Structure and enumeration of (3+1)-free posets

A poset is (3+1)-free if it does not contain the disjoint union of chains of length 3 and 1 as an induced subposet. These posets play a central role in the (3+1)-free conjecture of Stanley and Stembridge. Lewis and Zhang have enumerated (3+1)-free posets in the graded case by decomposing them into bipartite graphs, but until now the general enumeration problem has remained open. We give a finer decomposition into bipartite graphs which applies to all (3+1)-free posets and obtain generating functions which count (3+1)-free posets with labelled or unlabelled vertices. Using this decomposition, we obtain a decomposition of the automorphism group and asymptotics for the number of (3+1)-free posets.Comment: 28 pages, 5 figures. New version includes substantial changes to clarify the construction of skeleta and the enumeration. An extended abstract of this paper appears as arXiv:1212.535

Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia : a randomized controlled trial

Context: Cognitive behavioral therapy (CBT) and hypnotic medications are efficacious for short-term treatment of insomnia, but few patients achieve complete remission with any single treatment. It is unclear whether combined or maintenance therapies would enhance outcome. Objectives: To evaluate the added value of medication over CBT alone for acute treatment of insomnia and the effects of maintenance therapies on long-term outcome. Design, Setting, and Patients: Prospective, randomized controlled trial involving 2-stage therapy for 160 adults with persistent insomnia treated at a university hospital sleep center in Canada between January 2002 and April 2005. Interventions: Participants received CBT alone or CBT plus 10 mg/d (taken at bedtime) ofzolpidemforaninitial6-weektherapy,followedbyextended6-monththerapy.Patients initially treated with CBT attended monthly maintenance CBT for 6 months or received no additional treatment and those initially treated with combined therapy (CBT plus 10 mg/d of zolpidem) continued with CBT plus intermittent use of zolpidem or CBT only. Main Outcome Measures: Sleep onset latency, time awake after sleep onset, total sleep time, and sleep efficiency derived from daily diaries (primary outcomes); treatment response and remission rates derived from the Insomnia Severity Index (secondary outcomes). Results: Cognitive behavioral therapy used singly or in combination with zolpidem produced significant improvements in sleep latency, time awake after sleep onset, and sleep efficiency during initial therapy (all P .001); a larger increase of sleep time was obtained with the combined approach (P=.04). Both CBT alone and CBT plus zolpidem produced similar rates of treatment responders (60% [45/75] vs 61% [45/74], respectively; P=.84) and treatment remissions (39% [29/75] vs 44% [33/74], respectively; P=.52) with the 6-week acute treatment, but combined therapy produced a higher remission rate compared with CBT alone during the 6-month extended therapy phase and the 6-month follow-up period (56% [43/74 and 32/59] vs 43% [34/75 and 28/68]; P=.05). The best long-term outcome was obtained with patients treated with combined therapy initially, followed by CBT alone, as evidenced by higher remission rates at the 6-month follow-up compared with patients who continued to take zolpidem during extended therapy (68% [20/30] vs 42% [12/29]; P=.04). Conclusion: In patients with persistent insomnia, the addition of medication to CBT produced added benefits during acute therapy, but long-term outcome was optimized when medication is discontinued during maintenance CBT

NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas.</p> <p>Results</p> <p>We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines). Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells.</p> <p>Conclusion</p> <p>These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.</p

Structure and enumeration of (3+1)(3+1)-free posets (extended abstract)

A poset is $(3+1)$-free if it does not contain the disjoint union of chains of length 3 and 1 as an induced subposet. These posets are the subject of the $(3+1)$-free conjecture of Stanley and Stembridge. Recently, Lewis and Zhang have enumerated $\textit{graded}$ $(3+1)$-free posets, but until now the general enumeration problem has remained open. We enumerate all $(3+1)$-free posets by giving a decomposition into bipartite graphs, and obtain generating functions for $(3+1)$-free posets with labelled or unlabelled vertices

DOP17 Identification of biomarkers and mechanistic insight for upadacitinib in ulcerative colitis: Analysis of serum inflammatory mediators in the phase 2b U-ACHIEVE study

