Undergraduate Mathematics Students' Understanding of the Concept of Function

Concern has been expressed that many commencing undergraduate mathematics students have mastered skills without conceptual understanding. A pilot study carried out at a leading Australian university indicates that a significant number of students, with high tertiary entrance ranks, have very limited understanding of the concept of function, despite the emphasis it receives in the secondary mathematics curriculum. Whilst most students were familiar with families of functions, many were unable to give an appropriate definition or recognize whether a given graph or rule represents a function; and could not make correct connections between function graphs and tables of values

Phase II study of Gemcitabine and Curcumin (Meriva®) as first line treatment for locally advanced or metastatic pancreatic cancer: preliminary results

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Expression of CCL9/MIP-1γ is repressed by BCR/ABL and its restoration suppresses in vivo leukemogenesis of 32D-BCR/ABL cells

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LPMLE3 : a novel 1-D approach to study water flow in streambeds using heat as a tracer

We introduce LPMLE3, a new 1-D approach to quantify vertical water flow components at streambeds using temperature data collected in different depths. LPMLE3 solves the partial differential equation for coupled water flow and heat transport in the frequency domain. Unlike other 1-D approaches it does not assume a semi-infinite halfspace with the location of the lower boundary condition approaching infinity. Instead, it uses local upper and lower boundary conditions. As such, the streambed can be divided into finite subdomains bound at the top and bottom by a temperature-time series. Information from a third temperature sensor within each subdomain is then used for parameter estimation. LPMLE3 applies a low order local polynomial to separate periodic and transient parts (including the noise contributions) of a temperature-time series and calculates the frequency response of each subdomain to a known temperature input at the streambed top. A maximum-likelihood estimator is used to estimate the vertical component of water flow, thermal diffusivity, and their uncertainties for each streambed subdomain and provides information regarding model quality. We tested the method on synthetic temperature data generated with the numerical model STRIVE and demonstrate how the vertical flow component can be quantified for field data collected in a Belgian stream. We show that by using the results in additional analyses, nonvertical flow components could be identified and by making certain assumptions they could be quantified for each subdomain. LPMLE3 performed well on both simulated and field data and can be considered a valuable addition to the existing 1-D methods

The effect of timing and composition of gestational weight gain in obese pregnant women on infant birth weight: A prospective cohort study.

Introduction: CK2 is a protein kinase implicated in several essential cellular processes, over-expressed in cancer and described to regulate insulin signaling cascade. Recently CK2 has been described to negatively regulate thermogenesis (Shinoda K et al, 2015, Cell Metabolism) and to inhibit insulin release (Rossi M et al, 2015, PNAS). Nevertheless, the role of CK2 in adipose tissue (AT) and its involvement in human obesity development and therapy has been poorly investigated. Methods: Our multi-disciplinary team performed biochemical analysis of signaling pathways by WB and in vitro kinase activity assays, and glucose handling studies using glucose uptake assay and IF in adipocyte cultures and glucose and insulin tolerance test in mice. Moreover we quantify CK2 expression/activity in human AT specimens of 27 obese patients, clinically characterized, in 12 obese patients underwent relevant weight loss and 11 normal-weight controls. Results: We proved that CK2 amount and activity were not influenced by insulin stimulation and that CK2 activity was efficiently inhibited by specific inhibitors, structurally unrelated. We worked with CX-4945, a CK2 inhibitor currently used in cancer clinical trials, using the minimal concentration (2.5 \u192 dM) and pre-treatment time (1hr) able to efficiently inhibit CK2 activity, avoiding any cytotoxic effect. Pharmacological inhibition of CK2 did not significantly affect in vitro adipogenic differentiation or expression profiling of mature adipocytes. Conversely, we showed that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. We compared CK2 expression and activity in different mouse tissues highlighted that white skeletal muscle fibres and liver contained the highest quantity of this kinase. CK2 was expressed more in brown AT than in white AT depots. We show that CK2 promotes insulin-signaling in mouse AT, liver and skeletal muscle and that in vivo acute treatment with CX-4945 impairs glucose- tolerance in mice. Studies in tissues of ob/ob and db/db mice highlights an up-regulation of CK2 expression and activity only in WAT. CK2 hyper-activation is strongly evident also in SAT and VAT of obese patients and weight loss obtained by bariatric surgery or hypocaloric diet reverts CK2 up-regulation to normal level. Conclusion: We show that CK2 is involved in insulin sensitivity, glucose handling and remodeling of WAT. Moreover we identify CK2 hyper-activation as a hallmark of human obesity, suggesting a new potential therapeutic target for metabolic diseases

