Post-Apocalyptic Geographies and Structural Appropriation

Excerpt from Routledge Companion to Transnational American Studies, edited by Nina Morgan, Alfred Hornung, and Takayuki Tatsum

Social globalization and design innovation

While designs play a critical role in corporate innovation and business operations, the determinants of design innovation (i.e., new aesthetic or stylistic forms) are largely underexplored in the literature. Accumulating evidence suggests that openness to the exchange of ideas, the adoption of progressive policies, and the circulation of human capital play significant roles in driving regional innovative activities. In this study, we ask a variation of this question: Is there evidence that social globalization, i.e., “the spread of ideas, information, images and people” (Dreher et al., 2008, p. 43) – can drive the extent of national design innovation? We leverage a survey instrument reporting on globalization levels, the KOF Globalization Index, to measure national levels of social globalization. We find that national levels of social globalization predict design innovation, as measured by the number of annual design awards granted by the Industrie Forum (iF) over the period 1973-2015. To address the potential endogeneity in our analysis, we instrument for social globalization using a differences-in-differences approach and an instrumental variable approach. Our findings remain robust when we use U.S. design patents as an alternative measure for design innovation. We further show that personal contact could be the main underlying mechanism for social globalization to encourage design innovation.Othe

Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory.</p> <p>Results</p> <p>We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence <it>in situ </it>hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (< 10 Mb), were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new CNAs in 14/30 (47%) patients, including 28 submicroscopic or hidden aberrations verified by FISH studies. Cryptic 344-kb <it>RUNX1 </it>deletions were found in three patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1, 5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced translocation (n = 1) and low-level clonality (n = 4) in five karyotypically aberrant samples, revealing clinically important assay limitations.</p> <p>Conclusions</p> <p>The detection of previously known and unknown genomic alterations suggests that aCGH has considerable promise for identification of both recurring microscopic and submicroscopic genomic imbalances that contribute to myeloid disease pathogenesis and progression. These findings suggest that development of higher-resolution microarray platforms could improve karyotyping in clinical practice.</p

Testing the predictive ability of technical analysis using a new stepwise test without data snooping bias

In the finance literature, statistical inferences for large-scale testing problems usually suffer from data snooping bias. In this paper we extend the "superior predictive ability" (SPA) test of Hansen (2005, JBES) to a stepwise SPA test that can identify predictive models without potential data snooping bias. It is shown analytically and by simulations that the stepwise SPA test is more powerful than the stepwise Reality Check test of Romano and Wolf (2005, Econometrica). We then apply the proposed test to examine the predictive ability of technical trading rules based on the data of growth and emerging market indices and their exchange traded funds (ETFs). It is found that technical trading rules have significant predictive power for these markets, yet such evidence weakens after the ETFs are introduced. © 2009.preprin

Chinese hamster ovary cells can produce galactose-α-1,3-galactose antigens on proteins

Chinese hamster ovary (CHO) cells are widely used for the manufacture of biotherapeutics, in part because of their ability to produce proteins with desirable properties, including 'human-like' glycosylation profiles. For biotherapeutics production, control of glycosylation is critical because it has a profound effect on protein function, including half-life and efficacy. Additionally, specific glycan structures may adversely affect their safety profile. For example, the terminal galactose-α-1,3-galactose (α-Gal) antigen can react with circulating anti α-Gal antibodies present in most individuals. It is now understood that murine cell lines, such as SP2 or NSO, typical manufacturing cell lines for biotherapeutics, contain the necessary biosynthetic machinery to produce proteins containing α-Gal epitopes. Furthermore, the majority of adverse clinical events associated with an induced IgE-mediated anaphylaxis response in patients treated with the commercial antibody Erbitux (cetuximab) manufactured in a murine myeloma cell line have been attributed to the presence of the α-Gal moiety. Even so, it is generally accepted that CHO cells lack the biosynthetic machinery to synthesize glycoproteins with α-Gal antigens. Contrary to this assumption, we report here the identification of the CHO ortholog of N-acetyllactosaminide 3-α-galactosyltransferase-1, which is responsible for the synthesis of the α-Gal epitope. We find that the enzyme product of this CHO gene is active and that glycosylated protein products produced in CHO contain the signature α-Gal antigen because of the action of this enzyme. Furthermore, characterizing the commercial therapeutic protein abatacept (Orencia) manufactured in CHO cell lines, we also identified the presence of α-Gal. Finally, we find that the presence of the α-Gal epitope likely arises during clonal selection because different subclonal populations from the same parental cell line differ in their expression of this gene. Although the specific levels of α-Gal required to trigger anaphylaxis reactions are not known and are likely product specific, the fact that humans contain high levels of circulating anti-α-Gal antibodies suggests that minimizing (or at least controlling) the levels of these epitopes during biotherapeutics development may be beneficial to patients. Furthermore, the approaches described here to monitor α-Gal levels may prove useful in industry for the surveillance and control of α-Gal levels during protein manufacture.National Center for Research Resources (U.S.) (Grant P41 RR018501-01

SR4GN: A Species Recognition Software Tool for Gene Normalization

As suggested in recent studies, species recognition and disambiguation is one of the most critical and challenging steps in many downstream text-mining applications such as the gene normalization task and protein-protein interaction extraction. We report SR4GN: an open source tool for species recognition and disambiguation in biomedical text. In addition to the species detection function in existing tools, SR4GN is optimized for the Gene Normalization task. As such it is developed to link detected species with corresponding gene mentions in a document. SR4GN achieves 85.42% in accuracy and compares favorably to the other state-of-the-art techniques in benchmark experiments. Finally, SR4GN is implemented as a standalone software tool, thus making it convenient and robust for use in many text-mining applications. SR4GN can be downloaded at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/SR4G

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.Bloodwise, CRUK, MRC, Wellcome Trust, NIH, Leukemia and Lymphoma Societ

Male Germ Cell-Specific RNA Binding Protein RBMY: A New Oncogene Explaining Male Predominance in Liver Cancer

Male gender is a risk factor for the development of hepatocellular carcinoma (HCC) but the mechanisms are not fully understood. The RNA binding motif gene on the Y chromosome (RBMY), encoding a male germ cell-specific RNA splicing regulator during spermatogenesis, is aberrantly activated in human male liver cancers. This study investigated the in vitro oncogenic effect and the possible mechanism of RBMY in human hepatoma cell line HepG2 and its in vivo effect with regards to the livers of human and transgenic mice. RBMY expression in HepG2 cells was knocked down by RNA interference and the cancer cell phenotype was characterized by soft-agar colony formation and sensitivity to hydrogen-peroxide-induced apoptosis. The results revealed that RBMY knockdown reduced the transformation and anti-apoptotic efficiency of HepG2 cells. The expression of RBMY, androgen receptor (AR) and its inhibitory variant AR45, AR-targeted genes insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) was analyzed by quantitative RT-PCR. Up-regulation of AR45 variant and reduction of IGF-1 and IGFBP-3 expression was only detected in RBMY knockdown cells. Moreover, RBMY positive human male HCC expressed lower level of AR45 as compared to RBMY negative HCC tissues. The oncogenic properties of RBMY were further assessed in a transgenic mouse model. Liver-specific RBMY transgenic mice developed hepatic pre-cancerous lesions, adenoma, and HCC. RBMY also accelerated chemical carcinogen-induced hepatocarcinogenesis in transgenic mice. Collectively, these findings suggest that Y chromosome-specific RBMY is likely involved in the regulation of androgen receptor activity and contributes to male predominance of HCC

The gene normalization task in BioCreative III

BACKGROUND: We report the Gene Normalization (GN) challenge in BioCreative III where participating teams were asked to return a ranked list of identifiers of the genes detected in full-text articles. For training, 32 fully and 500 partially annotated articles were prepared. A total of 507 articles were selected as the test set. Due to the high annotation cost, it was not feasible to obtain gold-standard human annotations for all test articles. Instead, we developed an Expectation Maximization (EM) algorithm approach for choosing a small number of test articles for manual annotation that were most capable of differentiating team performance. Moreover, the same algorithm was subsequently used for inferring ground truth based solely on team submissions. We report team performance on both gold standard and inferred ground truth using a newly proposed metric called Threshold Average Precision (TAP-k). RESULTS: We received a total of 37 runs from 14 different teams for the task. When evaluated using the gold-standard annotations of the 50 articles, the highest TAP-k scores were 0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20), respectively. Higher TAP-k scores of 0.4916 (k=5, 10, 20) were observed when evaluated using the inferred ground truth over the full test set. When combining team results using machine learning, the best composite system achieved TAP-k scores of 0.3707 (k=5), 0.4311 (k=10), and 0.4477 (k=20) on the gold standard, representing improvements of 12.4%, 21.8%, and 26.6% over the best team results, respectively. CONCLUSIONS: By using full text and being species non-specific, the GN task in BioCreative III has moved closer to a real literature curation task than similar tasks in the past and presents additional challenges for the text mining community, as revealed in the overall team results. By evaluating teams using the gold standard, we show that the EM algorithm allows team submissions to be differentiated while keeping the manual annotation effort feasible. Using the inferred ground truth we show measures of comparative performance between teams. Finally, by comparing team rankings on gold standard vs. inferred ground truth, we further demonstrate that the inferred ground truth is as effective as the gold standard for detecting good team performance