbial surface component-recognizing adhesive matrix molecules are likely play a role in these settings (13).
Considering the possible relation between the agr group and the disease type, we first postulated a relation between the agr group and the capacity to induce a specific disease. Ji et al. observed that the vast majority of menstrual toxic shock strains belonged to agr group III but that strains belonging to the other two groups had no apparent clinical specificity (16). We have previously shown that most ET-producing strains belong to agr group IV (14). In another study, agr group I was the most prevalent among 192 carrier and disease isolates, but 71% of the isolates were MRSA strains, which are known to be highly clonal (29). In our carefully selected collection of S. aureus clinical isolates (mainly causing community-acquired infections), the four agr types were relatively evenly distributed (Table 2). The agr group distribution correlated strongly with the genetic background of the strains and thus, indirectly, with certain disease profiles. The observed link between the agr group and genetic background was also found among coagulase-negative staphylococci in our laboratory: amplification-sequencing yielded 25 distinct agr variants among 13 staphylococcal species; the overall topology of the phylogenetic tree constructed from the DNA sequences of the 25 agr alleles was remarkably similar to that constructed from 16S rRNA loci of the 13 staphylococcal species, arguing against significant horizontal transfer of agr genes between populations of staphylococci (D. Dufour et al., unpublished data). As proposed by Novick, this agr grouping may represent the first subdivision of S. aureus based on the fundamental biology of the organism (24). Finally, though we cannot attribute a direct responsibility of the agr type in disease initiation, we can speculate that the preferential association between certain agr alleles, certain toxin genes, and a particular genetic background may make the activation of virulence factors more efficient. To paraphrase Falkow (10), we propose that the basic unit of bacterial pathogenicity would be the clone or lineage, which expands because it possesses particular combinations of virulence and regulatory genes in the appropriate genetic background.
We thank N. Violland, C. Courtier, and C. Gardon for technical assistance and D. Young for editing the manuscript.
This work was made possible by using the sequencing device facilities of the DTAMB at UCBL.
- Received 18 June 2001.
- Returned for modification 2 October 2001.
- Accepted 1 November 2001.
- Copyright © 2002 American Society for Microbiology


text: Advice Finding the right school for your vision impaired child Choosing a school is a big decision for you and your child. To help you feel confident in making this decision, here are some tips. Find out more Different school options explained Some things to consider when choosing your school Find out more Dealing with a vision impairment diagnosis There are several signs to look out for if you think your child may have a visual impairment. Follow these steps towards a diagnosis and hear stories from parents and young people who have been through it. Find out more Starting playgroup or nursery Most vision impaired children are able to go to a mainstream playgroup or nursery. Find out more Helping your child to develop and learn Practical advice and suggestions to help your vision impaired baby or toddler develop and learn. Find out more Recruiting people with vision impairment By law your recruitment policy must be inclusive, a disabled job applicant must not be disadvantaged within the recruitment process. Find out more Treating disabled employees fairly A vision impairment, or any other disability, should not stand in the way of work. Equality laws protect disabled people to make sure that they aren't at a disadvantage at work. This applies when they're applying for or doing a job. Find out more Things you can do to help your vision impaired baby's development How you can help your vision impaired baby learn and explore the world around them. Find out more Eye care professionals Understand the roles of different eye care professionals. Here we explain the roles of Orthoptists, Optomestrists, Opticians and Ophthalmologists. Find out more Pagination First page « First Previous page ‹‹ Page 1 Current page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Next page ›› Last page Last »

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About Dædalus
Representing the intellectual community in its breadth and diversity, Dædalus explores the frontiers of knowledge and issues of public importance.
Dædalus was founded in 1955 and established as a quarterly in 1958. The journal's namesake was renowned in ancient Greece as an inventor, scientist, and unriddler of riddles. Its emblem, a maze seen from above, symbolizes the aspiration of its founders to "lift each of us above his cell in the labyrinth of learning in order that he may see the entire structure as if from above, where each separate part loses its comfortable separateness."
Drawing on the enormous intellectual capacity of the American Academy of Arts and Sciences, whose members are among the world's most prominent thinkers in the sciences, humanities, arts, and social sciences, as well as the professions and public life, each issue of Dædalus features multidisciplinary, authoritative essays centered on a theme or subject.
Dædalus continues the volume and numbering system of Proceedings of the American Academy of Arts and Sciences, which ceased publication under that title with volume 85 in 1958.
Subscriptions to Dædalus are available through MIT Press Journals. Past issues of Dædalus are available through JSTOR and The MIT Press. For more information on accessing the journal, please click here.
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A hit-and-run accident involving a Corvette in the early morning of February 6, 2012 left a South Florida man happy he's still alive.
Joe Amunategui told authorities he was headed eastbound on 826 just past Northwest 27th Avenue about 2 a.m. when a tractor-trailer clipped his C5 Corvette and drove over it, then kept going.
"He came up real close and as he was swerving to go around me, he clipped the back of my Corvette and spun me into the wall," Amunategui said. "I'm lucky to be alive right now … I took a pretty good shot."
The front end of his Corvette has definitely seen better days. In a photo posted on the web site of NBC Channel 6 in Miami, the hood appears to be gone, one headlight is popped up, and the passenger-side front fender is snapped in half near the front of the tire and mangled behind the tire, not to mention the entire front bumper is scraped and dented. Things could be much worse, though. From the windshield back, the car looks to have escaped serious damage, and the car appears to be a convertible, so Amunategui is really fortunate that the big rig didn't drive over the canvas top.
A North Miami Beach officer saw what happened and radioed for assistance, but police are still investigating the incident.
As for Amunategui, he says he felt a little dizzy and would probably get some X-rays.
"It's not the way I wanted to end my night," he said.
NBC Channel 6
Drunk Driver Crashes Into New Corvettes at a Miami Chevy Dealership
Woman Speeds out of Ferrari Dealership and Crashes Corvette
[ACCIDENTS] 1978 Corvette Pace Car vs Semi Truck


text: Home / Add-on to Kits or Book for Kids / Story Problems the Fun Way Story Problems the Fun Way$18.95 Story Problems the Fun Way quantity Add to cart SKU: SPT Categories: Add-on to Kits or Book for Kids, Shippable Products Description Additional information Reviews (0) Description Students are eager to solve these colorfully illustrated mind puzzles. There are several levels of difficulty which include one and two step solutions to everyday problems. Students will practice applying the basic math facts including addition, subtraction, multiplication, and division. Teachers are able to assign sections that focus on specific skills. Item ID: SPT Related Additional information Weight 0.85 lbs Reviews There are no reviews yet. Be the first to review "Story Problems the Fun Way" Cancel replyYour rating * Rate… Perfect Good Average Not that bad Very poor Your review *Name * Email * Related products Times Tables the Fun Way Clue Cards0 out of 5 $10.95 Add to cart Sale! Times and Division Teacher Kit 4010 out of 5 $122.60 $93.95 Add to cart Times Tables the Fun Way Teacher's Manual0 out of 5 $24.95 Add to cart Times Alive Software0 out of 5 $58.95 Add to cart


