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

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

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

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

Visualising single molecules of HIV-1 and miRNA nucleic acids

BackgroundThe scarcity of certain nucleic acid species and the small size of target sequences such as miRNA, impose a significant barrier to subcellular visualization and present a major challenge to cell biologists. Here, we offer a generic and highly sensitive visualization approach (oligo fluorescent in situ hybridization, O-FISH) that can be used to detect such nucleic acids using a single-oligonucleotide probe of 19–26 nucleotides in length.ResultsWe used O-FISH to visualize miR146a in human and avian cells. Furthermore, we reveal the sensitivity of O-FISH detection by using a HIV-1 model system to show that as little as 1–2 copies of nucleic acids can be detected in a single cell. We were able to discern newly synthesized viral cDNA and, moreover, observed that certain HIV RNA sequences are only transiently available for O-FISH detection.ConclusionsTaken together, these results suggest that the O-FISH method can potentially be used for in situ probing of, as few as, 1–2 copies of nucleic acid and, additionally, to visualize small RNA such as miRNA. We further propose that the O-FISH method could be extended to understand viral function by probing newly transcribed viral intermediates; and discern the localisation of nucleic acids of interest. Additionally, interrogating the conformation and structure of a particular nucleic acid in situ might also be possible, based on the accessibility of a target sequence

A spatial interaction model of Qin-Han Dynasty organisation on the northern frontier and the location of the Zhidao highway (China)

Modelling pathways or traffic flows on the basis of only partially-preserved or recovered evidence is of considerable interest to archaeologists. This study uses spatial interaction modelling to investigate the well-known Zhidao (直道) highway that was a major military road to the northern frontier in the Qin-Han Dynasty. The model simulates hypothetical flows among a set of known forts on China's north-western frontier and then compares the results to more and less certain attestations of the route of the Zhidao highway from archaeological and documentary evidence. We are able to reveal: (a) that logistical connectivity was unsurprisingly a priority along the Qin-Han frontier and (b) that the contemporary combination of forts and major east–west defensive walls were integrated via the location of the Zhidao highway. The approach presented here is reproducible via accompanying code and data, and could be transferred to a range of other archaeological applications where military installations, linear defensive works and highways interact in potentially complex and interesting ways

Effect of postactivation potentiation on fifty-meter freestyle in national swimmers

Effect of postactivation potentiation (PAP) on fifty meters freestyle in national swimmers. 2013.- The purpose of this study was to examine the effect of PAP on 50m freestyle in national-level swimmers. Four warm-ups were compared: A traditional race-specific warm-up (RSWU), upper body PAP (UBPAP), lower body PAP (LBPAP) and combined PAP warm-up (CPAP). Eighteen (10 men, 8 women) national-level swimmers participated in this study, which included seven separate testing sessions. Participants' 3 repetition maximum (3RM) of the pull-up (PU) was established in session 1. In session 2, rest periods for muscle enhancement of the upper body were determined using a medicine-ballthrow test 4, 8 and 12 minutes post UBPAP stimulus (1 x 3RM of the PU). In session 3, swimmers performed a counter movement jump 4, 8 and 12 minutes post LBPAP stimulus (1x5 jumps to a box whilst carrying 10% of the participants' body weight). The 50m freestyle tests were performed on sessions 4 to 7, preceded by each warm-up protocol and corresponding rest periods. A repeated measures ANOVA (p<0.05) and Bonferroni post hoc test revealed that RSWU elicited faster swimming times than UBPAP (29.00 ± 2.05 vs. 29.36 ± 1.88s p=0.046). Additionally, when data were split into gender, in the male group the UBPAP elicited significantly slower times than RSWU (27.51 ± 1.06 vs. 28.01 ± 1.17s p=0.047) and CPAP (27.49 ± 1.12 vs. 28.01 ± 1.17s p=0.02). These findings suggest individualized PAP warm-up may be a valuable tool to enhance performance in sprint events, particularly in male swimmers. However, the PU may not be an appropriate PAP stimulus on its own

Observationally constrained surface mass balance of Larsen C IceShelf, Antarctica

Abstract. Combining several geophysical techniques, we reconstruct spatial and temporal patterns of surface mass balance (SMB) over Larsen C Ice Shelf (LCIS), Antarctic Peninsula. Continuous time series of snow height at five locations allow for multi-year estimates of seasonal and annual SMB over LCIS. There is high interannual variability, with an SMB of 395 ± 61 to 413 ± 42 mm w.e. y−1 in the north and a larger SMB of up to 496 ± 50 mm w.e. y−1 farther south. This difference between north and south is corroborated by winter snow accumulation derived from an airborne radar survey from 2009, which showed an average snow thickness of 0.95 m north of 76° S, and 1.12 m south of 78°. Analysis of ground-penetrating radar from several field campaigns allows for a longer-term perspective of spatial SMB: a particularly strong and coherent reflection horizon below 25–44 m w.e. of ice and firn is observed in radargrams collected across the shelf. We propose that this horizon was formed in a single melt season over the ice shelf. Combining ground and airborne radar with SMB output from a regional climate model confirms that SMB increases from north to south, overprinted by a gradient of increasing SMB to the west. Previous observations show a strong decrease in firn air content toward the west, which we attribute to spatial patterns of melt, refreezing, and densification, rather than SMB. </jats:p

Silent progression in disease activity-free relapsing multiple sclerosis.

ObjectiveRates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.MethodsDisability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates.ResultsRelapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p &lt; 0.05).InterpretationLong-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666