Abstract Background The U-ACHIEVE trial evaluated upadacitinib (UPA), an oral JAK1 selective inhibitor, in patients with moderately to severely active ulcerative colitis (UC). Patient-reported and endoscopic outcomes improved after UPA treatment. This analysis used pharmacodynamic profiling to link changes in serum biomarkers to changes in UC disease activity, and to assess the UPA mechanism of action in UC. Methods U-ACHIEVE (NCT02819635) was a randomised, double-blind, placebo (PBO)-controlled phase 2b clinical trial. Adults with an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies were randomised to receive 7.5, 15, 30, or 45 mg UPA once daily or PBO for 8 weeks (weeks). Serum samples (baseline [BL], weeks 2, 4, and 8) were analysed by OLINK® inflammation panel (92 proteins) and by Singulex immunoassay for interleukin-1b (IL-1b), IL-17A, IL-17F, and IL-22. Protein-level changes were analysed by a mixed-effect model; BL protein level was adjusted as a covariate; treatment group, time point, and their interaction were included as fixed effects. Spearman rank-correlation coefficients were used to determine the relationship between changes of serum biomarker levels and improvements in adapted Mayo scores and endoscopic subscores. Multiplicity adjusted P values were calculated using 1000 runs of random permutations. Results Paired BL and week 8 serum samples were available from 114 patients (PBO, n = 17; UPA 7.5 mg, n = 21; UPA 15 mg, n = 21; UPA 30 mg, n = 29; UPA 45 mg, n = 26). UPA treatment reduced expression of pro-inflammatory mediators associated with immune cell migration, type I/II IFN responses, T-cell responses, macrophage and dendritic cell activity and increased expression of biomarkers associated with haematopoiesis, neuroprotection and mucosal repair in a dose-dependent manner. Improvements in adapted Mayo score, endoscopic subscore, and stool frequency correlated with increases in CX3CL1, DNER and FLt3L (p &lt; 0.05 for all). Endoscopic improvements correlated with reductions in OSM, and improvements in fatigue correlated with increases in CCL25 and NT-3. There was a substantial overlap in biomarkers modulated by UPA in patients with UC and Crohn's disease (Figure). Conclusion UPA modulated expression of serum pro-inflammatory mediators found in pathways associated with the pathogenesis of UC, including immune cell migration, type I/II IFN responses, T-cell responses, macrophage and dendritic cell activity, haematopoiesis, neuroprotection, and mucosal repair. Consistent correlations were observed between changes in biomarker expression and improvements in disease activity and symptoms of UC

Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)

BACKGROUND: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect. METHODS: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population. RESULTS: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe. CONCLUSION: The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans

Conjugation-Length Dependence of Spin-Dependent Exciton Formation Rates in Pi-Conjugated Oligomers and Polymers

We have measured the ratio, r = $\sigma_S/\sigma_T$ of the formation cross section, $\sigma$ of singlet ($\sigma_S$) and triplet ($\sigma_T$) excitons from oppositely charged polarons in a large variety of $\pi$-conjugated oligomer and polymer films, using the photoinduced absorption and optically detected magnetic resonance spectroscopies. The ratio r is directly related to the singlet exciton yield, which in turn determines the maximum electroluminescence quantum efficiency in organic light emitting diodes (OLED). We discovered that r increases with the conjugation length, CL; in fact a universal dependence exists in which $r^{-1}$ depends linearly on $CL^{-1}$, irrespective of the chain backbone structure. These results indicate that $\pi$-conjugated polymers have a clear advantage over small molecules in OLED applications.Comment: 5 pages, 4 figure

Twisted Yangians for symmetric pairs of types B, C, D

We study a class of quantized enveloping algebras, called twisted Yangians, associated with the symmetric pairs of types B, C, D in Cartan's classification. These algebras can be regarded as coideal subalgebras of the extended Yangian for orthogonal or symplectic Lie algebras. They can also be presented as quotients of a reflection algebra by additional symmetry relations. We prove an analogue of the Poincare-Birkoff-Witt Theorem, determine their centres and study also extended reflection algebras