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Most experiments show that one neural correlate of attention is enhanced firing. If a neuron has a certain response to a stimulus when the animal is not attending to the stimulus, then when the animal does attend to the stimulus, the neuron's response will be enhanced even if the physical characteristics of the stimulus remain the same.
In a recent review, Knudsen[9] describes a more general model which identifies four core processes of attention, with working memory at the center:
- Working memory temporarily stores information for detailed analysis.
- Competitive selection is the process that determines which information gains access to working memory.
- Through top-down sensitivity control, higher cognitive processes can regulate signal intensity in information channels that compete for access to working memory, and thus give them an advantage in the process of competitive selection. Through top-down sensitivity control, the momentary content of working memory can influence the selection of new information, and thus mediate voluntary control of attention in a recurrent loop.
- Bottom-up saliency filters automatically enhance the response to infrequent stimuli, or stimuli of instinctive or learned biological relevance.
Neurally, at different hierarchical levels spatial maps can enhance or inhibit activity in sensory areas, and induce orienting behaviors like eye movement.
- At the top of the hierarchy, the frontal eye fields (FEF) on the dorsolateral frontal cortex contain a retinocentric spacial map. Microstimulation in the FEF induces monkeys to make a saccade to the relevant location. Stimulation at levels too low to induce a saccade will nonetheless enhance cortical responses to stimuli located in the relevant area.
- At the next lower level, a variety of spacial maps are found in the parietal cortex. In particular, the lateral intraparietal area (LIP) contains a saliency map and is interconnected both with the FEF and with sensory areas.
- Certain automatic responses that influence attention, like orienting to a highly salient stimulus, are mediated subcortically by the superior colliculi.
- At the neural network level, it is thought that processes like lateral inhibition mediate the process of competitive selection.


