Coverings of graded pointed Hopf algebras

We introduce the concept of a covering of a graded pointed Hopf algebra. The theory developed shows that coverings of a bosonized Nichols algebra can be concretely expressed by biproducts using a quotient of the universal coalgebra covering group of the Nichols algebra. If there are enough quadratic relations, the universal coalgebra covering is given by the bosonization by the enveloping group of the underlying rack.Comment: to appear in J. of Algebr

The osteogenic effect of mineral trioxide aggregate and modified-mineral trioxide aggregate on normal human osteoblast cells

Thesis (MSD) -- Boston University Goldman School of Dental Medicine, 2006 (Endodontics).Includes bibliography: leaves 89-96.Mineral Trioxide Aggregate (MTA), a relatively new material, has been widely used for root-end fillings, Pulp capping, perforation repairs and other endodontic procedures. Many studies have reported the biocompatibiIity of MTA in vitro and in vivo. Previous studies have shown that MTA provides a biologically active substrate for bone cells, stimulates interleukin production, and that osteoblasts have a favorable response to MTA as compared with IRM and amalgam (Koh et al. 1998; Zhu et al., 2000). In this in vitro study a modification was made to conventional MTA (modified MTA), with the addition of Silicon (Si). The effects of MTA and modified-MTA, on cell attachment efficiency, cell proliferation rate, alkaline phosphatase activity and osteocalcin expression were compared. Human osteoblast-like cells derived from healthy alveolar bone explants were used and grown to second passage in order to perform these experiments. Human osteoblast-like cells were grown and cultured in 24 well plates, in the presence of MTA, modified-MTA and control (plastic culture dish, PCD). Cells were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with F-12 nutrient mixture, fetal bovine serum (FBS), Penicillin G (5000 U/ml)/streptomycin sulphate (5000 [mu]g/ml), and 250 [mu]g/ml Amphotericin B. Cells were cultured for periods of 12 and 20 days. MTA and modified-MTA were mixed according to manufacturer’s instructions and made into 15.5 mm in diameter, 1.5 mm thickness discs and allowed to set for a period of 24 hours at 37[degrees]C, 5%CO[2], and 1OO% humidity. Before the 12th and 2Oth day, differentiation medium containing vitamin D3 was added to the cell cultures, a period of 48 hours before the day the experiment was conducted. Observation of pH was made throughout the duration of the culture. Cell attachment and proliferation rate were determined by measuring the optical density of crystal violet dye in fixed culture cells. Alkaline phosphatase activity was determined by measuring the optical density of released p-Nitrophenol from a fixed cellular layer. Osteocalcin expression was determined by measuring I[125]-labeled antibody in extracted culture media. All data was normalized on per 10[4]or 10[5] cells basis. One-way analysis of variance (ANOVA) and a two sample t-test assuming equal or non-equal variance were used for statistical analysis on the data. The mean pH of the culture medium cultured in the presence of MTA, modified-MTA, and control decreased over 18 days of culture with a slight increase around 20 days.　There was no significant difference between osteoblast cells grown in the presence of MTA, modified-MTA, and control regarding cell attachment efficiency at 16 hours. At 12 and 20 days, attachment and proliferation rate was significantly higher with the MTA and modified-MTA groups, bu there was no significant difference between them. At 12 and 20 days, the control group of osteoblast cells had higher ALP activity than the MTA and modified-MTA group. At 20 days, MTA and modified-MTA expressed higher amounts of osteocalcin than the control group. Based on the results of this in vitro study, MTA and modified-MTA are both capable of stimulating osteogenic effects in normal human osteoblast cultures. This study demonstrated the role of silicon in stimulating osteogenesis of normal human osteoblast cells. Further studies need to be conducted in order to evaluate better modifications of conventional MTA in order to evaluate the favorable response from human osteoblast cells in contact with the material

Age-Specific Associations of Usual Blood Pressure Variability With Cardiovascular Disease and Mortality: 10-Year Diabetes Mellitus Cohort Study.

