Staircases, dominoes, and the growth rate of 1324-avoiders

We establish a lower bound of 10.271 for the growth rate of the permutations avoiding 1324, and an upper bound of 13.5. This is done by first finding the precise growth rate of a subclass whose enumeration is related to West-2-stack-sortable permutations, and then combining copies of this subclass in particular ways

Computerized clinical decision support for the early recognition and management of acute kidney injury: a qualitative evaluation of end-user experience

Background - Although the efficacy of computerized clinical decision support (CCDS) for acute kidney injury (AKI) remains unclear, the wider literature includes examples of limited acceptability and equivocal benefit. Our single-centre study aimed to identify factors promoting or inhibiting use of in-patient AKI CCDS. Methods - Targeting medical users, CCDS triggered with a serum creatinine rise of ≥25 μmol/L/day and linked to guidance and test ordering. User experience was evaluated through retrospective interviews, conducted and analysed according to Normalization Process Theory. Initial pilot ward experience allowed tool refinement. Assessments continued following CCDS activation across all adult, non-critical care wards. Results - Thematic saturation was achieved with 24 interviews. The alert was accepted as a potentially useful prompt to early clinical re-assessment by many trainees. Senior staff were more sceptical, tending to view it as a hindrance. ‘Pop-ups’ and mandated engagement before alert dismissal were universally unpopular due to workflow disruption. Users were driven to close out of the alert as soon as possible to review historical creatinines and to continue with the intended workflow. Conclusions - Our study revealed themes similar to those previously described in non-AKI settings. Systems intruding on workflow, particularly involving complex interactions, may be unsustainable even if there has been a positive impact on care. The optimal balance between intrusion and clinical benefit of AKI CCDS requires further evaluation

Directional layouts in central lowland Maya settlement

This paper suggests the existence of non-random, directional patterns in the location of housemounds across the Late Classic Maya settlement landscape at Baking Pot, Belize, and then explores the wider implications of this patterning in the central Maya lowlands. It introduces an anisotropic method – based on nearest neighbour bearings and successive grid offsets – in order to explore possible rectilinear organisation in settlement layouts despite the presence of uneven and irregular patterns of archaeological dating and recovery. The results suggest a grid-like distribution of houseplots and, by implication, also a set of routes running throughout the housemound landscape and local Maya neighbourhoods during the site's Late and Terminal Classic history. Furthermore, different possible alignments in different parts of the site are tentatively regarded as an indication of shifting orientations to localised grids, following the shift in alignment of monumental architecture, as the settlement landscape expanded over time. Finally, we discuss the implications of these findings with respect to the broader interpretation of Maya settlement patterns

Passions before passivity, actions after self-certainty : binding the philosophy and neuroscience of affects

This thesis examines the turn to affect in both philosophy and neurobiology beginning in the 1990s. Both fields shared themes of a return to emotional aspects of the body; a rapprochement between natural sciences and humanities; and rethinking of causality, intentionality, identity and temporality. Yet the field remains contentiously divided. Disputes arise mainly from differences in understanding of key terms (notably between affect and emotion) and the place of the intentional subject within expanded, flattened conceptions of agency, causality and the animate/inanimate, differences ultimately between implications in and overcomings of past metaphysics of coupled opposites and the philosophy of the subject. Implication because conceptions of affect have been historically dominated by the active and passive understood as a doing and being done to; affects then become quantitative, external impositions disrupting purely self-present subjects requiring philosophies of defence that privilege sameness over difference. Whereas overcomings posit a pure activity or passivity, simultaneities of active and passive, or a non-temporal ‘before’ prior to activity/passivity. This thesis explores the alternative possibility that ‘active/passive’ never really translated the Greek ποιεῖν/πάσχειν that is its root and root of affect as translation of πάθος. The thesis is in two parts: in philosophy, I uncover a broader sense of πάσχειν as bindings of implicit differences prior to any explicit separation of agent and patient. Meanwhile, in contemporary neuroscience, action is being redefined through ‘prediction processing’ theories where error as the difference between world and an organism’s implicit models of that world motivates action. Affective neurobiology then describes this radical contingency of expectation and actuality in specifically affective terms as the organism in its self-difference. I conclude by binding the radical transformations in active and passive each turn effects to understand affect still as a pairing of active/passive but where these terms signify not an oppositional agent acting on patient, but as the binding of contingent, implicit differences with their making explicit through the affections of error in the organism’s necessary difference and togetherness with world

A structural characterisation of Av(1324) and new bounds on its growth rate

We establish an improved lower bound of 10.271 for the exponential growth rate of the class of permutations avoiding the pattern 1324, and an improved upper bound of 13.5. These results depend on a new exact structural characterisation of 1324-avoiders as a subclass of an infinite staircase grid class, together with precise asymptotics of a small domino subclass whose enumeration we relate to West-two-stack-sortable permutations and planar maps. The bounds are established by carefully combining copies of the dominoes in particular ways consistent with the structural characterisation. The lower bound depends on concentration results concerning the substructure of a typical domino, the determination of exactly when dominoes can be combined in the fewest distinct ways, and technical analysis of the resulting generating function

