A computer-assisted pproach to the comparison of mainland southeast Asian languages

This cumulative thesis is based on three separate projects based on a computer-assisted language comparison (CALC) framework to address common obstacles to studying the history of Mainland Southeast Asian (MSEA) languages, such as sparse and non-standardized lexical data, as well as an inadequate method of cognate judgments, and to provide caveats to scholars who will use Bayesian phylogenetic analysis. The first project provides a format that standardizes the sound inventories, regulates language labels, and clarifies lexical items. This standardized format allows us to merge various forms of raw data. The format also summarizes information to assist linguists in researching the relatedness among words and inferring relationships among languages. The second project focuses on increasing the transparency of lexical data and cognate judg- ments with regard to compound words. The method enables the annotation of each part of a word with semantic meanings and syntactic features. In addition, four different conversion methods were developed to convert morpheme cognates into word cognates for input into the Bayesian phylogenetic analysis. The third project applies the methods used in the first project to create a workflow by merging linguistic data sets and inferring a language tree using a Bayesian phylogenetic algorithm. Further- more, the project addresses the importance of integrating cross-disciplinary studies into historical linguistic research. Finally, the methods we proposed for managing lexical data for MSEA languages are discussed and summarized in six perspectives. The work can be seen as a milestone in reconstructing human prehistory in an area that has high linguistic and cultural diversity

Annotating Cognates in Phylogenetic Studies of South-East Asian Languages [version 2]

Compounding and derivation are frequent in many language families. As a consequence, words in different languages are often only partially cognate, sharing only a few but not all morphemes. While partial cognates do not constitute a problem for the phonological reconstruction of individual morphemes, they are problematic when it comes to phylogenetic reconstruction based on comparative wordlists. Here, we review the current practice of preparing cognate-coded wordlists and develop new approaches that make the process of cognate annotation more transparent. Comparing four methods by which partial cognate judgments can be converted to cognate judgments for whole words on a newly annotated dataset of 19 Chinese dialect varieties, we find that the choice of the conversion method has an impact on the inferred tree topologies that cannot be ignored. We conclude that scholars should take cognate judgments in languages in which compounding and derivation are frequent with great care and recommend to assign cognates always transparently

Annotating Cognates in Phylogenetic Studies of South-East Asian Languages

Compounding and derivation are frequent in South-East Asian languages. Consequently, words in different languages are often only partially cognate, sharing only a few but not all morphemes. While partial cognates do not constitute a problem for the phonological reconstruction of individual morphemes, they are problematic when it comes to phylogenetic reconstruction based on comparative wordlists. Here, we review the current practice of preparing cognate-coded wordlists and develop new approaches that make the process of cognate annotation more transparent. Comparing four methods by which partial cognate judgments can be converted to cognate judgments for whole words on a newly annotated dataset of 19 Chinese dialect varieties, we find that the choice of the conversion method has a large impact on the inferred tree topologies. We conclude that scholars should take cognate judgments in languages in which compounding and derivation are frequent with great care, and recommend to assign cognates always transparently

Computer-Assisted Language Comparison: State of the ArtW

Historical language comparison opens windows onto a human past, long before the availability of written records. Since traditional language comparison within the framework of the comparative method is largely based on manual data comparison, requiring the meticulous sifting through dictionaries, word lists, and grammars, the framework is difficult to apply, especially in times where more and more data have become available in digital form. Unfortunately, it is not possible to simply automate the process of historical language comparison, not only because computational solutions lag behind human judgments in historical linguistics, but also because they lack the flexibility that would allow them to integrate various types of information from various kinds of sources. A more promising approach is to integrate computational and classical approaches within a computer-assisted framework, “neither completely computer-driven nor ignorant of the assistance computers afford” [1, p. 4]. In this paper, we will illustrate what we consider the current state of the art of computer-assisted language comparison by presenting a workflow that starts with raw data and leads up to a stage where sound correspondence patterns across multiple languages have been identified and can be readily presented, inspected, and discussed. We illustrate this workflow with the help of a newly prepared dataset on Hmong-Mien languages. Our illustration is accompanied by Python code and instructions on how to use additional web-based tools we developed so that users can apply our workflow for their own purposes

Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2−/− MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed

Computer-Assisted Language Comparison: State of the Art

Historical language comparison opens windows onto a human past, long before the availability of written records. Since traditional language comparison within the framework of the comparative method is largely based on manual data comparison, requiring the meticulous sifting through dictionaries, word lists, and grammars, the framework is difficult to apply, especially in times where more and more data have become available in digital form. Unfortunately, it is not possible to simply automate the process of historical language comparison, not only because computational solutions lag behind human judgments in historical linguistics, but also because they lack the flexibility that would allow them to integrate various types of information from various kinds of sources. A more promising approach is to integrate computational and classical approaches within a computer-assisted framework, “neither completely computer-driven nor ignorant of the assistance computers afford” [1, p. 4]. In this paper, we will illustrate what we consider the current state of the art of computer-assisted language comparison by presenting a workflow that starts with raw data and leads up to a stage where sound correspondence patterns across multiple languages have been identified and can be readily presented, inspected, and discussed. We illustrate this workflow with the help of a newly prepared dataset on Hmong-Mien languages. Our illustration is accompanied by Python code and instructions on how to use additional web-based tools we developed so that users can apply our workflow for their own purposes

Effects of Ca2+-Activated Cl- Channel ANO1inhibitors on Pacemaker Activity in Interstitial Cells of Cajal

Background/Aims: Anoctamin1 (Ca2+-activated Cl- channel, ANO1) is a specific marker of the interstitial cells of Cajal (ICC) in the gastrointestinal tract, and are candidate proteins that can function as pacemaker channels. Recently, novel selective ANO1 inhibitors were discovered and used to study Ca2+-activated Cl- channels. Therefore, to investigate whether ANO1 channels function as pacemaker channels, selective ANO1 inhibitors were tested with respect to the pacemaker potentials in ICC. Methods: Whole-cell patch-clamp recording, RT-PCR, and intracellular Ca2+ ([Ca2+]i) imaging were performed in cultured ICC obtained from mice. Results: Though CaCCinh-A01 (5 µM), T16Ainh-A01 (5 µM), and MONNA (5 µM) (selective ANO1 inhibitors) blocked the generation of pacemaker potentials in colonic ICC, they did not do so in small intestinal ICC. Though nifulmic acid (10 µM) and DIDS (10 µM) (classical Ca2+-activated Cl- channel inhibitors) also had no effect in small intestinal ICC, they suppressed the generation of pacemaker potentials in colonic ICC. In addition, knockdown of ANO1 reduced the pacemaker potential frequency in colonic ICC alone. Though ANO1 inhibitors suppressed [Ca2+]i oscillations in colonic ICC, they did not do so in small intestinal ICC. T-type Ca2+ channels were expressed in the both the small intestinal and colonic ICC, but mibefradil (5 µM) and NiCl2 (30 µM) (T-type Ca2+ channel inhibitors) inhibited the generation of pacemaker potentials in colonic ICC alone. Conclusion: These results indicate that though ANO1 and T-type Ca2+ channels participate in generating pacemaker potentials in colonic ICC, they do not do so in small intestinal ICC. Therefore, the mechanisms underlying pacemaking in ICC might be different in the small intestine and the colon

Detecting T-cell Reactivity to Whole Cell Vaccines

BCR-ABL$^+$ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown