Powers in a class of A-strict standard episturmian words

This paper concerns a specific class of strict standard episturmian words whose directive words resemble those of characteristic Sturmian words. In particular, we explicitly determine all integer powers occurring in such infinite words, extending recent results of Damanik and Lenz (2003), who studied powers in Sturmian words. The key tools in our analysis are canonical decompositions and a generalization of singular words, which were originally defined for the ubiquitous Fibonacci word. Our main results are demonstrated via some examples, including the $k$-bonacci word: a generalization of the Fibonacci word to a $k$-letter alphabet ($k\geq2$).Comment: 26 pages; extended version of a paper presented at the 5th International Conference on Words, Montreal, Canada, September 13-17, 200

Occurrences of palindromes in characteristic Sturmian words

This paper is concerned with palindromes occurring in characteristic Sturmian words $c_\alpha$ of slope $\alpha$, where $\alpha \in (0,1)$ is an irrational. As $c_\alpha$ is a uniformly recurrent infinite word, any (palindromic) factor of $c_\alpha$ occurs infinitely many times in $c_\alpha$ with bounded gaps. Our aim is to completely describe where palindromes occur in $c_\alpha$. In particular, given any palindromic factor $u$ of $c_\alpha$, we shall establish a decomposition of $c_\alpha$ with respect to the occurrences of $u$. Such a decomposition shows precisely where $u$ occurs in $c_\alpha$, and this is directly related to the continued fraction expansion of $\alpha$.Comment: 17 page

Genome-Wide Profiling of H3K56 Acetylation and Transcription Factor Binding Sites in Human Adipocytes

The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation.Singapore. Agency for Science, Technology and Research (National Science Scholarship )Massachusetts Institute of Technology (Eugene Bell Career Development Chair)National Science Foundation (U.S.) (Award No. DBI-0821391)Pfizer Inc

Episturmian words: a survey

In this paper, we survey the rich theory of infinite episturmian words which generalize to any finite alphabet, in a rather resembling way, the well-known family of Sturmian words on two letters. After recalling definitions and basic properties, we consider episturmian morphisms that allow for a deeper study of these words. Some properties of factors are described, including factor complexity, palindromes, fractional powers, frequencies, and return words. We also consider lexicographical properties of episturmian words, as well as their connection to the balance property, and related notions such as finite episturmian words, Arnoux-Rauzy sequences, and "episkew words" that generalize the skew words of Morse and Hedlund.Comment: 36 pages; major revision: improvements + new material + more reference

Metabolites of milk intake: a metabolomic approach in UK twins with findings replicated in two European cohorts

Purpose: Milk provides a significant source of calcium, protein, vitamins and other minerals to Western populations throughout life. Due to its widespread use, the metabolic and health impact of milk consumption warrants further investigation and biomarkers would aid epidemiological studies.  Methods: Milk intake assessed by a validated food frequency questionnaire was analyzed against fasting blood metabolomic profiles from two metabolomic platforms in females from the TwinsUK cohort (n = 3559). The top metabolites were then replicated in two independent populations (EGCUT, n = 1109 and KORA, n = 1593), and the results from all cohorts were meta-analyzed.  Results: Four metabolites were significantly associated with milk intake in the TwinsUK cohort after adjustment for multiple testing (P < 8.08 × 10−5) and covariates (BMI, age, batch effects, family relatedness and dietary covariates) and replicated in the independent cohorts. Among the metabolites identified, the carnitine metabolite trimethyl-N-aminovalerate (β = 0.012, SE = 0.002, P = 2.98 × 10−12) and the nucleotide uridine (β = 0.004, SE = 0.001, P = 9.86 × 10−6) were the strongest novel predictive biomarkers from the non-targeted platform. Notably, the association between trimethyl-N-aminovalerate and milk intake was significant in a group of MZ twins discordant for milk intake (β = 0.050, SE = 0.015, P = 7.53 × 10−4) and validated in the urine of 236 UK twins (β = 0.091, SE = 0.032, P = 0.004). Two metabolites from the targeted platform, hydroxysphingomyelin C14:1 (β = 0.034, SE = 0.005, P = 9.75 × 10−14) and diacylphosphatidylcholine C28:1 (β = 0.034, SE = 0.004, P = 4.53 × 10−16), were also replicated.  Conclusions: We identified and replicated in independent populations four novel biomarkers of milk intake: trimethyl-N-aminovalerate, uridine, hydroxysphingomyelin C14:1 and diacylphosphatidylcholine C28:1. Together, these metabolites have potential to objectively examine and refine milk-disease associations

Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans

BACKGROUND: HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors. METHODOLOGY/PRINCIPAL FINDINGS: Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)]. CONCLUSIONS/SIGNIFICANCE: HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI

Conjugates of characteristic Sturmian words generated by morphisms

This article is concerned with characteristic Sturmian words of slope α and 1-α (denoted by cα and c1-α resp.), where α∈(0,1) is an irrational number such that α=[0;1+d1,d2,..., dn] with dn≥d1≥1. It is known that both cα and c1-α are fixed points of non-trivial (standard) morphisms σ and σ̂, respectively, if and only if α has a continued fraction expansion as above. Accordingly, such words cα and c1-α are generated by the respective morphisms σ and σ̂. For the particular case when α=[0;2,r̄] (r≥1), we give a decomposition of each conjugate of cα (and hence c1-α) into generalized adjoining singular words, by considering conjugates of powers of the standard morphism σ by which it is generated. This extends a recent result of Levé and Séébold on conjugates of the infinite Fibonacci word

Willingness to trade-off: An intermediate factor in patient decision-making regarding escalating care

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants ( n  = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making