Plaque size is decreased but M1 macrophage polarization and rupture related metalloproteinase expression are maintained after deleting T-bet in ApoE null mice

BACKGROUND:Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. METHODS & RESULTS:We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND). Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS) and brachiocephalic artery (BCA) plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1), MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3. CONCLUSIONS:Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased

Long-Term Demographic Trends in Prehistoric Italy: Climate Impacts and Regionalised Socio-Ecological Trajectories

The Italian peninsula offers an excellent case study within which to investigate long-term regional demographic trends and their response to climate fluctuations, especially given its diverse landscapes, latitudinal range and varied elevations. In the past two decades, summed probability distributions of calibrated radiocarbon dates have become an important method for inferring population dynamics in prehistory. Recent advances in this approach also allow for statistical assessment of spatio-temporal patterning in demographic trends. In this paper we reconstruct population change for the whole Italian peninsula from the Late Mesolithic to the Early Iron Age (10,000–2800 cal yr BP). How did population patterns vary across time and space? Were fluctuations in human population related to climate change? In order to answer these questions, we have collated a large list of published radiocarbon dates (n = 4010) and use this list firstly to infer the demographic trends for the Italian peninsula as a whole, before addressing each of five sub-regions in turn (northern, central, and southern Italy, Sicily, Sardinia). We also compare population fluctuations with local paleoclimate proxies (cave, lake, marine records). At a pan-regional scale, the results show a general rapid and substantial increase in population in the Early Neolithic with the introduction of farming at around 8000 cal yr BP and further dramatic increases during the Bronze and Iron Age (~ 3800–2800 cal yr BP). However, different regional demographic trajectories exist across different regions of Italy, suggesting a variety of localised human responses to climate shifts. Population and climate appear to have been more closely correlated during the early–mid Holocene (Mesolithic–Neolithic), while later in the Holocene (Bronze–Iron Ages) they decouple. Overall, across the Holocene the population dynamics varied by region and depended on the long-term socio-ecological dynamics prevailing in a given area. Finally, we include a brief response to the paper ‘Radiocarbon dated trends and central Mediterranean prehistory’ by Parkinson et al. (J Word Prehist 34(3), 2021)—synchronously published by Journal of World Prehistory but wholly independently developed—indicating how our conclusions accord with or differ from one another

Mechanisms and Applications of RecA-independent recombination in Legionella pneumophila.

Recombination is fundamental to genome maintenance and contributes to diversity in all Domains of life by generating novel sequences from the breaking and joining of DNA. RecA is central to one of the best studied mechanisms of recombination, but RecA-independent pathways also have implications for genetic engineering, evolution, and DNA replication. Here, I harness two forms of RecA-independent recombination for engineering of Legionella pneumophila, while also probing replication and repair machinery. Specifically, I make unmarked deletions in L. pneumophila using the Flp site-specific recombinase while also examining single-stranded nucleases and mismatch repair. I also describe a distinct form of recombination that does not require expression of recombinase genes. Oligonucleotides (oligos) generate mutations on the L. pneumophila chromosome by a mechanism that requires homologous DNA, but not RecA, RadA or any known phage recombinase. Instead, DNA replication likely contributes, since oligo-induced mutagenesis required ≥ 21 nucleotides of homology, was strand-dependent, and was most efficient in exponential phase. Mutagenesis appeared to be distinct from previously described mechanisms of oligo recombination, as it did not require canonical 5’ phosphate or 3’ hydroxyl groups, but did require the primosomal protein PriA and DNA Pol I. After electroporation, oligos stimulated excision of 2.1 kb of chromosomal DNA or insertion of 18 bp, and can be exploited to generate chromosomal deletions and to insert an epitope into a chromosomal coding sequence. The frequency of mutagenesis also increased substantially when either its RecJ and ExoVII nucleases were inactivated or the oligos were modified by nuclease-resistant bases. L. pneumophila is a diverse species and has a surprising number of Eukaryotic-like genes. As the organism is naturally transformable, it is thought that the species acquired some of these genes by horizontal gene transfer. Since divergent Eukaryotic sequences may be inefficiently incorporated into the genome by RecA-mediated recombination due to the extensive homology required, oligo-induced mutagenesis may have evolutionary implications as a mechanism to incorporate divergent DNA sequences with only short regions of homology. Since oligo mutagenesis appears to be conserved, it may play a role in remodeling the genomes of L. pneumophila and species across the Bacterial Domain.PHDMicrobiology and ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97976/1/abbryan_1.pd

Supplementary material to "Replacement of GroEL in Escherichia coli by the group II chaperonin from the archaeon Methanococcus maripaludis"

Supplementary material to "Replacement of GroEL in Escherichia coli by the group II chaperonin from the archaeon Methanococcus maripaludis