212 research outputs found
Code or (Not Code): Separating Formal and Natural Language in CS Education
This paper argues that the "institutionalised understanding" of pseudo-code as a blend of formal and natural languages makes it an unsuitable choice for national assessment where the intention is to test program comprehension skills. It permits question-setters to inadvertently introduce a level of ambiguity and consequent confusion. This is not in keeping with either good assessment practice or an argument developed in the paper that CS education should be clearly fostering the skills needed for understanding formal, as distinct from natural, languages. The argument is backed up by an analysis of 49 questions drawn from the national school CS examinations of a single country, spanning a period of six years and two phases -- the first in which no formal pseudo-code was defined, the second in which a formal reference language, referred to as a "formally-defined pseudo-code", was provided for teachers and exam setters. The analysis demonstrates that in both phases, incorrect, confusing or ambiguous code was presented in questions. The paper concludes by recommending that the term reference language should be used in place of pseudo-code, and an appropriate formally-defined language specified, in national exam settings where a common language of assessment is required. This change of terms emphasises the characteristics required of a language to be used for assessment of program comprehension. The reference language used in the study is outlined. It was designed by the authors for human readability and also to make absolutely explicit the demarcation between formal and informal language, in such a way that automated checking can be carried out on programs written in the language. Formal specifications and a checker for the language are available
Physical capacity in physically active and non-active adolescents
Aim: The aim of this study was to investigate differences in physical capacity between physically active and non-active men and women among graduates from upper secondary school. Subject and methods: Research participants were graduates (38 women and 61 men) from upper secondary school. Physical activity was determined using the International Physical Activity Questionnaire, and participants were dichotomously characterized as being physically active or physically non-active according to the recommendations of the World Health Organization (WHO). Aerobic capacity was measured using the Åstrand cycle ergometer test. Participants also underwent tests of muscular strength and balance. Results: Maximum oxygen uptake differed significantly between physically active and non-active men (mean ± SD 3.6 ± 0.7 vs 3.0 ± 0.6 l/kg, p = 0.002) and women (3.0 ± 0.6 vs 2.5 ± 0.3 l/kg, p = 0.016). There was a difference among physically active and non-active men regarding push-ups (37.1 ± 9.0 vs 28.5 ± 7.0, p < 0.001) and sit-ups (59.2 ± 30.2 vs 39.6 ± 19.4, p = 0.010). No significant differences were found regarding vertical jump or grip strength among men, any of the muscle strength measurements among women, and balance (in any sex). Conclusion: Activity levels had impact on aerobic capacity in both sexes, but did not seem to have the same impact on muscular strength and balance, especially in women
p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2.
Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is required for the embryonic formation of the cerebral cortex. Here we show that Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting Akirin2 loss to excitatory cortical neurons resulted in progressive neurodegeneration via necroptosis and severe cortical atrophy with age. Comparing transcriptomes from Akirin2-null postnatal neurons and cortical progenitors revealed that targets of the tumor suppressor p53, a regulator of both proliferation and cell death encoded b
Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes
Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling
14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins
Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins
Estimation of the spontaneous mutation rate in Heliconius melpomene
This is the final published version. It first appeared at mbe.oxfordjournals.org/content/early/2014/11/03/molbev.msu302.abstract.We estimated the spontaneous mutation rate in Heliconius melpomene by genome sequencing of\ud
a pair of parents and 30 of their offspring, based on the ratio of number of de novo heterozygotes\ud
to the number of callable site-individuals. We detected nine new mutations, each one affecting a\ud
single site in a single offspring. This yields an estimated mutation rate of 2.9 x 10-9 (95%\ud
confidence interval, 1.3 x 10-9 - 5.5 x 10-9), which is similar to recent estimates in Drosophila\ud
melanogaster, the only other insect species in which the mutation rate has been directly estimated.\ud
We infer that recent effective population size of H. melpomene is about 2 million, a substantially\ud
lower value than its census size, suggesting a role for natural selection reducing diversity. We\ud
estimate that H. melpomene diverged from its M?llerian co-mimic H. erato about 6 MYA, a\ud
somewhat later date than estimates based on a local molecular clock.CJ was funded by BBSRC [H01439X/1], JWD was funded by the Herchel Smith Fund and PDK and\ud
RWN were funded by the BBSRC
Stromal Cell-Derived Factor-1/CXCL12 Contributes to MMTV-Wnt1 Tumor Growth Involving Gr1+CD11b+ Cells
BACKGROUND: Histological examinations of MMTV-Wnt1 tumors reveal drastic differences in the tumor vasculature when compared to MMTV-Her2 tumors. However, these differences have not been formally described, nor have any angiogenic factors been implicated to be involved in the Wnt1 tumors. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that MMTV-Wnt1 tumors were more vascularized than MMTV-Her2 tumors, and this correlated with significantly higher expression of a CXC chemokine, stromal cell-derived factor-1 (SDF1/CXCL12) but not with VEGFA. Isolation of various cell types from Wnt1 tumors revealed that SDF1 was produced by both tumor myoepithelial cells and stromal cells, whereas Her2 tumors lacked myoepithelial cells and contained significantly less stroma. The growth of Wnt1 tumors, but not Her2 tumors, was inhibited by a neutralizing antibody to SDF1, but not by neutralization of VEGFA. Anti-SDF1 treatment decreased the proportion of infiltrating Gr1(+) myeloid cells in the Wnt1 tumors, which correlated with a decrease in the percentage of endothelial cells. The involvement of Gr1(+) cells was evident from the retardation of Wnt1 tumor growth following in vivo depletion of these cells with an anti-Gr1-specific antibody. This degree of inhibition on Wnt1 tumor growth was comparable, but not additive, to the effect observed with anti-SDF1, indicative of overlapping mechanisms of inhibition. In contrast, Her2 tumors were not affected by the depletion of Gr1(+) cells. CONCLUSIONS/SIGNIFICANCE: We demonstrated that SDF1 is important for Wnt1, but not for HER2, in inducing murine mammary tumor and the role of SDF1 in tumorigenesis involves Gr1(+) myeloid cells to facilitate growth and/or angiogenesis
Committee II: Guidelines for cytologic sampling techniques of lung and mediastinal lymph nodes
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146505/1/dc23975.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146505/2/dc23975_am.pd
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