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Hey - just in case any locals haven't received the telex, up-and-coming Hamburg freak duo Schluss are performing at the Oberdeck tonight. Our very own Paranoid Leather will be stretched out in the DJ lounger as well. Komm!
TLASILA Blog: A forum for all things related (and of interest) to the experimental collective To Live and Shave in L.A. Founded by Tom Smith in May 1990, TLASILA is antithesis, energized at the juncture of aesthetic revulsion. Genre is obsolete.
Thursday, March 29, 2018
Monday, March 26, 2018
Convalescence: Day Eighteen
Hi again,
Well, I returned to work today, but first I had my stitches removed!
The nurse who did the honors commented on the relatively rapid healing processes that seem to be underway, but I won't be happy until I can chuck the crutches and get back to competitive power loitering. Rehearsing later with Bianca and Andreas at the Merkwürdig Riechnerv bunker.
(I realize the affected area looks particularly unsavory. It's been under wraps since the accident on February 28th...)
Well, I returned to work today, but first I had my stitches removed!
The nurse who did the honors commented on the relatively rapid healing processes that seem to be underway, but I won't be happy until I can chuck the crutches and get back to competitive power loitering. Rehearsing later with Bianca and Andreas at the Merkwürdig Riechnerv bunker.
(I realize the affected area looks particularly unsavory. It's been under wraps since the accident on February 28th...)
Sunday, March 25, 2018
Convalescence: Day Seventeen / Salt
Carol Levy's cover design for the Boat Of album that never made it to fruition. She decided it should be named Salt, and so it would have been. The label that had been sniffing around weren't serious, and it's probably all for the better. We were too fucking too much for 1981. Carol's illustration has yellowed with age but the late Ms. Levy remains 100% acetylene.
Saturday, March 24, 2018
New on Karl Schmidt Verlag
Available now on Karl Schmidt Verlag and Adult Contemporary Recordings: Cup of Indignation by Boat Of, a 60-minute generative chronology (i.e., an assemblage of stochastically distributed, non-static loops) covering a wide swath of the group's recorded output from 1979 to 1984. Yowza! With the Boat Of compilation cassette Forbidden Mourning Practice forthcoming on Hitomi Arimoto's unhinged 777 Was 666 imprint, it's a very good time to be against every fucking thing that exists all over again.
No physical edition at present. My broken leg precludes hauling parcels into the post for at least another month. Lossless digital, €7.99 at KSV Bandcamp.
Boat Of is quite the complicated beast. Our original idea was to change the name of the group with each live performance and / or shift in direction, but of course the conceit quickly revealed its limitations as soon as we began to be asked to play venues a second time!
I started alone as Prepared Party (in the Cage-ian sense) in 1979, mainly using a shortwave receiver and tape edits. With bassist Mike Green, guitarist Carol Levy, and occasional organist Mike Stipe (we never called him "Michael"), we morphed into Pre-Cave. I made the tape edits, played drums or discarded parts of drum kits, and worked with radios, turntables, and my Farfisa. Sometimes synths too. Sometimes with clothes dryers filled with shoes to create more stochastic rhythms! We rehearsed in an earthen basement at the Cobb Institute in Athens, GA, and furtively in the Method Actors' upstairs space when they were away on tour. The "pre" was also a reference to PRE, the aesthetic strategy I first promulgated in ish #1 of Hot Java, a short-lived arts newspaper published in Athens in 1980.
We had a show booked at the 40 Watt Club in Athens for June 26, 1980, but for some forgotten reason it fell through. Afterwards, we again changed the name of the group to Nest (adj.). (As in, "nest" as an adjective. Mike Green and I were disgustingly deep into semiotics, textual manipulation, etc., but also inveterate wags deeply cynical about the nascent Athens music scene. Dark humor and obscure puns were characteristic elements of our interactions, and remain so to this day. Boat Of Say 'Put'!)
Nest (adj.) had its first gig at the 40 Watt in October of 1980. MSG couldn't make it, but Carol, Stipe, my then-girlfriend Mary and I showed up with osmium chips on our shoulders. It was quite a good performance and a decent turnout. Maybe 85 people? It seemed phenomenal at the time. There was a second Nest (adj.) show on Valentine's Day, 1981. Afterwards we took a break while Mary and I made a mess of wedlock and unsuccessfully pretended to be normal. I was recording constantly, refining the edits and inching closer to the sound I'd always heard in my head, a Stygian readymade melange informed as much by the stylistic motifs of my favorite Enjoy and Sugarhill 12" singles as Xenakis or Lee Perry - our range of influences fell noticeably outside those of our peers.
When the group returned in May, we had adopted the name Boat Of, and we remained so limned through late March 1983, when Carol was killed in a dreadful car crash.
So, attributing all the recordings on Cup of Indignation to Boat Of is a form of shorthand. I never tire of relating the tale, but I suppose it might be a bit taxing for those who aren't so interested in convoluted origin sagas.
Boat Of's personnel shifted slightly from Pre-Cave/Nest (adj.) - Stipe played the June 1981 gig with us, but afterwards focused his energies on M.R.E. He invited me to one of their early gigs... I was horrified by their dire farmer-rock, and our friendship ended.
David Gamble, one half of the exemplary Method Actors, quit that group in the summer of 1981 to join ours on drums and vocals. Sandra-Lee Phipps, a lovely friend of Carol's with a refined wit and great stage presence, cast her lot with ours on vocals. My high school pal Don Fleming also contributed (taped drum machine and library recordings) to the burgeoning collective.
We were obsessed with "field hollers" and glossolalia. David covered the latter, and Sandi the former.
Jim Walker, a friend of mine from the outback and a huge Pip Pyle / Hatfield and the North / National Health fan, sometimes joined us on drums as well. Because PiL's original (Canadian) drummer had the same name, and since the American television actor Jimmy "Dyn-o-mite" Walker was - at least through the mid-1980s - such a recognized star, we never knew what to call our Jim. Usually we wrote something like "not the guy from Public Image and The Pack, but a really cool drummer nonetheless!"
Dominique Amet and Davey Stevenson from the excellent Limbo District (the only Athenian band with whom we really felt kinship) also joined, performing and recording radio sessions with us from late summer '82 through the winter of 1983. Dominique fell into our orbit earlier, actually - she appears on a July 1981 rehearsal recording, screaming her guts out. Such style.
When Carol was killed I became quite distraught. Things fell apart for about 15 months. After befriending Minimal Man's Patrick Miller in California and with the encouragement of both he and Don Fleming, I got back into the game. I moved to DC, decamped with the Velvet Monkeys, and made a final clutch of Boat Of recordings that overtly presaged the shift to a new performance identity, Peach of Immortality.
Boat Of's mix of influences was quite broad, and as acutely insular snobs we were very protective of them. We never revealed much of this sort of info, knowing intuitively that one quickly becomes trapped by pronouncements of aesthetic fealty. As a collective, we were sui generis. That may seem arrogant, but it's clear that we were doing something well outside prevailing norms. We were also hyper-critical - if we felt ourselves lapsing into any sort of lazy trope we tended to purge ourselves of the offending notions until they'd been expunged.
The archive is rather extensive - about 65 hours of material altogether. A few cassettes of backing tracks and performance edits disappeared between 1983-1984, and another was borrowed by a label guy (Peter from Armageddon / Press) who never returned it. Cunt. There was also a pretty amazing early rehearsal (September 1980-ish) tape that just vanished. But, remarkably, everything else survives.
- Tom Smith, March 2018
Boat Of: Mike Green, Carol Levy, David Gamble, Sandra-Lee Phipps, Jim Walker, Dominique Amet, Davey Stevenson, Don Fleming, Tom Smith, and others.
Part One:
Boat Of, live, 40 Watt, Athens, March 9, 1982 > Boat Of, live, 40 Watt, Athens, May 16, 1981 > Boat Of, live, Coffee Club, Athens, January 30, 1982 > Boat Of, "Bra" cassette radio cut-ups, Seaside, August 1983 > Boat Of, live, Coffee Club, Athens, January 14, 1982 > Boat Of, live, d.c. space, Washington, March 10, 1983 > Boat Of, live, House of Rimbaud, Athens, August 6, 1982 > Boat Of, If You'd Like to Nominate Your Boss remix, WABR studios, Tifton, July 23, 1982 > Boat Of, rehearsal, Cobb Institute, Athens, July 21, 1981 > Boat Of, Los Fabulosos 20 cut-ups cassette, Seaside, September 1983 > Nest (adj.), rehearsal, Cobb Institute, Athens, October 23, 1980 > Nest (adj.), rehearsal, Cobb Institute, Athens, October 27, 1980 > Boat Of, live, Night Gallery, Athens, July 19, 1981 > Boat Of, live, Night Gallery, Athens, September 22, 1981 > Boat Of, live, Night Gallery, Athens, October 24, 1981 > Boat Of, live, Nitery Club, Atlanta, January 17, 1983.
(29:58, contiguous)
Part Two:
Boat Of, ADS Sound session, Atlanta, February 14-16, 1983 > Pre-Cave, Cobb Institiue session, September 9, 1980 > Pre-Cave, From Writing "Indifference" session, Cobb Institute, Athens, July 1980 > Boat Of, Peach Encroachment sessions, Velvet Monkeys rehearsal basement, Washington, July 1-8, 1984, (the final Boat Of recordings) > Prepared Party, shortwave manipulation, Adel, October 1979 > Boat Of, rehearsal, Night Gallery, Athens, July 18, 1981 > Pre-Cave, Tom (magazine) interview, June 13, 1980 > Boat Of, soundcheck, T.V. Dinner, Atlanta, May 22, 1982 > Boat Of, live, T.V. Dinner, Atlanta, April 24, 1982 > Boat Of, live, Tyrone's O.C., Athens, June 11, 1981 > Boat Of, WABR session, Tifton, January 16, 1983 > Boat Of, WABR session, Tifton, November 30-December 1, 1982 > Boat Of, WABR session, Tifton, March 7, 1983 > Boat Of, live, WREK, Atlanta, September 5, 1982 > Boat Of, live, WREK, Atlanta, January 16, 1983 > Boat Of, live, WREK, Atlanta, August 29, 1982 > Boat Of, live, Wax Museum, Washington, March 11, 1983.
(29:51, contiguous)
Edited, mixed and produced March 2018 by Tom Smith, who looped and sorted the tracks via randomizing algorithms.
Original recordings composed and performed by the various iterations of Boat Of / Nest (adj.) / Pre-Cave / Prepared Party, 1979-1984.
Friday, March 23, 2018
Convalescence: Day Fifteen
A brief programming note: Kevin Drumm's new Karl Schmidt Verlag album, Jury Prize, is live and available at KSV Bandcamp. It's both a colossal return to KD's brutalist mid-aughts form and very much of the fractious moment.
There's no physical edition yet, as bounding up the stairs of Deutsche Post with armfuls of parcels is pretty much an impossibility - I'll be on crutches for another month.
Thursday, March 22, 2018
Convalescence: Day Fourteen
Hope they get a cool million attendees in DC on Saturday...
Wednesday, March 21, 2018
Convalescence: Day Thirteen
This is brilliant.
From the Guardian:
From the Guardian:
"Describing the suspension of (Nacho Carretero's Fariña, a 2015 expose of drug trafficking in Galicia) from sale as as a "disproportionate and anachronistic measure … to prevent people from reading the story", the Booksellers Guild of Madrid has launched the website Finding Fariña which uses a digital tool to trawl through the text of Don Quixote to find and highlight the 80,000 words that make up Fariña, allowing users to read the book despite the ban."
Tuesday, March 20, 2018
Convalescence: Day Twelve
Looking through my reactivated Facebook profile for hi-res images of Boat Of, the group Mike Green and I founded in Athens, GA. We ruled from (J.) Conradian redoubts from '79-'83, and I've once again become immersed in our simultaneously cosmopolitan, sectarian world. As I finalize the master for the forthcoming Forbidden Mourning Practice compilation, I become ever more aware of the debt I owe to Mike, Carol Levy, Sandi Phipps, David Gamble, Kim Karelson, Jim Walker, Leslie Michel, Davey Stevenson, Dominique Amet, Arthur Davis, Todd Ploharski, Vic Varney...
So far, I've only uncovered low-resolution images from the FB timeline. Bummer. Wanna see a few of them?
Early 1981, rehearsing at the Cobb Institute with Thomas Abdu (sadly out of frame), yours truly in the checks, and Mike Green.
Late '82, atop Vanessa Briscoe's bed. Davey Stevenson is well fit on the left, I've got some sort of perm going to match my red shoes in the middle (I wish I'd been a bit less antithetical in an obvious regard), and the explosively wry Dominique Amet.
A Polaroid collage from the early autumn of 1981, from locations around Athens. David Gamble, Sandra-Lee Phipps, Carol Levy, and myself.
A flyer for what turned out to be an extraordinarily raucous Coffee Club performance. Before our CC gig we invaded the stage during Love Tractor's set at the 40 Watt and assayed a convulsive half-hour improvisation. Officers from Athens-Clarke County Animal Control arrived much too late to disrupt the assault.
February 1983, Atlanta. Neither Carol Levy nor Jim Walker were able to make the gig, so David Gamble invited Birmingham pals Jim Bob & the Leisure Suits (half of whom later morphed into Primitons) to tackle my beautiful music loops. It would prove to be Boat Of's final gig in Georgia.
Carol Levy's flyer for our July '81 performance at Athens' Night Gallery.
Boat Of live at the Night Gallery, July 19. 1981. Sandi Phipps and I are at the far left; David Gamble is shirtless, and Mike Green's shadow forms a V for viaticum. Carol Levy was out of frame. Or, standing next to Mike without her guitar, which can't possibly be correct. (Photo by Linda Hopper.)
KD Returns to KSV!
Hello Droogs,
Kevin Drumm and I picked up our conversation - one that surges, drifts off, abates, and swells with elliptic certainty every few months - in the orthopedic ward of a hospital. He was in Chicago, and I was recovering from leg surgery (broken fibula) in Hannover. We were shooting the breeze, discussing Blue Öyster Cult, better names for kids (we settled on Four-Hour Binaural YouTube), Windy City rents, our 2011 tour (which we both enjoyed tremendously), and muzak-making.
Coming Friday, a new KD album on Karl Schmidt Verlag.
Pre-wire your jaws, as they're bound to plummet.
KSV Soundcloud preview link: here.
Kevin Drumm and I picked up our conversation - one that surges, drifts off, abates, and swells with elliptic certainty every few months - in the orthopedic ward of a hospital. He was in Chicago, and I was recovering from leg surgery (broken fibula) in Hannover. We were shooting the breeze, discussing Blue Öyster Cult, better names for kids (we settled on Four-Hour Binaural YouTube), Windy City rents, our 2011 tour (which we both enjoyed tremendously), and muzak-making.
Coming Friday, a new KD album on Karl Schmidt Verlag.
Pre-wire your jaws, as they're bound to plummet.
KSV Soundcloud preview link: here.
Monday, March 19, 2018
Convalescence: Day Eleven
Completed the final side-long mixes for Forbidden Mourning Practice, the forthcoming Boat Of compilation tape on Hitomi Arimoto's 777 Was 666 imprint.
Took my first extended stroll through the neighborhood since returning home from the hospital. Astounded I can walk on my right leg so soon after surgery and implantation of a metal plate, screws, boatswain's pipe, etc.
Took my first extended stroll through the neighborhood since returning home from the hospital. Astounded I can walk on my right leg so soon after surgery and implantation of a metal plate, screws, boatswain's pipe, etc.
Sunday, March 18, 2018
Convalescence: Day Ten
Healing apace, can't complain.
We finally got round to watching Ingrid Goes West. Brutal, hilarious, brilliant.
We finally got round to watching Ingrid Goes West. Brutal, hilarious, brilliant.
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Happy New Year from the Harz...
Hello Droogs, Happy 2019! I'm in the Harz region of Germany, enjoying a three-day getaway to cap off an eventful year, one marked by celeb...
A special Soundcloud mix created from the final moments of four of the nine performances featured on the new Sensationists compilation ...
"Shelley Rene: Stark Friggin' Lodestar" (This profile of the pioneering USENET nude model was written for Creative Loafing ,...


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Instructions below
Video Instructions
Our spokesmonkey Ezriah Zippernowsky has made a series of videos showing how to use ezyZip. It's eeeeeasy!
If you are looking for a quicker compression program with the best archiving features (e.g. encrypt data, image size reduction & watermarks, remove personal data from files, convert doc to pdf, share in the cloud and more), then you should check out latest version of WinZip. Download WinZip from here
How to convert rar to ithmb file?
- Under "Select rar file to convert", click on browse (or your browser equivalent)
- Select the file you wish to convert.
- Click "Convert to ithmb". It will list all the ithmb files in the rar archive.
- IF your archive is password protected, enter it at the prompt and then click "Set Password".
- Click the green "Save" button to save individual ithmb file to your local drive.
Video Instructions
In this how-to video, our spokesmonkey Ezriah Zippernowsky demonstrates how to convert rar to ithmb. This example uses a jpg file but the same steps apply to ithmb files.
What operating system and browser does ezyZip support?
ezyZip supports any OS that can run a modern browser. We have tested it to work with Windows, MacOS, Linux (e.g. Ubuntu, Mint, Debian), Android, ChromeOS (Chromebook), iOS (iPhone, iPad & iPod Touch).
Ensure you are using the latest version of one of the popular browsers or their variants. (e.g. Chrome, Firefox, Safari).
Please let us know via the feedback form if you have any issues.
Ensure you are using the latest version of one of the popular browsers or their variants. (e.g. Chrome, Firefox, Safari).
Please let us know via the feedback form if you have any issues.
What is ezyZip?
ezyZip is a free online utility for extracting ithmb files from a rar file. No need to install additional software as it runs in the browser. It supports a bunch of other file extraction and conversion options too.
Unlike other online zip conversion utilities, ezyZip does not require you to upload or download files to a server. It runs locally as a browser app, thus making it much quicker than other similar online conversion tools. There are no file size limits! This also ensures your privacy will be protected as no file data will leave your browser.
What is a ithmb file?
The .ITHMB extension stands for iPod and iPhone Photo Thumbnails File and was developed by Apple.
What is a rar file?
A rar file is a collection of files & folders wrapped into a single package and compressed using the Roshal Archive algorithm. It was first released by Russian software engineer Eugene Roshal in 1993. It purports to have better compression speed, encryption and error handling than the ZIP format.
It is a common file format used primarily to bundle multiple files for easier distribution or backup.
It is a common file format used primarily to bundle multiple files for easier distribution or backup.


