Berita Special Spring Issue 2015

Table of Contents Editor’s Foreword...2 Members’ Updates...4 Special Articles Modernities Through Art and Design: Printing Press as a Resource of Examining Penang’s Modernity by Sarena Abdullah...6 Malaysia\u27s New “Culture of Entrepreneurship”: Bumiputera Agendas and Dilemmas by Sarah Kelman...19 Meanings of Traditional Textiles Consumption in Brunei Darussalam by Siti Norkhalbi Haji Wahsalfelah...27 Book Reviews....40https://ohioopen.library.ohio.edu/berita/1038/thumbnail.jp

Berita Autumn 2014

Table of Contents Chair’s Address ... 2 Editor’s Foreword...4 Members’ Updates...5 Prizes ... 8 Announcements...10 Malaysian Chinese Muslims in Search of an Identity...11 Brunei’s Syariah Penal Code and Secular Fundamentalism...14 A comparative analysis of online and print media during the 2013 Malaysian General Election: A Research Note...22 Book Review...36 Obituary...39https://ohioopen.library.ohio.edu/berita/1036/thumbnail.jp

Effectiveness of the Influenza Vaccine in Preventing Hospitalizations of Patients with Influenza Community-Acquired Pneumonia

Introduction: Influenza vaccination is the primary strategy for prevention of influenza infection. Influenza infection can vary from mild or even asymptomatic illness to severe community-acquired pneumonia (CAP). Although many national and international investigators and organizations report annual estimates of influenza vaccine effectiveness for prevention of influenza infection in the community, few studies report estimates for the prevention of hospitalizations due to influenza CAP, the most severe form of the infection. The objective of this study is to determine the effectiveness of the influenza vaccine for prevention of hospitalization in patients with influenza-associated CAP. Methods: This was a test-negative study using data from the first two years of the University of Louisville Pneumonia Study, a prospective, observational study of all hospitalized patients with pneumonia in Louisville, Kentucky from 6/1/2014 – 5/31/2016. Univariate and multivariate logistic models were used to evaluate the association between vaccine status and influenza-associated/non-influenza-associated CAP hospitalization. Unadjusted and adjusted vaccine effectiveness estimates were calculated. Results: A total of 1951 hospitalized patients with CAP were included in the analysis, and 831 (43%) reported having received the influenza vaccination for the influenza season by the time they were hospitalized. A total of 152 (8%) cases of influenza-CAP were confirmed in the study population, with 63 (8%) cases confirmed in vaccinated individuals. The unadjusted vaccine effectiveness was not significant, with a point estimate of 5% (95% CI: -33%, 32%). After adjusting for potential cofounders, vaccine effectiveness was also found to not be significant with a point estimate of 8% (95% CI: -30%, 35%). Conclusions: In conclusion, we found that, over the 2014/2015 and 2015/2016 influenza seasons, influenza vaccine was not effective for prevention of hospitalization with CAP due to influenza. More effective vaccines are necessary to prevent the most serious forms of influenza

DNA Testing Reveals the Putative Identity of JB55, a 19th Century Vampire Buried in Griswold, Connecticut

In 1990 in Griswold, Connecticut, archaeologists excavated a burial found in a "skull and crossbones" orientation. The lid of the 19th century coffin had brass tacks that spelled "JB55", the initials of the person lying there and age at death. JB55 had evidence of chronic pulmonary infection, perhaps tuberculosis. It is possible that JB55 was deemed a vampire due to his disease, and therefore had to be "killed" by mutilating his corpse. In an attempt to reveal the identity of JB55, DNA testing was performed. Ancestry informative single nucleotide polymorphism (SNP) analysis using the Precision ID Ancestry Panel indicated European ancestry. A full Y-chromosomal short tandem repeat (Y-STR) profile was obtained, belonging to haplogroup R1b. When the Y-STR profile was searched in the publicly accessible FamilyTreeDNA R1b Project website, the two closest matches had the surname "Barber". A search of historical records led to a death notice mentioning John Barber, whose son Nathan Barber was buried in Griswold in 1826. The description of Nathan Barber closely fits the burial of "NB13," found near JB55. By applying modern forensic DNA tools to a historical mystery, the identity of JB55 as John Barber, the 19th century Connecticut vampire, has been revealed