Background The detrimental effects of increased variability in systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality risk in patients with diabetes mellitus remains unclear. This study evaluated age-specific association of usual SBP visit-to-visit variability with CVD and mortality in patients with type 2 diabetes mellitus. Methods and Results A retrospective cohort study investigated 155 982 patients with diabetes mellitus aged 45 to 84 years without CVD at baseline (2008-2010). Usual SBP variability was estimated using SBP SD obtained from a mixed-effects model. Age-specific associations (45-54, 55-64, 65-74, 75-84 years) between usual SBP variability, CVD, and mortality risk were assessed by Cox regression adjusted for patient characteristics. After a median follow-up of 9.7 years, 49 816 events (including 34 039 CVD events and 29 211 mortalities) were identified. Elevated SBP variability was independently, positively, and log-linearly associated with higher CVD and mortality risk among all age groups, with no evidence of any threshold effects. The excess CVD and mortality risk per 5 mm Hg increase in SBP variability within the 45 to 54 age group is >3 times higher than the 70 to 79 age group (hazard ratio, 1.66; 95% CI, 1.49-1.85 versus hazard ratio, 1.19; 95% CI, 1.15-1.23). The significant associations remained consistent among all subgroups. Patients with younger age had a higher association of SBP variability with event outcomes. Conclusions The findings suggest that SBP visit-to-visit variability was strongly associated with CVD and mortality with no evidence of a threshold effect in a population with diabetes mellitus. As well as controlling overall blood pressure levels, SBP visit-to-visit variability should be monitored and evaluated in routine practice, in particular for younger patients

Convex Hull of Points Lying on Lines in o(n log n) Time after Preprocessing

Motivated by the desire to cope with data imprecision, we study methods for taking advantage of preliminary information about point sets in order to speed up the computation of certain structures associated with them. In particular, we study the following problem: given a set L of n lines in the plane, we wish to preprocess L such that later, upon receiving a set P of n points, each of which lies on a distinct line of L, we can construct the convex hull of P efficiently. We show that in quadratic time and space it is possible to construct a data structure on L that enables us to compute the convex hull of any such point set P in O(n alpha(n) log* n) expected time. If we further assume that the points are "oblivious" with respect to the data structure, the running time improves to O(n alpha(n)). The analysis applies almost verbatim when L is a set of line-segments, and yields similar asymptotic bounds. We present several extensions, including a trade-off between space and query time and an output-sensitive algorithm. We also study the "dual problem" where we show how to efficiently compute the (<= k)-level of n lines in the plane, each of which lies on a distinct point (given in advance). We complement our results by Omega(n log n) lower bounds under the algebraic computation tree model for several related problems, including sorting a set of points (according to, say, their x-order), each of which lies on a given line known in advance. Therefore, the convex hull problem under our setting is easier than sorting, contrary to the "standard" convex hull and sorting problems, in which the two problems require Theta(n log n) steps in the worst case (under the algebraic computation tree model).Comment: 26 pages, 5 figures, 1 appendix; a preliminary version appeared at SoCG 201

Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell–cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations

Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment

Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells in the bone marrow (BM). MM remains an incurable disease, with the majority of patients experiencing multiple relapses from different drugs. The MM tumor microenvironment (TME) and in particular bone-marrow stromal cells (BMSCs) play a crucial role in the development of drug resistance. Metabolic reprogramming is emerging as a hallmark of cancer that can potentially be exploited for cancer treatment. Recent studies show that metabolism is further adjusted in MM cells during the development of drug resistance. However, little is known about the role of BMSCs in inducing metabolic changes that are associated with drug resistance. In this Perspective, we summarize current knowledge concerning the metabolic reprogramming of MM, with a focus on those changes associated with drug resistance to the proteasome inhibitor Bortezomib (BTZ). In addition, we present proof-of-concept fluxomics (glucose isotope-tracing) and Seahorse data to show that co-culture of MM cells with BMSCs skews the metabolic phenotype of MM cells towards a drug-resistant phenotype, with increased oxidative phosphorylation (OXPHOS), serine synthesis pathway (SSP), TCA cycle and glutathione (GSH) synthesis. Given the crucial role of BMSCs in conveying drug resistance, insights into the metabolic interaction between MM and BMSCs may ultimately aid in the identification of novel metabolic targets that can be exploited for therapy

Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNF, sTNFRI and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality