440 research outputs found
Not every pseudoalgebra is equivalent to a strict one
We describe a finitary 2-monad on a locally finitely presentable 2-category
for which not every pseudoalgebra is equivalent to a strict one. This shows
that having rank is not a sufficient condition on a 2-monad for every
pseudoalgebra to be strictifiable. Our counterexample comes from higher
category theory: the strict algebras are strict 3-categories, and the
pseudoalgebras are a type of semi-strict 3-category lying in between
Gray-categories and tricategories. Thus, the result follows from the fact that
not every Gray-category is equivalent to a strict 3-category, connecting
2-categorical and higher-categorical coherence theory. In particular, any
nontrivially braided monoidal category gives an example of a pseudoalgebra that
is not equivalent to a strict one.Comment: 17 pages; added more explanation; final version, to appear in Adv.
Mat
A unified framework for generalized multicategories
Notions of generalized multicategory have been defined in numerous contexts
throughout the literature, and include such diverse examples as symmetric
multicategories, globular operads, Lawvere theories, and topological spaces. In
each case, generalized multicategories are defined as the "lax algebras" or
"Kleisli monoids" relative to a "monad" on a bicategory. However, the meanings
of these words differ from author to author, as do the specific bicategories
considered. We propose a unified framework: by working with monads on double
categories and related structures (rather than bicategories), one can define
generalized multicategories in a way that unifies all previous examples, while
at the same time simplifying and clarifying much of the theory.Comment: 76 pages; final version, to appear in TA
Parametrized spaces model locally constant homotopy sheaves
We prove that the homotopy theory of parametrized spaces embeds fully and
faithfully in the homotopy theory of simplicial presheaves, and that its
essential image consists of the locally homotopically constant objects. This
gives a homotopy-theoretic version of the classical identification of covering
spaces with locally constant sheaves. We also prove a new version of the
classical result that spaces parametrized over X are equivalent to spaces with
an action of the loop space of X. This gives a homotopy-theoretic version of
the correspondence between covering spaces over X and sets with an action of
the fundamental group of X. We then use these two equivalences to study base
change functors for parametrized spaces.Comment: 26 pages; exposition improve
Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase
Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR
Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.
Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool
Reversal of Hypertriglyceridemia, Fatty Liver Disease, and Insulin Resistance by a Liver-Targeted Mitochondrial Uncoupler
SummaryNonalcoholic fatty liver disease (NAFLD) affects one in three Americans and is a major predisposing condition for the metabolic syndrome and type 2 diabetes (T2D). We examined whether a functionally liver-targeted derivative of 2,4-dinitrophenol (DNP), DNP-methyl ether (DNPME), could safely decrease hypertriglyceridemia, NAFLD, and insulin resistance without systemic toxicities. Treatment with DNPME reversed hypertriglyceridemia, fatty liver, and whole-body insulin resistance in high-fat-fed rats and decreased hyperglycemia in a rat model of T2D with a wide therapeutic index. The reversal of liver and muscle insulin resistance was associated with reductions in tissue diacylglycerol content and reductions in protein kinase C epsilon (PKCε) and PKCθ activity in liver and muscle, respectively. These results demonstrate that the beneficial effects of DNP on hypertriglyceridemia, fatty liver, and insulin resistance can be dissociated from systemic toxicities and suggest the potential utility of liver-targeted mitochondrial uncoupling agents for the treatment of hypertriglyceridemia, NAFLD, metabolic syndrome, and T2D
Connecting Biology and Mathematics: First Prepare the Teachers
Developing the connection between biology and mathematics is one of the most important ways to shift the paradigms of both established science disciplines. However, adding some mathematic content to biology or biology content to mathematics is not enough but must be accompanied by development of suitable pedagogical models. I propose a model of pedagogical mathematical biological content knowledge as a feasible starting point for connecting biology and mathematics in schools and universities. The process of connecting these disciplines should start as early as possible in the educational process, in order to produce prepared minds that will be able to combine both disciplines at graduate and postgraduate levels of study. Because teachers are a crucial factor in introducing innovations in education, the first step toward such a goal should be the education of prospective and practicing elementary and secondary school teachers
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