text:
August 1, 2014
This piece was adapted from a June 10 presentation at PRSA's Travel and Tourism Conference in Tampa.
Being featured on TV is a great way to gain exposure for your brand, so it's important to know how to tell your story through sight and sound. It's hard to land a popular production, so make sure that you have a compelling story and a unique backdrop.
Here are some basic tips for making the most of your chance to work with a production company.
Please log in to MyPRSA to read this article, as well as to view and leave comments.
Learn more about PRSA membership, and join a professional network you can count on.


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We are pleased to announce that we will be starting a new venture in April called the
Spotlight English Club
Wednesday 11th April 10:30am – 12noon
This is an English Conversation Club intended for those whose first language is not English and is open to anyone in the community who want to practise their spoken English.
During our time together we will listen to a 15 minute broadcast made by Spotlight covering everyday subjects after which everyone has the opportunity to chat and discuss what they have heard.
There will also be a social aspect to the club including refreshments. Everything is completely FREE OF CHARGE.
Our first group will be on Wednesday 11th April at 10:30am in the main hall of our church. You can either register on that day or if you would like further information you can contact our Pastor Gareth, on 01302 376233.
The group will run during term time so please check the events calendar for updates.


text: 'Big Mouth': TV Review 11:09 AM PDT 9/28/2017 by Inkoo Kang FACEBOOK TWITTER EMAIL ME YOUTUBE A terrific comedy that pushes boundaries with thoughtfulness. TWITTER 9/29/2017 Netflix's latest animated series is a grownups-only cartoon about puberty voiced by Nick Kroll and John Mulaney. "Everything is embarrassing": It's no longer just a mantra liberals repeat to themselves while watching the latest news about the White House. That unrelenting sense of discomfort and shame fuels Big Mouth, Netflix's adult cartoon about that early phase of puberty when it feels like time only exists so that each new minute can present its own opportunity to make you feel bad, confused or both. Sweet, progressive and breathtakingly filthy, the latest collaboration between comedians Nick Kroll and John Mulaney recalls the emotionally grounded squirminess of the boys of Freaks and Geeks and the sex-positive yet debasement-obsessed endocrinological chaos of, well, nothing I've ever seen. When I went to college in the early 2000s, I was astounded that several of my acquaintances had no idea who Bart Simpson was — their parents had forbidden them from watching anything as dirty as The Simpsons. I can only imagine what those parents would make of Big Mouth, which is essentially a comedy about a group of horny suburban 12-year-olds whose lives revolve around getting to know their genitals better. The dilemma that faces four-eyed middle-schooler Andrew (voiced by Mulaney) in the first episode is typical of the series' candor and existential self-searching. Sleeping over in his bestie Nick's (Kroll) room, Andrew avers to the Hormone Monster (also Kroll), a furry green beast with a penis for a nose, that he won't masturbate with his friend sleeping next to him. "I'm a good person," Andrew says. Then, feeling his resolve melting, he wonders, "What the hell is wrong with me?" The Hormone Monster is nonplussed: "You're a perfectly normal gross little dirtbag." Big Mouth follows dorky Nick, nerdy Andrew and tart-tongued Jessi (Jessi Klein) as they suffer mundane rites of passage — dates, dances, periods, slumber parties, boyfriend/girlfriend expectations — with extreme yet relatable awkwardness. Seemingly inspired by Kroll's bulging eyes and fleshy lips — the character named after the actor gets teased for his "giant blubbery looks" and "big, weird catfish mouth" — the animation style is somewhat crude but charmingly ugly-cute. It's exactly the aesthetic you'd want for an irreverent body-horror cartoon that's at heart about the innocence of children. Icepick-sharp pop-culture commentary and surreal flights of fancy — in which tampons sing, vaginas educate and penises play basketball by ambulating on their bristly balls — round out the humor. Still, it must be admitted that there's nothing particularly groundbreaking about exploring male anxieties about the body. That's why the storylines about Jessi and, to a lesser degree, studious Missy (Jenny Slate) feel fresher and more distinctive. The Hormone Monstress (Maya Rudolph) pushes Jessi to act out in cannier ways than the boys do, and the abruptly strained relationship the girl shares with her mother (Klein), who struggles with her own significant issues, gives the season a poignant emotional arc. "Is there anything good about being a woman?" Jessi asks the Hormone Monstress with exasperation at one point. (As usual, the answer's in her pants.) Fred Armisen and Jason Mantzoukas play to type as, respectively, Nick's too-affectionate father and a mini-skeeze heading toward a lifetime of self-dooming misogyny. Big Mouth strives to avoid the usual parental wisdom doled out by sitcom moms and dads, but errs with the inclusion of the ghost of Duke Ellington (Jordan Peele), a hard-partying poltergeist haunting Nick's house that occupies the outdated wacky-neighbor role. Nearly all 10 episodes run a little long at 25 minutes, but with the joke density so high, chances are you won't mind. Even better than the laughter that Big Mouth elicits might be the relief that most viewers have passed that age when each new day brings with it a different way for the soul to shrivel. We'll never be young again — thank mother-bleeping goodness. Cast: Nick Kroll, John Mulaney, Maya Rudolph, Jason Mantzoukas, Jordan Peele, Fred Armisen, Jenny Slate, Jessi Klein Creators: Nick Kroll, Andrew Goldberg, Mark Levin, Jennifer Flackett Premieres: Friday (Netflix) FACEBOOK TWITTER EMAIL ME YOUTUBE Inkoo Kang email@example.com @thr


text: From Aerandria Scans: It's the 16th century and the knights of the Mediterranean country Malta take pride in being the strongest in the world. Aciel is a beautiful lady-knight who gradually makes her way into the group of the knights, despite the fact it's forbidden for women to be knights. Learn the tale of the magnificent knights whose charms neither friends nor foes can resist!