PO-315 The mutational and transcriptome landscape of infant B-cell acute lymphoblastic leukaemia: the INTERFANT treatment protocol experience

Introduction Infant B-cell precursor acute lymphoblastic leukaemia (iBCP-ALL) has dismal prognosis, especially with MLLgene rearrangements (MLLr) which are hallmark clonal leukemogenic drivers. Molecular pathogenesis of MLLr-iBCP-ALL remain somehow enigmatic and in vivo recreation of MLLriBCP-ALL is challenging. Material and methods We performed whole-genome, exome, targetted and RNA-sequencing on an Interfant study discovery cohort of 50 iBCP-ALLs (27MLL-AF4+, including relapses, 5MLL-AF9+and 10non-MLL). An independent validation cohort of 82iBCP-ALLs (43MLL-AF4+, 11MLL-AF9+, and 28non-MLL) was used for targeted DNA-sequencing/qRT-PCR. Results and discussions iBCP-ALL shows an extremely low frequency of somatic mutations, irrespective of the presence/subtype of MLLr, with the predominant leukemic clone carrying a mean of 2.5 non-silent mutations. Recurrent mutations were exclusively found in KRAS and NRAS, which were more frequent in the MLL-AF4+than in MLL-AF9+/non-MLL iBCPALL due to common NRAS mutations found in MLL-AF4 +infants (32% vs 6%; p Conclusion iBCP-ALL shows a silent mutational landscape regardless the MLL status. The expression of AF4-MLL associates to a better prognosis and specific upregulation of HOXA cluster genes. A pre-BCR early progenitor/stem cell may represent the cell-of-origin for both the t(4;11) and RAS mutations

Enantiopure Dinaphtho[2,3-b:2,3-f]thieno[3,2-b]thiophenes: Reaching High Magnetoresistance Effect in OFETs

Chiral molecules are known to behave as spin filters due to the chiral induced spin selectivity (CISS) effect. Chirality can be implemented in molecular semiconductors in order to study the role of the CISS effect in charge transport and to find new materials for spintronic applications. In this study, the design and synthesis of a new class of enantiopure chiral organic semiconductors based on the well-known dinaphtho[2,3-b:2,3-f]thieno[3,2-b]thiophene (DNTT) core functionalized with chiral alkyl side chains is presented. When introduced in an organic field-effect transistor (OFET) with magnetic contacts, the two enantiomers, (R)-DNTT and (S)-DNTT, show an opposite behavior with respect to the relative direction of the magnetization of the contacts, oriented by an external magnetic field. Each enantiomer displays an unexpectedly high magnetoresistance over one preferred orientation of the spin current injected from the magnetic contacts. The result is the first reported OFET in which the current can be switched on and off upon inversion of the direction of the applied external magnetic field. This work contributes to the general understanding of the CISS effect and opens new avenues for the introduction of organic materials in spintronic devices

A computational approach to identify whole genome homozygosity mapping across multiple SNP mapping experiments

The recent development of microarray platforms, capable to genotype more than thousands of single nucleotide polymorphisms (SNPs) in individuals, had provided an opportunity to rapidly identify susceptibility loci for complex phenotypes. High density SNP mapping arrays have been widely applied to association studies, to copy number (CN) analysis in cancers and recently to investigate the role of homozygosity extended regions in individuals. Long stretches of CN neutral and homozygous SNPs, defined as runs of homozygosity (ROHs) can be found either in a single individual or shared across samples. The identification of ROHs among affected individuals of the same family or among unrelated ones with same disease, can underline loci potentially implicated in the genetic basis of the disease under study. Therefore the identification of ROHs in affected individuals or pathological datasets gives a chance to identify disease associated loci and new causative mutations. In order to identify ROHs pattern across Affymetrix SNP mapping datasets, we developed a computational strategy including several computational steps: 1) loss of heterozygosity analysis by dChip2007 software; 2) a within-subject step allowing the identification of ROHs in a single sample; 3) an across-subject step extracting the ROH fingerprint of the dataset and 4) the identification of a common ROHs pattern based on frequency across the dataset under study, varying the number of individuals carrying common ROHs; 5) the annotation step allowing the association of genes to selected ROHs. In order to obtain an effective ROHs visualization, we use dChip software for the entire samples dataset. We assess our strategy to two SNP mapping datasets including 100K leukemia and 250K congenital recessive diseases. The procedure allowed the identification of a unique genetic ROH fingerprint of clinical datasets potentially important to discover new diseases associated loci suitable for further investigations