Pseudocommutativity and Lax Idempotency for Relative Pseudomonads

We extend the classical work of Kock on strong and commutative monads, as well as the work of Hyland and Power for 2-monads, in order to define strong and pseudocommutative relative pseudomonads. In order to achieve this, we work in the more general setting of 2-multicategories rather than monoidal 2-categories. We prove analogous implications to the classical work: that a strong relative pseudomonad is a pseudo-multifunctor, and that a pseudocommutative relative pseudomonad is a multicategorical pseudomonad. Furthermore, we extend the work of L\'opez Franco with a proof that a lax-idempotent strong relative pseudomonad is pseudocommutative. We apply the results of this paper to the example of the presheaf relative pseudomonad.Comment: 28 page

Isolation and characterization of high persistence mutants of Salmonella enterica serotype Typhimurium

A small fraction of bacterial populations consist of persistent cells that are phenotypically distinct from the majority of cells by their ability to avoid killing by a variety of antimicrobial challenges. Persistence is distinct from resistance in that persistent cells are unable to grow in the presence of the antimicrobial agent or treatment, but resume growth after the selection has been removed. Presently, little is known about the genetic or physiological basis of persistence. In this study we demonstrate that Salmonella enterica serovar Typhimurium (S. typhimurium) displays the persistence phenotype. To better understand persistence in this important food-borne pathogen, we have isolated 6 mutants that show an increased ability to survive exposure to a variety of antibiotics without an increase in MIC values. All of the mutants isolated were found to have an extended lag phase, but had wild type growth rates in exponential phase. Characterization of the mutants indicates that multiple loci appear to contribute to persistence. Mapping the genes for the high persistence phenotype will reveal new insights into this widely observed phenomenon

The Poincaré series of every finitely generated module over a codimension four almost complete intersection is a rational function

AbstractLet (R, M, k) be a regular local ring in which two is a unit and let A = R/J, where J is a five generated grade four perfect ideal in R. We prove that the Poincaré series PMA(z) = Σ∞i=0 dimk TorAi(M, k)zi is a rational function for all finitely generated A-modules M. We also prove that the Eisenbud conjecture holds for A, that is, if M is an A-module whose Betti numbers are bounded, then the minimal resolution of M by free A-modules is eventually periodic of period at most two

2015 AFRL University Design Challenge

The University of Akron’s Air Force Research Laboratory’s Design Challenge Team has engineered a Heat Stress Prevention Kit that includes a facial mask in which the soldier will cool down from the inside out by breathing in the cool air circulating throughout the mask. This cool air is produced from a thermoelectric chip, which has a specific temperature difference on either side, one hot and one cold. Each of the sides is isolated from one another and with the combination of heat sinks, fans, and the simple process of breathing, a system is created by inhaling cool air. The entire system is powered and controlled by a power source including two LiPo batteries, an Arduino Uno Circuit Board, and a relay all encased in an external pouch which can attach to any Molle strap system. A bonus feature to this mask system is it can be turned into a Hypothermia Prevention Kit by switching the wires or the voltage of the thermoelectric chip

2015 AFRL University and Service Academy Design Challenge

The University of Akron’s Air Force Research Laboratory’s Design Challenge Team has engineered a Heat Stress Prevention Kit that includes a facial mask in which the soldier will cool down from the inside out by breathing in the cool air circulating throughout the mask. This cool air is produced from a thermoelectric chip, which has a specific temperature difference on either side, one hot and one cold. Each of the sides are isolated from one another and with the combination of heatsinks, fans, and the simple process of breathing, a system is created by inhaling cool air. The entire system is powered and controlled by a power source including two LiPo batteries, an Arduino Uno Circuit Board, and a relay all encased in an external pouch which can attach to any Molle strap system. A bonus feature to this mask system is it ca

Towards understanding the myometrial physiome: approaches for the construction of a virtual physiological uterus

Premature labour (PTL) is the single most significant factor contributing to neonatal morbidity in Europe with enormous attendant healthcare and social costs. Consequently, it remains a major challenge to alleviate the cause and impact of this condition. Our ability to improve the diagnosis and treatment of women most at risk of PTL is, however, actually hampered by an incomplete understanding of the ways in which the functions of the uterine myocyte are integrated to effect an appropriate biological response at the multicellular whole organ system. The level of organization required to co-ordinate labouring uterine contractile effort in time and space can be considered immense. There is a multitude of what might be considered mini-systems involved, each with their own regulatory feedback cycles, yet they each, in turn, will influence the behaviour of a related system. These include, but are not exclusive to, gestational-dependent regulation of transcription, translation, post-translational modifications, intracellular signaling dynamics, cell morphology, intercellular communication and tissue level morphology. We propose that in order to comprehend how these mini-systems integrate to facilitate uterine contraction during labour (preterm or term) we must, in concert with biological experimentation, construct detailed mathematical descriptions of our findings. This serves three purposes: firstly, providing a quantitative description of series of complex observations; secondly, proferring a database platform that informs further testable experimentation; thirdly, advancing towards the establishment of a virtual physiological uterus and in silico clinical diagnosis and treatment of PTL

Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians

Proceedings of the third international molecular pathological epidemiology (MPE) meeting

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields

Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location

Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; P het =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; P het =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors

Association Between Smoking and Molecular Subtypes of Colorectal Cancer

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P-trend <.001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P-difference = 2.1 x 10(-6)). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P-difference <.001). Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway