Percolation in invariant Poisson graphs with i.i.d. degrees

Let each point of a homogeneous Poisson process in R^d independently be equipped with a random number of stubs (half-edges) according to a given probability distribution mu on the positive integers. We consider translation-invariant schemes for perfectly matching the stubs to obtain a simple graph with degree distribution mu. Leaving aside degenerate cases, we prove that for any mu there exist schemes that give only finite components as well as schemes that give infinite components. For a particular matching scheme that is a natural extension of Gale-Shapley stable marriage, we give sufficient conditions on mu for the absence and presence of infinite components

Stable isotope profile (C, N, O, S) of Irish raw milk: Baseline data for authentication

Grass-based milk production is a major contributor to Irish agricultural output. The study characterized the Irish milk pool using stable isotope ratio analysis of carbon, nitrogen, oxygen and sulphur. Authentic raw milk samples were collected from 50 farms on five occasions over 13 months. Mean values of −27.11, 6.79, −3.27 and 6.16‰ were obtained for δ13C, δ15N, δ18O and δ34S, respectively. δ13C values reflected a high level of grass input and values increased with increasing cereal concentrate feed input (P < 0.001). δ18O values were most negative in spring. There was a significant interaction between feed and season for δ13C and δ15N values (P < 0.05), with the impact of concentrate feeding most evident in spring. δ34S values were lowest at the highest level of concentrate input (P < 0.05). The isotopic values reported here describe the Irish milk pool and may offer the potential to discriminate Irish milk and dairy products from similar commodities from other countries

ELF5 modulates the estrogen receptor cistrome in breast cancer.

Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

The repulsive lattice gas, the independent-set polynomial, and the Lov\'asz local lemma

We elucidate the close connection between the repulsive lattice gas in equilibrium statistical mechanics and the Lovasz local lemma in probabilistic combinatorics. We show that the conclusion of the Lovasz local lemma holds for dependency graph G and probabilities {p_x} if and only if the independent-set polynomial for G is nonvanishing in the polydisc of radii {p_x}. Furthermore, we show that the usual proof of the Lovasz local lemma -- which provides a sufficient condition for this to occur -- corresponds to a simple inductive argument for the nonvanishing of the independent-set polynomial in a polydisc, which was discovered implicitly by Shearer and explicitly by Dobrushin. We also present some refinements and extensions of both arguments, including a generalization of the Lovasz local lemma that allows for "soft" dependencies. In addition, we prove some general properties of the partition function of a repulsive lattice gas, most of which are consequences of the alternating-sign property for the Mayer coefficients. We conclude with a brief discussion of the repulsive lattice gas on countably infinite graphs.Comment: LaTex2e, 97 pages. Version 2 makes slight changes to improve clarity. To be published in J. Stat. Phy

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient\u27s ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; \u3e80% cycling protocol delivery; \u3e80% outcomes measured and \u3e80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830

COVID-19 preparedness—a survey among neonatal care providers in low- and middle-income countries

Objective - To evaluate COVID-19 pandemic preparedness, available resources, and guidelines for neonatal care delivery among neonatal health care providers in low- and middle-income countries (LMICs) across all continents. Study design - Cross-sectional, web-based survey administered between May and June, 2020. Results - Of 189 invited participants in 69 LMICs, we received 145 (77%) responses from 58 (84%) countries. The pandemic provides significant challenges to neonatal care, particularly in low-income countries. Respondents noted exacerbations of preexisting shortages in staffing, equipment, and isolation capabilities. In Sub-Saharan Africa, 9/35 (26%) respondents noted increased mortality in non-COVID-19-infected infants. Clinical practices on cord clamping, isolation, and breastfeeding varied widely, often not in line with World Health Organization guidelines. Most respondents noted family access restrictions, and limited shared decision-making. Conclusions - Many LMICs face an exacerbation of preexisting resource challenges for neonatal care during the pandemic. Variable approaches to care delivery and deviations from guidelines provide opportunities for international collaborative improvement

An Inserted α/β Subdomain Shapes the Catalytic Pocket of Lactobacillus johnsonii Cinnamoyl Esterase

Microbial enzymes produced in the gastrointestinal tract are primarily responsible for the release and biochemical transformation of absorbable bioactive monophenols. In the present work we described the crystal structure of LJ0536, a serine cinnamoyl esterase produced by the probiotic bacterium Lactobacillus johnsonii N6.2.We crystallized LJ0536 in the apo form and in three substrate-bound complexes. The structure showed a canonical α/β fold characteristic of esterases, and the enzyme is dimeric. Two classical serine esterase motifs (GlyXSerXGly) can be recognized from the amino acid sequence, and the structure revealed that the catalytic triad of the enzyme is formed by Ser(106), His(225), and Asp(197), while the other motif is non-functional. In all substrate-bound complexes, the aromatic acyl group of the ester compound was bound in the deepest part of the catalytic pocket. The binding pocket also contained an unoccupied area that could accommodate larger ligands. The structure revealed a prominent inserted α/β subdomain of 54 amino acids, from which multiple contacts to the aromatic acyl groups of the substrates are made. Inserts of this size are seen in other esterases, but the secondary structure topology of this subdomain of LJ0536 is unique to this enzyme and its closest homolog (Est1E) in the Protein Databank.The binding mechanism characterized (involving the inserted α/β subdomain) clearly differentiates LJ0536 from enzymes with similar activity of a fungal origin. The structural features herein described together with the activity profile of LJ0536 suggest that this enzyme should be clustered in a new group of bacterial cinnamoyl esterases