The clathrin-binding domain of CALM-AF10 alters the phenotype of myeloid neoplasms in mice.

The PICALM (CALM) gene, whose product is involved in clathrin-mediated endocytosis, has been identified in two recurring chromosomal translocations, involving either MLL or MLLT10 (AF10). We developed a mouse model of CALM-AF10(+) leukemia to examine the hypothesis that disruption of endocytosis contributes to leukemogenesis. Exclusion of the C-terminal portion of CALM from the fusion protein, which is required for optimal binding to clathrin, resulted in the development of a myeloproliferative disease, whereas inclusion of this domain led to the development of acute myeloid leukemia and changes in gene expression of several cancer-related genes, notably Pim1 and Crebbp. Nonetheless, the development of leukemia could not be attributed directly to interference with endocytosis or consequential changes in proliferation and signaling. In leukemia cells, full-length CALM-AF10 localized to the nucleus with no consistent effect on growth factor endocyctosis, and suppressed histone H3 lysine 79 methylation regardless of the presence of clathrin. Using fluorescence resonance energy transfer analysis, we show that CALM-AF10 has a propensity to homo-oligomerize, raising the possibility that the function of endocytic proteins involved in chimeric fusions may be to provide dimerization properties, a recognized mechanism for unleashing oncogenic properties of chimeric transcription factors, rather than disrupting the internalization of growth factor receptors

Aircraft energy efficiency laminar flow control wing design study

An engineering design study was performed in which laminar flow control (LFC) was integrated into the wing of a commercial passenger transport aircraft. A baseline aircraft configuration was selected and the wing geometry was defined. The LFC system, with suction slots, ducting, and suction pumps was integrated with the wing structure. The use of standard aluminum technology and advanced superplastic formed diffusion bonded titanium technology was evaluated. The results of the design study show that the LFC system can be integrated with the wing structure to provide a structurally and aerodynamically efficient wing for a commercial transport aircraft

The Value of Comparative Animal Research : Krogh’s Principle Facilitates Scientific Discoveries

There are no conflicts of interest to declare. This paper developed from the 2016 Early Career Impact Award from the Federation of Associations in Behavioral & Brain Sciences to TJS. TJS has received funding from The Leverhulme Trust. FJPE is in receipt of funding from the BBSRC (BB/M001555/1). The National Institutes of Health has funded RDF (NS 034950, NS093277, NIMH 087930), AGO (HD079573, IOS-1354760) and AMK (HD081959). BAA is an Arnold O. Beckman postdoctoral fellow.Peer reviewedPostprin

When half a word is enough: infants can recognize spoken words using partial phonetic information

Adults process speech incrementally, rapidly identifying spoken words on the basis of initial phonetic information sufficient to distinguish them from alternatives. In this study, infants in the second year also made use of word-initial information to understand fluent speech. The time course of comprehension was examined by tracking infants' eye movements as they looked at pictures in response to familiar spoken words, presented both as whole words in intact form and as partial words in which only the first 300 ms of the word was heard. In Experiment 1, 21-month-old infants (N = 32) recognized partial words as quickly and reliably as they recognized whole words; in Experiment 2, these findings were replicated with 18-month-old infants (N = 32). Combining the data from both experiments, efficiency in spoken word recognition was examined in relation to level of lexical development. Infants with more than 100 words in their productive vocabulary were more accurate in identifying familiar words than were infants with less than 60 words. Grouped by response speed, infants with faster mean reaction times were more accurate in word recognition and also had larger productive vocabularies than infants with slower response latencies. These results show that infants in the second year are capable of incremental speech processing even before entering the vocabulary spurt, and that lexical growth is associated with increased speed and efficiency in understanding spoken language

Freire re-viewed

The work of Paulo Freire is associated with themes of oppression and liberation, and his critical pedagogy is visionary in its attempts to bring about social transformation. Freire has created a theory of education that embeds these issues within social relations that center around both ideological and material domination. In this review essay, Sue Jackson explores three books: Freire’s final work Pedagogy of Indignation; Cesar Augusto Rossatto’s Engaging Paulo Freire’s Pedagogy of Possibility, which attempts to engage Freire’s pedagogy of possibility; and C.A. Bowers and Frederique Apffel-Marglin’s edited collection Re-thinking Freire, which asks readers to reconsider Freire’s work in light of globalization and environmental crises. Jackson questions the extent to which Freire’s pedagogical approaches are useful to educators as well as to “the oppressed,” and whether challenges to re-think Freire can lead to new kinds of critical pedagogies

Oportunidades Program Participation and Body Mass Index, Blood Pressure, and Self-Reported Health in Mexican Adults

IntroductionGovernments around the world are seeking to address the increasing prevalence of obesity and hypertension. Our objective was to evaluate the effect of an incentive-based development program (Oportunidades, formerly Progresa) on body mass index (BMI), blood pressure, and self-reported health.MethodsAn intervention group of low-income (below the 20th percentile nationally), rural, Mexican adults (aged 30-65 years) (n = 5280) received program benefits (cash transfers contingent on positive changes in health behavior such as regular health checkups) for 3.5 to 5.0 years. They were compared with a newly recruited control group of adults (n = 1063) who had not yet begun receiving benefits. Analyses were adjusted for almost 50 social and economic covariates.ResultsAge- and sex-adjusted BMI was lower in adults from intervention communities than in those from control communities (26.57 kg/m(2) vs 27.16 kg/m(2), P < .001), as was the prevalence of obesity (20.28% vs 25.31%, P < .001) and overweight (59.24% vs 63.04%, P = .03); these results were attenuated after covariates were included. Adults in intervention communities had a lower combined prevalence of uncontrolled hypertension (33.80% vs 34.52%, P = .008) when adjusting for all covariates. Mean systolic (beta = -2.60, P < .001) and diastolic (beta = -2.84, P < .001) blood pressures were significantly lower in the intervention communities after all covariates were included, and self-reported health outcomes were better.ConclusionParticipation in Oportunidades, a large-scale cash-transfer program, was associated with lower prevalence of obesity and hypertension and better self-reported health in adults in rural Mexico

Three Able Addresses Delivered Before the State Board of Trade at Bangor, Maine, March 25, 1902

The text of three addresses: Maine canning industry / B.M. Fernald -- Maine as a vacation state / Leroy T. Carleton -- Maine primitive and modern industry / J.W. Penney

A General-Equilibrium Asset-Pricing Approach to the Measurement of Nominal and Real Bank Output

This paper addresses the proper measurement of financial service output that is not priced explicitly. It shows how to impute nominal service output from financial intermediaries' interest income, and how to construct price indices for those financial services. We model financial intermediaries as providers of financial services which resolve asymmetric information between borrowers and lenders. We embed these intermediaries in a dynamic, stochastic, general-equilibrium model where assets are priced competitively according to their systematic risk, as in the standard consumption-based capital-asset-pricing model. In this environment, we show that it is critical to take risk into account in order to measure financial output accurately. We also show that even using a risk-adjusted reference rate does not solve all the problems associated with measuring nominal financial service output. Our model allows us to address important outstanding questions in output and productivity measurement for financial firms, such as: (1) What are the correct "reference rates" to use in calculating bank output? In particular, should they take account of risk? (2) If reference rates need to be risk-adjusted, should they be ex ante or ex post rates of return? (3) What is the right price deflator for the output of financial firms? Is it just the general price index? (4) When--if ever--should we count capital gains of financial firms as part of financial service output?