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FinTech Connect 2020
2nd December, 2020 |
Head of Technology
Carlos oversees the operations of TPL. Prior to joining TPL Carlos was the Service Operations Manager at Kalixa Payments Group. Carlos also has experience in the gaming space having worked for Party Gaming and its subsidiaries. His skills and experience include payments, processing, risk management, IT, reporting and AML among others.
Ready to work with us?
Payments Made Simple! Our mission is to become the global leader in providing payment service solutions to Financial Institutions, Fintechs, MNOs and Governments. Transact Payments provides a number of payment solutions with which we can support you.
So get in touch today to see how we can help.


text: Boyo Posted May 18 Enhancing Map Movement: Sprint vs Sphere Sprint increases the user's forward movement speed. Sphere shrinks the user's player model. When players sprint, they are still traversing the same paths, just doing so a little faster. When players transform into a ball bearing, they don't move any faster but they do gain access to a set of previously inaccessible routes. Doggy doors are too big for bipeds but still allow a smaller sphere to roll on through. Sprint wins the Accessibility round, being a mindless button that anyone can mash to go fast. Sphere wins the Depth round, giving players the ability to out-think their opponents rather than simply out-run them. Quote Share this post Link to post


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Dimension Films has released a theatrical trailer for their upcoming horror thriller Aftershock. The film is directed by Nicolás López and is based on a screenplay by López and Guillermo Amoedo. Aftershock stars Eli Roth, Andrea Osvárt, Ariel Levy, Nicolás Martínez, Lorenza Izzo, Natasha Yarovenko, and Selena Gomez. The horror film will open in theaters on May 10th.
This film takes place after an earthquake erupts in Chile. Visiting tourists soon discover that a neighboring prison in the area collapsed in the event, and all surviving criminals managed to break free. The stranded tourists soon learn that the most terrifying thing, more threatening that Mother Nature, is what she created.
Source: Dimension Films


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campaign is all about touring the world, amassing fans, and selling out -- if you're into that sort of thing. This is the first time we're seeing meaningful narrative choices in a Rock Band game, and the direction you take your band dictates the shows you'll play, the places you'll visit, the gear you unlock, and the money you earn."When we started looking at all the new features we have in the game, mechanically, it just made sense for us to build this epic, branching story where instead of taking one rise to fame path through the world," said Designer Alli Thresher. "You know, you go from your hometown to being the biggest band in the world, you choose…what kind of band you are."
see deal
Rock Band 4 - PlayStation 4$59.99on Gamestop
Rock Band 4 is a straight-up role-playing game that has more in common with the superb 80 Days than any previous Rock Band campaign -- and it's the first one I'll play for any meaningful amount of time."It really deepens the band fantasy, and it really gives us the opportunity to answer some things we've been hearing from fans over the last five years and really, really amp up that feeling and the fantasy and dynamics of being in a band," said Designer Alli Thresher. "Making decisions together, charting a path through your careers, building your story as a musician, and figuring out who you are."
This means making tough choices about the kind of band you're trying to build. "You can take corporate gigs and make a lot of money as a band, you can take a path to pursue your artistic integrity, and along the way, as you make these choices, the game kind of responds to you," Thresher explained. "So, you might take a gig where you decide you are the spokesperson for off-brand salted meats and start your every gig by warming up the crowd telling them how much you like salted meats. And the crowd is not into it and booing and stuff, and you have to play really, really well to get them over it."
That sort of crowd hostility plays into your career regardless. Not everyone likes every band, so you may end up playing a show for a crowd that isn't into you. Winning them over takes skill. Failing out of a song is easier when the crowd already has a notion about you, so playing well is necessary to staying in it as well as winning those haters as fans.On the other side of the coin, Thresher said, "you could take a path where maybe you decide you just want to, like, couch surf around the country, use social media to meet people and sleep on their floors. So, you're not really making a lot of money, but maybe meeting enthusiastic crowds – maybe too enthusiastic – maybe meeting super fans and trying to navigate dealing with them."
Less money means fewer guitars and character customization gear, but potentially better renown. It's a series of risks, with each gig serving as your quest. Complete it, get loot for each member of your party, and move on better than you were before. You may encounter interesting challenges along the way, and the payout is worth the struggle.
Previously, Thresher admitted, fans meant very little. Their capital carried little weight. In Rock Band 4, "you accumulate fans per geographic location across the world, and fans gain you access to new opportunities that unlock special, cool – we're still working on it – but special Easter Eggs and that kind of thing. So, if you have fans in a certain region, you might be able to have a cool metal gig, you might have a big set list, you might see avenues you haven't seen before."
You start in your hometown, but grow into a worldwide phenomenon, whether through intense commitment to your band or your label and sponsors. Your global tour could take you to entirely different continents from one play through to the next, and that's really exciting. I replayed 80 Days to see what mysteries awaited in cities I skipped last time. To have similar structure in a cooperative Rock Band setting, where bandmates can bicker about the sort of story we want to tell for ourselves, the sort of legacy we want to leave, gives Rock Band 4's story mode meaning for the first time.
I'm going to buy so many leather jackets and spikey boots...
For more, check out Everything You Need to Know About Rock Band 4.
Mitch Dyer is an Editor at IGN. He hosts IGN Arena, a podcast about MOBAs. Talk to Mitch about Dota 2, movies, books, and other stuff on Twitter at @MitchyD and subscribe to MitchyD on Twitch.
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In This Article


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Thiruvananthapuram (Kerala) May 20: In a brave act of pure self defence, a woman cut off a man's genitals after he allegedly tried to rape her at Pettah.
The seriously injured man was admitted to the hospital following the incident which took place last night.
As per the police, the man was known to the woman and her family and also used to visit her house to conduct pujas.
The woman, in her complaint, alleged that the man was harassing her for last two days.
A case has been registered against the man Protection of Children from Sexual Offences Act (POCSO) Act. However, no case has been registered against the woman. (ANI)


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The "What's Up Wednesday" blog hop has ceased to be, but round-up posts are fun, so here's a new format.
The absence of "June gloom" after such a lovely May. The warmth and sunshine lures me outside onto the deck, where we grill dinners and play with the neighbour's cats, who love to visit. Lucas and Jake (but especially Lucas) are partial to me, and will abandon my husband mid-pet if I go outside. How is it that cats make this feel like an honour and a privilege?
On Audible: just finished Book 8 of the Dresden Files series, narrated by James Marsters, and have plunged into Northanger Abbey, narrated by Juliet Stephenson. I cannot praise either of these narrators highly enough; they are flat-out marvelous voice actors.
In print: just purchased Rachel Aaron's 2,000 TO 10,000 after hearing her interviewed on the DBSA podcast, and have dipped a tentative toe. So far so good!
…listening to
Two albums by Vancouver musician Bodhi Jones, who has a song ("Suitcase Packed") in rotation on CBC radio and is working on a third album to be released soon. He's crowdfunding the costs of engineering, publicity, etc., with an indiegogo campaign, and my hubs and I met with him this past weekend to check out his business savvy before we decide how much to throw into the campaign. He's a really engaging guy, grounded and sensible in addition to talented. Go check him out and support his efforts if you like the tunes
I've been Netflixing Columbo, a favourite from my early teens. I've watched the first two seasons and the beginning of the third, and so far there hasn't been one that I remember. I guess, given that I was only about nine when the series started, I was in bed before it came on for the first few years. But boy oh boy do I remember the cars! The shoes! The hair! The fashions! I get all gleeful bouncy just seeing the costumes and set design. And the guest stars, those sanguine, murderous guest stars; they're like the constellation of Hollywood of My Childhood. Some of them (e.g., Ray Milland, Roddy MacDowell) were in old movies, some (e.g., Martin Sheen) were rising stars, and some of them (e.g., Robert Culp) hit it really big in the next decade. I get all the warms just watching those familiar faces try to dupe the shlubby Lieutenant.
…looking forward to
I'm off to Toronto on Thursday, for the Editors' Association of Canada's first international conference, Editing Goes Global. While I'm there, I will be attending numerous sessions (of course), networking like a demon, speed mentoring with two great editors, and (with good luck) getting together with my friend Brad, who will be in town for the Indy race that's on the same weekend. I bought some new clothes today, in preparation. I'm planning to travel with just a carry-on bag, so everything squishes really small.
Grammar assignments from the course I'm taking. I also did a brain dump of about 2000 words on a paranormal story involving ghosts, which has been percolating in my brain for years. I still don't know where it's going, as a story, but "from brain to electrons" is a good start.
…making me happy
I had my first gig as co-host of the TWS Reading Series last Thursday. The reading series arose out of The Writer's Studio, the creative writing program I was part of last year, and has been going for several years. Its purpose is to give TWS students an opportunity to read their work in public, and to showcase and promote other local and Canadian authors who might happen to be touring to promote a book, etc. Thursday's lineup was great, and I look forward to more great evenings like it during my tenure as co-host.
That's a big round-up. Here, as a treat for reading so far, have a photo of an elephant and a moose together. (That's our travel companion, who insisted we call him Twigbok while were were in Africa.) This elephant was the first wildlife we saw on the drive from the airstrip to the safari camp.
Teehee, that's so cute that the cats love you so much. Hope S wasn't offended to be abandoned mid-pet!
That 2K to 10K book sounds really useful.
Have a blast at the conference! :):)
Not offended but surprised, because cats usually prefer him.


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How do we book you for our wedding?
Get in touch with me to check if your date is free, I am more than happy to meet up and show you my albums and chat about your wedding photography for your big day. Then I require a booking form to be completed and signed with a retainer of £300 to secure your wedding date.
How would describe your photo style?
I love bright and natural images. I edit all images as true to real life, except for a few creative images, which I may edit for impact or mood. I also shoot documentary images along with a small amount of directed family and bridal images, relaxed and editorial respectively.
Do you shoot in Colour or Black and White?
I shoot everything in Colour and choose some images to be edited in Black and White for the mood. Any Colour image can be changed into Black and White.
How would describe your work style?
I am a natural people person so I am easy to work with and very approachable. I bring a 'can do' attitude to weddings and great humour which make people relaxed. I dress like a guest so I will not stand out in your wedding day.
Can I customise a collections based on my needs?
I have 4 base collections Essential, Elegance and Exquisite, if you need something more bespoke just get in touch.
What travel costs are covered?
I am happy to travel up to 75 miles from Belfast without extra charge. If your wedding is further away let me know when enquiring.
Do you have backup equipment?
I shoot with Canon cameras and have done for the duration of my career. I carry backup camera bodies and lenses to cover every eventuality.
Are you insured?
I have public indemnity and liability insurance.
Wedding day
Can I give you a specific list of shots I'd like from my wedding?
Yes, at our pre-wedding meeting I will go through family groups, detail images and any other images you would like. I'll aim to get these images where possible.
What happens if you can't make it to my wedding day due to emergency or illness?
I am a full member of the Professional Photographers Association of Northern Ireland and have the support of over 40 photographers who cover weddings in these situations. Keep in mind this is a rare case for any photographer.
Is it okay if guests take photos while you are taking photos?
Totally, your guests are family and friends so I have no issue at all. I do like to take a couple away for a short time for some intimate images and with no-one to distract them.
What happens if it rains?
I'm used to working on changing conditions, many locations have a various options for bad weather.
Do we need to feed you on the wedding day?
I do not ask to be fed but need to know whether you are feeding me or not so I can make arrangements. If you are feeding me, bar food is enough though we are happy to sit in the main room if you wish.
Post wedding
How long after the wedding will we receive our proofs, our digital images and our album?
I aim to have proofs back within 3 weeks and edited images within 3 weeks after that. Sometimes I am faster and sometimes a little late depending on wedding season. Album delivery varies but after design sign off (for Elegance and Exquisite) the albums are back from Italy between 2 to 6 weeks.
How many images do we get from our wedding?
I focus on curating a great wedding story for our couples and deliver a selection of around 450 to 750 photos depending on the length of coverage, access to locations and weather.


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I've been meaning to post this story now for over two years. It's more out of a sense of duty and completeness to the trip I had that I write this now. My trip ended in August 2013, and I feel like I never really wrapped up this blog, or told some of my final thoughts and memories of traveling around the world for a year. I'm going to attempt to wrap things up with the next couple posts that talk about some experiences I never got around to talking about, as well as talk about my thoughts of being back.
Without a doubt, the craziest story of my trip involves somewhere around the midway point in my trip to Thailand. So here it goes…
I arrived in Thailand after being in India for about three weeks. India was pretty wild, and felt like a different trip to me. I've never felt so foreign in a place in my life as I did India, and might have to recount more of my experiences there. Compared to India, arriving in Bangkok, Thailand felt like I was in any Western country at first. The airport, roads, buildings and infrastructure were all very modern, at least in appearance. I spent my first week in Bangkok in a hostel. I had an awesome time in Bangkok. The hostel I was in was small, and I had no trouble meeting other travelers to go exploring with. I did all the classic tourist things in Bangkok… I went to the temples, I walked around the markets, I ate Thai street food, and just had fun exploring Bangkok. After about a week, I left for Chiang Mai which is a city in the North. I stayed at yet another hostel that was filled with the usual… Brits, Aussies, and some Canadians and Americans. I did a day long cooking class here that was fun. I also went on a jungle trek for three days that was really cool. A lot of hiking, and we stayed in local villages and slept in bamboo huts. If I haven't written about that, I'll need to.
Prior to leaving for my jungle trek which was just outside of Chiang Mai, I had met some other travelers planning to ride motorbikes to a sleepy mountain village called Pai. Pai is kind of known as this chilled out place that's very touristy. It requires getting on a bus from Chiang Mai for a few hours. My new hostel buddies were planning on checking it out, but wanted to make more of an adventure out of it by renting motorbikes. This would allow them to see more of the countryside, and stop at various places and check things out. They were planning to leave the day after I got back to Chiang Mai, so I might have a chance to join them. Now at this point, I should say a few things:
- I don't know the Thai traffic laws, and don't have a license
- I've never ridden a motorbike, scooter, or anything remotely close in my entire life
- Pai is roughly 84 miles from Chiang Mai
Ok, so what would make me think I could ride a motorbike for the first time ever in a foreign country where they drive on the opposite side of the road of what I'm used to? Well, I think at the time, I had been on the road for 8 months, and nothing really scared me. I was looking for adventure and to do something different…. really different. Riding a bike in Thailand sounded like fun. I liked the people I had met in the hostel, and the whole idea just seemed cool. So after getting back from the jungle trek, I found my friends were still planning the trip, and so I joined them.
The day started by going to the rental bike place. The plan was to pay them to transport our bags up to Pai, and then we'd get them back (along with our passports) when we arrived in Pai. So see… this was an actual service that was provided… lots of people do this in Thailand, including idiots like me probably. We got our bikes, and one of the guys in our group, Sam from Australia, gave me a quick tutorial. At the time, Sam also commented that it looked like a had really nice and fast bike. Foreshadowing. After my little tutorial in working the gas, brake, and gears (thankfully it was an automatic, or maybe I might have been able to end the trip right then and there), we were off. I should also probably point out that this bike was more of what we would call a scooter in the States.
Our first stop was to get gas. As we set out on the busy streets of Chiang Mai, my first thoughts were… "What the hell are you doing? This is a little nuts". However, after a few minutes and some turns through intersections, I was starting to relax. We got to the gas station (which looked like just about any other gas station I've seen in the US), filled up, and then headed out again. I was starting to get comfortable on the bike, and by the time we were outside the city, I felt like this was going to be a fun day. Riding in the countryside was beautiful. We saw landscapes, waterfalls, and plenty of Buddhist temples. Riding our own bikes gave our group the ability to stop and see things along the way as we wanted… total freedom to explore, and I was thinking, "Wow, what an awesome experience". That was what my trip had become at that point… collecting more amazing experiences. I didn't really care about tourist sites anymore. I had seen enough amazing stuff at this point that I was overstimulated and needed to do more adventurous things to get the same thrills I had earlier on in the trip. Probably about a little past the halfway point on the trip to Pai, we found a roadside cafe, and stopped to eat. Our group was small from what I remember. Other than Sam, I actually don't remember the names of anyone else at this point. I remember there being a girl from Austria, but I can't remember if there was one or two more other people with us. I didn't take many photos that day, and I honestly can't even see the face in my mind of the other person I kind of remember. Sam and the Austrian girl were leading us since they seemed to know the way and had tons of experience on bikes.
After the cafe, we rode a little further and found what in the States would be a National Park. It even had one of those big brown wooden signs with yellow lettering you find in US Parks.
There was this waterfall, and we actually took the chance to get out and get into the water. We wouldn't have had this experience on a bus. We would have just arrived in Pai, and hung out, but nothing else. It might have been fun, but it wouldn't have been the experience we were now having this day.
At this point, I was feeling pretty chill. We had been riding our bikes for what felt like all day. We had stopped at several places, seen some cool sites, swam underneath a waterfall, and just generally enjoyed the experience. I was pretty comfortable on my bike at this point, and glad I made the decision to join my hostel buddies on the this trip.
After the waterfall, we got back on our bikes with the plan to continue riding without any more stops to Pai. Probably half an hour to 45 minutes after leaving the waterfall, we were getting into some mountainous terrain. The road was getting really curvy and a little dicey. Also, I had been riding for a while, and was probably going a little too fast. Not knowing how to properly handle turns on a bike, I wasn't properly leaning into turns and letting the my body and bike do the work. I was over turning the steering, and on a really tight turn, it caught up with me. I just remember this point where my bike slid out from under me. I was probably only going 25 mpg, but bike when sideways, and I hit the pavement hard on my left side. My left knee and arm took the brunt of the fall. The bike slid in a straight line from where I had lost it, and I just barrel rolled, tearing myself up along the way. Luckily, I had a helmet on, but I don't think I hit my head anyway. When things came to a stop, I just remember thinking, "You're an idiot". I looked down to assess the damage, and I saw what was probably the worst gash on my knee I've ever seen. I mean, my knee basically opened up and I think I could see my knee cap. I looked at my left arm, and there was just a huge road rash down my entire forearm. Both of my hands were torn up pretty bad too. However, I noticed right away that I was able to stand which made me think I hadn't broken any bones. It was probably the only good thing I could find at that point. I knew I couldn't go any further with the trip. I was so banged up, and sore. I also realized that my glasses had fallen off in the crash. I started looking around, but couldn't find them. Luckily, there was someone in our group riding behind me (think all the others were ahead). Eventually, Sam and the Austrian girl realized I wasn't with them, and rode back. I felt so bad for wrecking the day like that for them, because now I had put them in a situation of having to help me which I hated. I went over and checked out my bike, and other than some scratches, it seemed ok. I looked at my knee and just couldn't believe that was a part of my body. It looked like a mess, and would absolutely require medical attention. But where? I was in the middle of what felt like a Thai jungle with the worse injury of my life. I didn't want to panic, but I just didn't know how this was going to work out for me. It's actually kind of hard to write about this now because it's all starting to come back. What an awful and pitiful situation I found myself in. I think I'll stop here for now, but promise to pickup the story in another couple days. Promise!