Germline DDX41 mutations cause ineffective hematopoiesis and myelodysplasia

DDX41 mutations are the most common germline alterations in adult myelodysplastic syndromes (MDSs). The majority of affected individuals harbor germline monoallelic frameshift DDX41 mutations and subsequently acquire somatic mutations in their other DDX41 allele, typically missense R525H. Hematopoietic progenitor cells (HPCs) with biallelic frameshift and R525H mutations undergo cell cycle arrest and apoptosis, causing bone marrow failure in mice. Mechanistically, DDX41 is essential for small nucleolar RNA (snoRNA) processing, ribosome assembly, and protein synthesis. Although monoallelic DDX41 mutations do not affect hematopoiesis in young mice, a subset of aged mice develops features of MDS. Biallelic mutations in DDX41 are observed at a low frequency in non-dominant hematopoietic stem cell clones in bone marrow (BM) from individuals with MDS. Mice chimeric for monoallelic DDX41 mutant BM cells and a minor population of biallelic mutant BM cells develop hematopoietic defects at a younger age, suggesting that biallelic DDX41 mutant cells are disease modifying in the context of monoallelic DDX41 mutant BM

Current Murine Models and New Developments in H3K27M Diffuse Midline Gliomas

Diffuse Midline Gliomas with Histone 3-Lysine-27-Methionine (H3K27M) mutation constitute the majority of Diffuse Intrinsic Pontine Glioma (DIPG), which is the most aggressive form of pediatric glioma with a dire prognosis. DIPG are lethal tumors found in younger children with a median survival <1 year from diagnosis. Discovery of the characteristic H3K27M mutations offers opportunity and hope for development of targeted therapies for this deadly disease. The H3K27M mutation, likely through epigenetic alterations in specific H3 lysine trimethylation levels and subsequent gene expression, plays a significant role in pathogenesis of DIPG. Animal models accurately depicting molecular characteristics of H3K27M DIPG are important to elucidate underlying pathologic events and for preclinical drug evaluation. Here we review the past and present DIPG models and describe our efforts developing patient derived cell lines and xenografts from pretreated surgical specimens. Pre-treated surgical samples retain the characteristic genomic and phenotypic hallmarks of DIPG and establish orthotopic tumors in the mouse brainstem that recapitulate radiographic and morphological features of the original human DIPG tumor. These models that contain the H3K27M mutation constitute a valuable tool to further study this devastating disease and ultimately may uncover novel therapeutic vulnerabilities

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

THE NANOGRAV NINE-YEAR DATA SET: LIMITS ON THE ISOTROPIC STOCHASTIC GRAVITATIONAL WAVE BACKGROUND

We compute upper limits on the nanohertz-frequency isotropic stochastic gravitational wave background (GWB) using the 9 year data set from the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) collaboration. Well-tested Bayesian techniques are used to set upper limits on the dimensionless strain amplitude (at a frequency of 1 yr-1) for a GWB from supermassive black hole binaries of Agw \u3c 1.5 × 10-15. We also parameterize the GWB spectrum with a broken power-law model by placing priors on the strain amplitude derived from simulations of Sesana and McWilliams et al. Using Bayesian model selection we find that the data favor a broken power law to a pure power law with odds ratios of 2.2 and 22 to one for the Sesana and McWilliams prior models, respectively. Using the broken power-law analysis we construct posterior distributions on environmental factors that drive the binary to the GW-driven regime including the stellar mass density for stellar-scattering, mass accretion rate for circumbinary disk interaction, and orbital eccentricity for eccentric binaries, marking the first time that the shape of the GWB spectrum has been used to make astrophysical inferences. Returning to a power-law model, we place stringent limits on the energy density of relic GWs, Ωgw(f)h2 \u3c 4.2 × 10-10. Our limit on the cosmic string GWB, Ωgw(f)h2 \u3c 2.2 × 10-10, translates to a conservative limit on the cosmic string tension with Gμ \u3c 3.3 × 10-8, a factor of four better than the joint Planck and high-l cosmic microwave background data from other experiments