The Effect of Planarization on Width

We study the effects of planarization (the construction of a planar diagram $D$ from a non-planar graph $G$ by replacing each crossing by a new vertex) on graph width parameters. We show that for treewidth, pathwidth, branchwidth, clique-width, and tree-depth there exists a family of $n$-vertex graphs with bounded parameter value, all of whose planarizations have parameter value $\Omega(n)$. However, for bandwidth, cutwidth, and carving width, every graph with bounded parameter value has a planarization of linear size whose parameter value remains bounded. The same is true for the treewidth, pathwidth, and branchwidth of graphs of bounded degree.Comment: 15 pages, 6 figures. To appear at the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Djelovanje različitih razrjeđivača na svojstva spermija i plodnost križanih svinja u sjevernoistočnoj Indiji.

The study was conducted to deduce the efficacy and suitability of three extenders: Beltsville thawing solution (BTS), Kiev and Modena extenders, on the preservation and fertility of boar semen. Semen ejaculates with more than 70% sperm motility from six Hampshire boars were used and preserved at 17 °C. The extended semen was evaluated for motility, viability, acrosomal and plasma membrane integrity from day 0 to 5 of preservation. There was a significant (P<0.01) reduction in sperm motility and viability between days 0 to 4, but no significant difference between day 0 and 2. BTS and Modena maintained significantly (P<0.05) higher sperm motility and viability as compared to Kiev. Plasma membrane integrity did not differ significantly up to day 2, but was significantly reduced on days 3 (P<0.05) and 4 (P<0.01). BTS and Modena extenders had significantly (P<0.05) higher plasma membrane integrity. By day 5, the percentage of mean sperm with intact acrosome was 80.4 ± 2.5, 81.2 ± 2.3 and 75.7 ± 2.7, in BTS, Modena and Kiev, respectively, with significant (P<0.05) increases in acrosomal damage after two days of storage, irrespective of all extenders. Farrowing rate and litter size did not differ significantly during the initial period of storage, but there was a significant difference after day 3 (P<0.05) in all extenders used. BTS and Modena maintained a farrowing rate of more than 60% on day 5, in contrast to 50% with the Kiev extender. The study concluded that both BTS and Modena are better extenders for short term storage of boar liquid semen as compared to the Kiev extender, and could be used efficiently in crossbreeding of pigs of north-eastern India.Istraživanje je provedeno kako bi se utvrdila učinkovitost i prikladnost beltsvilskog (BTS), kijevskog i modenskog razrjeđivača za očuvanje i plodnost nerastova sjemena. Upotrijebljeni su ejakulati sjemena od 6 hempširskih nerastova s pokretljivošću spermija većom od 70%, koji su sačuvani na 17 °C. Razrijeđeno sjeme procjenjivano je od 0. do 5. dana s obzirom na pokretljivost, živost te cjelovitost akrosomalne i plazmine membrane. Tijekom razdoblja od 0. do 4. dana došlo je do signifikantnog (P<0,01) sniženja pokretljivosti i živosti spermija, no signifikantne razlike između nultog i drugog dana nisu utvrđene. U usporedbi s kijevskim razrjeđivačem, BTS i modenski razrjeđivači su održavali signifikantno (P<0,05) višu pokretljivost i životnost spermija. Cjelovitost plazmine membrane nije se signifikantno razlikovala do 2. dana, ali je signifikantno snižena tijekom 3. dana (P<0,05) i 4. dana (P<0,01). Cjelovitost plazmine membrane bila je signifikantno veća (P<0,05) pri uporabi BTS i modenskog razrjeđivača. Do 5. dana, prosječni postotak spermija s nepromijenjenim akrosomom iznosio je kod BTS razrjeđivača 80,4 ± 2,5, kod modenskog razrjeđivača 81,2 ± 2,3, a kod kijevskog razrjeđivača 75,7 ± 2,7. Pri tome je, bez obzira na razrjeđivač, od 2. dana utvrđen signifikantni porast (P<0,05) spermija s oštećenim akrosomima. U početnom razdoblju stopa prasenja i veličina legla nisu se signifikantno razlikovale, no nakon 3. dana kod svih upotrijebljenih razrjeđivača razlike su bile signifikantne (P<0,05). Peti dan stopa prasenja kod BTS i modenskog razrjeđivača održala se preko 60% za razliku od kijevskog razrjeđivača kod kojeg je stopa prasivosti iznosila 50%. Istraživanjem se zaključuje da BTS i modenski razrjeđivači mogu, u odnosu na kijevski razrjeđivač, bolje poslužiti za kratkotrajno pohranjivanje nerastovog tekućeg sjemena, te kao takvi biti i učinkovitiji u križanjima svinja sjevernoistočne Indije

Posterior-based proposals for speeding up Markov chain Monte Carlo

Markov chain Monte Carlo (MCMC) is widely used for Bayesian inference in models of complex systems. Performance, however, is often unsatisfactory in models with many latent variables due to so-called poor mixing, necessitating development of application specific implementations. This paper introduces "posterior-based proposals" (PBPs), a new type of MCMC update applicable to a huge class of statistical models (whose conditional dependence structures are represented by directed acyclic graphs). PBPs generates large joint updates in parameter and latent variable space, whilst retaining good acceptance rates (typically 33%). Evaluation against other approaches (from standard Gibbs / random walk updates to state-of-the-art Hamiltonian and particle MCMC methods) was carried out for widely varying model types: an individual-based model for disease diagnostic test data, a financial stochastic volatility model, a mixed model used in statistical genetics and a population model used in ecology. Whilst different methods worked better or worse in different scenarios, PBPs were found to be either near to the fastest or significantly faster than the next best approach (by up to a factor of 10). PBPs therefore represent an additional general purpose technique that can be usefully applied in a wide variety of contexts.Comment: 54 pages, 11 figures, 2 table

Changes in expression of monocarboxylate transporters, heat shock proteins and meat quality of Large White Yorkshire and Ghungroo pigs during hot summer period

Objective Present study explores the effect of hot summer period on the glycolytic rate of early post-mortem meat quality of Ghungroo and Large White Yorkshire (LWY) pig and comparative adaptability to high temperature between above breeds by shifting the expression of stress related genes like mono-carboxylate transporters (MCTs) and heat shock proteins (HSPs). Methods Healthy pigs of two different breeds, viz., LYW and Ghungroo (20 from each) were maintained during hot summer period (May to June) with a mean temperature of about 38°C. The pigs were slaughtered and meat samples from the longissimus dorsi (LD) muscles were analyzed for pH, glycogen and lactate content and mRNA expression. Following 24 h of chilling, LD muscle was also taken from the carcasses to evaluate protein solubility and different meat quality measurements. Results LWY exhibited significantly (p<0.01) higher plasma cortisol and lactate dehydrogenase concentration than Ghungroo indicating their higher sensitivity to high temperature. LD muscle from LWY pigs revealed lower initial and ultimate pH values and higher drip loss compared to Ghungroo, indicating a faster rate of pH fall. LD muscle of Ghungroo had significantly lower lactate content at 45 min postmortem indicating normal postmortem glycolysis and much slower glycolytic rate at early postmortem. LD muscle of LWY showed rapid postmortem glycolysis, higher drip loss and higher degrees of protein denaturation. Ghungroo exhibited slightly better water holding capacity, lower cooking loss and higher protein solubility. All HSPs (HSP27, HSP70, and HSP90) and MCTs (MCT1, MCT2, and MCT4) in the LD muscle of pigs inclined to increase more in Ghungroo than LWY when exposed to high temperature. Conclusion Effect of high temperature on the variation of HSPs and MCTs may play a crucial role in thermal tolerance and adaptation to different climatic conditions, pH regulation, muscle acidification, drip loss, protein denaturation and also in postmortem meat quality development

Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer

The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5′-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion ‘rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival

Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-κB-dependent Genes

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase-dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-κB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-κB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-κB activation and chromatin modifications, which have implications in pathogenesis of COPD

DNA methylation in glioblastoma: impact on gene expression and clinical outcome

International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions

Enterobactin-Mediated Delivery of β-Lactam Antibiotics Enhances Antibacterial Activity against Pathogenic Escherichia coli

The design, synthesis, and characterization of enterobactin–antibiotic conjugates, hereafter Ent-Amp/Amx, where the β-lactam antibiotics ampicillin (Amp) and amoxicillin (Amx) are linked to a monofunctionalized enterobactin scaffold via a stable poly(ethylene glycol) linker are reported. Under conditions of iron limitation, these siderophore-modified antibiotics provide enhanced antibacterial activity against Escherichia coli strains, including uropathogenic E. coli CFT073 and UTI89, enterohemorrhagic E. coli O157:H7, and enterotoxigenic E. coli O78:H11, compared to the parent β-lactams. Studies with E. coli K-12 derivatives defective in ferric enterobactin transport reveal that the enhanced antibacterial activity observed for this strain requires the outer membrane ferric enterobactin transporter FepA. A remarkable 1000-fold decrease in minimum inhibitory concentration (MIC) value is observed for uropathogenic E. coli CFT073 relative to Amp/Amx, and time-kill kinetic studies demonstrate that Ent-Amp/Amx kill this strain more rapidly at 10-fold lower concentrations than the parent antibiotics. Moreover, Ent-Amp and Ent-Amx selectively kill E. coli CFT073 co-cultured with other bacterial species such as Staphylococcus aureus, and Ent-Amp exhibits low cytotoxicity against human T84 intestinal cells in both the apo and iron-bound forms. These studies demonstrate that the native enterobactin platform provides a means to effectively deliver antibacterial cargo across the outer membrane permeability barrier of Gram-negative pathogens utilizing enterobactin for iron acquisition.Pacific Southwest Regional Center of Excellence for Biodefense and Emerging Infectious DiseaseKinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

Effects of Cyclic Strain and Growth Factors on Vascular Smooth Muscle Cell Responses

Under physiological and pathological conditions, vascular smooth muscle cells (SMC) are exposed to different biochemical factors and biomechanical forces. Previous studies pertaining to SMC responses have not investigated the effects of both factors on SMCs. Thus, in our research we investigated the combined effects of growth factors like Bfgf (basic fibroblast growth factor), TGF-β (transforming growth factor β) and PDGF (platelet-derived growth factor) along with physiological cyclic strain on SMC responses. Physiological cyclic strain (10% strain) significantly reduced SMC proliferation compared to static controls while addition of growth factors bFGF, TGF-β or PDGF-AB had a positive influence on SMC growth compared to strain alone. Microarray analysis of SMCs exposed to these growth factors and cyclic strain showed that several bioactive genes (vascular endothelial growth factor, epidermal growth factor receptor, etc.) were altered upon exposure. Further work involving biochemical and pathological cyclic strain stimulation will help us better understand the role of cyclic strain and growth factors in vascular functions and development of vascular disorders