Mencari Keindahan Dalam Catan Chuah Thean Teng: Kajian Awal Analisis Geometri

Banyak kata indah digunakan untuk mengungkap visual yang terlihat pada sesebuah catan. Kata indah yang dimaksudkan ini adalah keteraturan dan keseimbangan berdasarkan prinsip geometri. Makalah ini akan mengkhususkan untuk mengenalpasti struktur tersembunyi yang terdapat dalam karya Chuah Thean Teng. Karya yang dipilih ialah catan medium batik yang bertajuk ‘Joy of Living’. Analisis geometri dgunakan sebagai alat dalam mengkaji struktur ini. Struktur tersembunyi ini ditentuluarkan, dianalisis serta diterangkan komposisi gubahan imej catan ini. Kajian awal analisis geometri ini diharapkan memberi lebih pemahaman terhadap gubahan struktur visual bagi membuat dokumentasi terhadap sejarah seni lukis Malaysi

Prenatal chromosomal diversification of leukemia in monozygotic twins

Previous studies on concordant acute lymphoblastic leukemia (ALL) in identical twins have identified the leukemia as monoclonal with MLL or ETV6-RUNX1 gene fusion as early or initiating events in utero. In the latter case, postnatal latency is associated with secondary genetic events such as ETV6 deletion. We describe here a pair of infant twins with concordant acute monoblastic leukemia (AML). They are a unique pair in that their leukemia blasts display extensive intraclonal chromosomal diversity. Comparison of the leukemic cells between the two twins by karyotype and fluorescence in situ hybridization identifies a common or shared stem line and extensive subclonal diversity for which the twins\u27 leukemic populations are divergent. This case of leukemia illustrates in utero initiation with early imposition of chromosomal instability, the progressively divergent evolution of which can be mapped in the twins into pre- and postnatal periods

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models. Furthermore, tofacitinib strongly synergized with venetoclax in coculture with bone marrow stromal cells but not in monoculture. Surprisingly, we found that ruxolitinib, an FDA approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. Transcriptome analysis and unbiased phosphoproteomics revealed that bone marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib reverses the growth-promoting effects of the tumor microenvironment. As tofacitinib is already FDA approved, these results can be rapidly translated into potential clinical benefits for myeloma patients

Detection of missense mutations by single-strand conformational polymorphism (SSCP) analysis in five dysfunctional variants of coagulation factor VII

Five unrelated subjects with dysfunctional coagulation factor VII (FVII) were studied In order to Identify missense mutations affecting function. Exons 2 to 8 and the Intron-exon Junctions of their FVIl genes were amplified from peripheral white blood cell DNA by PCR and screened by SSCP analysis. DNA fragments showing aberrant mobility were sequenced. The following mutations were Identified: In case 1 (FVII: C <1%, FVIl:Ag 18%) a heterozygous A to G transltion at nucleotlde 8915 In exon 6 results In the amlno acid substitution Lys-137 to Glu near the C-termlnus of the FVlla llght chaln; In case 2 (FVII: C 7%, FVll:Ag 47%) a heterozygous A to G transltion at nucleotide 7834 In exon 5 results in the substitution of Gin-100 by Arg in the second EGF-like domain; In case 3 (FVll:C 20%, FVIl:Ag 76%) a homozygous G to A transition at nucleotide position 6055 in exon 4 was detected resulting in substitution of Arg-79 by Gin in the first EGF-like domain; in case 5 (FVIl:C 10%, FVIl:Ag 52%) a heterozygous C to T transition at nucleotide position 6054 in exon 4 also results in the substitution of Arg79, but in this case it is replaced by Trp; case 4 (FVll:C <1%, FVIl:Ag 100%) was homozygous for a previously reported mutation (G to A) at nucleotide position 10715 in exon 8, substituting Gin for Arg at position 304 in the protease domain. Cases 1,2 and 5 evidently have additional undetected mutation

The Causes of Foehn Warming in the Lee of Mountains

The foehn effect is well known as the warming, drying, and cloud clearance experienced on the lee side of mountain ranges during “flow over” conditions. Foehn flows were first described more than a century ago when two mechanisms for this warming effect were postulated: an isentropic drawdown mechanism, where potentially warmer air from aloft is brought down adiabatically, and a latent heating and precipitation mechanism, where air cools less on ascent—owing to condensation and latent heat release—than on its dry descent on the lee side. Here, for the first time, the direct quantitative contribution of these and other foehn warming mechanisms is shown. The results suggest a new paradigm is required after it is demonstrated that a third mechanism, mechanical mixing of the foehn flow by turbulence, is significant. In fact, depending on the flow dynamics, any of the three warming mechanisms can dominate. A novel Lagrangian heat budget model, back trajectories, high-resolution numerical model output, and aircraft observations are all employed. The study focuses on a unique natural laboratory—one that allows unambiguous quantification of the leeside warming—namely, the Antarctic Peninsula and Larsen C Ice Shelf. The demonstration that three foehn warming mechanisms are important has ramifications for weather forecasting in mountainous areas and associated hazards such as ice shelf melt and wildfires

A Divergent Synthetic Approach to Diverse Molecular Scaffolds: Assessment of Lead-Likeness using LLAMA, an Open-Access Computational Tool

Complementary cyclisation reactions of hex-2-ene-1,6-diamine derivatives were exploited in the synthesis of alternative molecular scaffolds. The value of the synthetic approach was analysed using LLAMA, an open-access computational tool for assessing the lead-likeness and novelty of molecular scaffolds

Assessment of Survivor Concerns (ASC): A newly proposed brief questionnaire

BACKGROUND: The purpose of this study was to design a brief questionnaire to measure fears about recurrence and health in cancer survivors. Research involving fear of recurrence has been increasing, indicating that it is an important concern among cancer survivors. METHODS: We developed and tested a six-item instrument, the Assessment of Survivor Concerns (ASC). Construct validity was examined in a multiple group confirmatory factor analysis (CFA) with 592 short-term and 161 long-term cancer survivors. Convergent and discriminant validity was examined through comparisons with the PANAS (Positive and Negative Affect Schedule) and the CES-D (Center for Epidemiologic Studies Depression) measures. RESULTS: CFA models for the ASC with short- and long-term survivors showed good fit, with equivalent structure across both groups of cancer survivors. Convergent and discriminant validity was also supported through analyses of the PANAS and CES-D. One item (children's health worry) did not perform as well as the others, so the models were re-run with the item excluded, and the overall fit was improved. CONCLUSION: The ASC showed excellent internal consistency and validity. We recommend the revised five-item instrument as an appropriate measure for assessment of cancer survivor worries

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A unified lead-oriented synthesis of over fifty molecular scaffolds

Controlling the properties of lead molecules is critical in drug discovery, but sourcing large numbers of lead-like compounds for screening collections is a major challenge. A unified synthetic approach is described that enabled the synthesis of 52 diverse lead-like molecular scaffolds from a minimal set of 13 precursors. The divergent approach exploited a suite of robust, functional group-tolerant transformations. Crucially, after derivatisation, these scaffolds would target significant lead-like chemical space, and complement commercially-available compounds