Phonological awareness in native Cantonese-speaking children with different English competences

"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, April 30, 1997."Also available in print.Thesis (B.Sc)--University of Hong Kong, 1997published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Attenuated transcriptional response to pro-inflammatory cytokines in schizophrenia hiPSC-derived neural progenitor cells

Maternal immune activation (MIA) during prenatal development is an environmental risk factor for psychiatric disorders including schizophrenia (SZ). Converging lines of evidence from human and animal model studies suggest that elevated cytokine levels in the maternal and fetal compartments are an important indication of the mechanisms driving this association. However, there is variability in susceptibility to the psychiatric risk conferred by MIA, likely influenced by genetic factors. How MIA interacts with a genetic profile susceptible to SZ is challenging to test in animal models. To address this gap, we examined whether differential gene expression responses occur in forebrain-lineage neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSC) generated from three individuals with a diagnosis of schizophrenia and three healthy controls. Following acute (24 h) treatment with either interferon-gamma (IFNγ; 25 ng/μl) or interleukin (IL)-1β (10 ng/μl), we identified, by RNA sequencing, 3380 differentially expressed genes (DEGs) in the IFNγ-treated control lines (compared to untreated controls), and 1980 DEGs in IFNγ-treated SZ lines (compared to untreated SZ lines). Out of 4137 genes that responded significantly to IFNγ across all lines, 1223 were common to both SZ and control lines. The 2914 genes that appeared to respond differentially to IFNγ treatment in SZ lines were subjected to a further test of significance (multiple testing correction applied to the interaction effect between IFNγ treatment and SZ diagnosis), yielding 359 genes that passed the significance threshold. There were no differentially expressed genes in the IL-1β-treatment conditions after Benjamini-Hochberg correction. Gene set enrichment analysis however showed that IL-1β impacts immune function and neuronal differentiation. Overall, our data suggest that a) SZ NPCs show an attenuated transcriptional response to IFNγ treatment compared to controls; b) Due to low IL-1β receptor expression in NPCs, NPC cultures appear to be less responsive to IL-1β than IFNγ; and c) the genes differentially regulated in SZ lines – in the face of a cytokine challenge – are primarily associated with mitochondrial, “loss-of-function”, pre- and post-synaptic gene sets. Our findings particularly highlight the role of early synaptic development in the association between maternal immune activation and schizophrenia risk

A Hierarchical Tracking Strategy for Vision-Based Applications On-Board UAVs

In this paper, we apply a hierarchical tracking strategy of planar objects (or that can be assumed to be planar) that is based on direct methods for vision-based applications on-board UAVs. The use of this tracking strategy allows to achieve the tasks at real-time frame rates and to overcome problems posed by the challenging conditions of the tasks: e.g. constant vibrations, fast 3D changes, or limited capacity on-board. The vast majority of approaches make use of featurebased methods to track objects. Nonetheless, in this paper we show that although some of these feature-based solutions are faster, direct methods can be more robust under fast 3D motions (fast changes in position), some changes in appearance, constant vibrations (without requiring any specific hardware or software for video stabilization), and situations in which part of the object to track is outside of the field of view of the camera. The performance of the proposed tracking strategy onboard UAVs is evaluated with images from realflight tests using manually-generated ground truthinformation, accurate position estimation using a Vicon system, and also with simulated data from a simulation environment. Results show that the hierarchical tracking strategy performs better than well-known feature-based algorithms and wellknown configurations of direct methods, and that its performance is robust enough for vision-in-theloop tasks, e.g. for vision-based landing tasks

″Minor″ BCL2 Breakpoints in Follicular Lymphoma : Frequency and Correlation with Grade and Disease Presentation in 236 Cases

Follicular lymphomas are frequently associated with the t(14;18)(q32;q21). This translocation can be detected by karyotype, polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH). In addition to the breakpoints currently used for diagnosis located in the major breakpoint region (MBR) and the minor cluster region (mcr), recent studies have reported the existence of other breakpoints (3′ BCL2, 5′mcr, and icr). In this study, we examined the frequency of all five breakpoints in 236 cases of follicular lymphomas by real-time PCR analysis. The distribution of breakpoint sites consisted of MBR in 118 cases (50%), mcr in 11 (5%), icr in 32 (13%), 3′ BCL2 in 13 (6%), and 5′ mcr in three cases (1%). These findings illustrate significantly higher frequency of the icr breakpoint as compared with the more frequently studied mcr. Correlation of breakpoints with histology showed that MBR breakpoints occur more frequently in grade 2 lymphomas (P = 0.042). A majority of the PCR-negative cases (75%) contained an IGH/BCL2 translocation with FISH methods, suggesting the presence of other BCL2 breakpoints. Correlation of breakpoints with survival did not reveal significant differences. Diagnostic laboratories should consider expanding their PCR methods to include other BCL2 breakpoints and correlating with FISH methods when appropriate

PKA Regulates Vacuolar H+-ATPase Localization and Activity via Direct Phosphorylation of the A Subunit in Kidney Cells*

The vacuolar H+-ATPase (V-ATPase) is a major contributor to luminal acidification in epithelia of Wolffian duct origin. In both kidney-intercalated cells and epididymal clear cells, cAMP induces V-ATPase apical membrane accumulation, which is linked to proton secretion. We have shown previously that the A subunit in the cytoplasmic V1 sector of the V-ATPase is phosphorylated by protein kinase A (PKA). Here we have identified by mass spectrometry and mutagenesis that Ser-175 is the major PKA phosphorylation site in the A subunit. Overexpression in HEK-293T cells of either a wild-type (WT) or phosphomimic Ser-175 to Asp (S175D) A subunit mutant caused increased acidification of HCO3−-containing culture medium compared with cells expressing vector alone or a PKA phosphorylation-deficient Ser-175 to Ala (S175A) mutant. Moreover, localization of the S175A A subunit mutant expressed in HEK-293T cells was more diffusely cytosolic than that of WT or S175D A subunit. Acute V-ATPase-mediated, bafilomycin-sensitive H+ secretion was up-regulated by a specific PKA activator in HEK-293T cells expressing WT A subunit in HCO3−-free buffer. In cells expressing the S175D mutant, V-ATPase activity at the membrane was constitutively up-regulated and unresponsive to PKA activators, whereas cells expressing the S175A mutant had decreased V-ATPase activity that was unresponsive to PKA activation. Finally, Ser-175 was necessary for PKA-stimulated apical accumulation of the V-ATPase in a polarized rabbit cell line of collecting duct A-type intercalated cell characteristics (Clone C). In summary, these results indicate a novel mechanism for the regulation of V-ATPase localization and activity in kidney cells via direct PKA-dependent phosphorylation of the A subunit at Ser-175

The Rise and Fall of Ziggy Stardust and Natural Law

In Natural Law and Natural Rights, John Finnis delves into the past, attempting to revitalise the Thomist natural law tradition cut short by opposing philosophers such as David Hume. In this article, Finnis’s efforts at revival are assessed by way of comparison with—and, indeed, contrast to—the life and art of musician David Bowie. In spite of their extravagant differences, there exist significant points of connection that allow Bowie to be used in interpreting Finnis’s natural law. Bowie’s work—for all its appeals to a Nietzschean ground zero for normative values—shares Finnis’s concern with ordering affairs in a way that will realise humanity’s great potential. In presenting enchanted worlds and evolved characters as an antidote to all that is drab and pointless, Bowie has something to tell his audience about how human beings can thrive. Likewise, natural law holds that a legal system should include certain content that guides people towards a life of “flourishing”. Bowie and Finnis look to the past, plundering it for inspiration and using it as fuel to boost humankind forward. The analogy of Natural Law and Natural Rights and Bowie’s magpie-like relationship to various popular music traditions ultimately reveals that natural law theory is not merely an objective and unchanging edict to be followed without question, but a legacy that is to be recreated by those who carry it into the future. Law’s instruments of critique must not forget these transformative qualities.Arts, Education & Law Group, School of LawFull Tex

Representative sequencing: Unbiased sampling of solid tumor tissue

International audienceAlthough thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure