Causative Markers Research Articles

Causative construction in Likpakpaanl (Konkomba)

This article is a contribution to the cross-linguistic discussion on causation. It proceeds on the note that causation is a significant notion, both cognitively and grammatically. I make a case that the Mabia (Gur) languages of West Africa are severely under-represented in the literature on causation. I then focus on causation in Likpakpaanl, an under-researched Mabia language spoken in Ghana and Togo in West Africa. I further present data from thirteen other related West African languages for comparative purposes. Broadly speaking, Likpakpaanl deploys all the traditional causation strategies- lexical, morphological, serialising and analytic. However, the use of nasals, especially vowel nasality as a causativisers is novel and uniquely places Likpakpaanl among its linguistic relatives. The Likpakpaanl analytic causative marker chà has a functional scope for both factitive and permissive causatives. In a sense, the source of the specialised analytic causative marker in Likpakpaanl diverges from the oft-cited cross-linguistic source of analytic causative markers. The Likpakpaanl biclausal causative is the balanced structure and, therefore, aligns well with the biclausal causative structure described for the West African linguistic area, contra the deraked structure of Indo-European languages. A thorough investigation of the constellation of causatives in Mabia promises new insights into causative typology.

The categorization of causatives in modern Chinese

The article presents a model for applying methods of corpus linguistics to the categorization of causatives that convey semantics of causality in contemporary Chinese. The author employs the core functions of the corpus manager Sketch Engine, including thesaurus, concordance and word list in order to select contextual synonyms, search to find illustrative material and generate lexical units with preset parameters accordingly. Specifically, online corpus of Chinese Web 2017 (zhTenTen17) Simplified, which contains approximately 16.6 billion tokens, was used to conduct the study.Notably, in modern Chinese, the category of causality is primarily realized through causative constructions, which/whose type is determined by the causative predicate. The present paper studies both lexical and grammatical causatives. The results illustrate that lexical causatives include mono- andmulti-component types, while grammatical causatives are divided into those formed by two full verbs; those formed by a full verb and a resultative component; and those formed by a combination of light and non-causative verbs. Besides, grammatical causative constructions are divided into two main subtypes: morphological and analytical. The morphological one conveys semantics of causality either through causative affixes or phonological changes, while the analytical one being the most prevalent in modern Chinese are further classified into three models, namely: those formed with causative markers; those formed with the causative preposition 把; and those formed with the word 得. Future research may focus on the pragmatics of the choice in different types of causative constructions, with a regard to the conceptual and linguistic worldview of the Chinese people.

397 Field Demonstration Analyzing the Implementation of Individual Animal Electronic Identification and Genetic Testing in Western Range Sheep Flocks

Abstract The lack of individual performance records derived from an extensively driven production system coupled with impracticality to utilize reproductive technologies makes commercial genetic improvement challenging in small ruminants. We collaborated with five producers throughout California to assess how Electronic ID (EID) and a genotyping panel can augment the productivity of a flock. We sought to study how the data collected from these technologies can hasten genetic improvement towards desirable operational objectives. Familiarity and use of EID tags on ranches at the start of the research varied; thus, allowing for a qualitative reflection on the perceptions of the participants of the usefulness of this technology. We partnered with Superior Farms, a slaughterhouse, to evaluate their targeted genotyping panel, Flock54. Flock54 is a single nucleotide polymorphism (SNP) panel containing 956 markers for assigning pedigree and includes markers linked to quantitative trait loci and/or known single gene causative markers to aid in disease management and fecundity scoring. Ear notch samples were collected from 2,963 animals for analysis. This included 305 total sires as well as their progeny, 989 female lambs and 1,669 male lambs, which were marketed. Nine lambs were positive at a fecundity marker. No other notable results were found from the Flock54 panel. Genomic data was used to ascertain prolific sires on every ranch; however, ram to ewe ratio altered the influence that a prolific sire had on a lamb crop. The lowest ram to ewe ratio was 1:10. Parentage results from this ranch reports the following progeny metrics: Average: 9.9 males (±12.5); Median: 4 males; Max: 61 males, minimum 1 male. In contrast, the greatest ram to ewe ratio was 1:50. Parentage results from this ranch reports the following progeny metrics: Average: 51.9 (± 41.7); Median: 43.5; Max: 135; Minimum: 4,524 carcass samples from terminal lambs at two ranches were processed at Superior Farms` plant and assessed with a USDA inspected camera grading system. Progeny contemporary group deviations were calculated for hot carcass weight, yield grade, ovine cutability calculation (OCC), and OCC yield. After coupling carcass metrics with USDA reported prices, we identified prolific sires within the flock that garnered significantly higher and lower dollar merit at slaughter. A two-tailed Student`s T-test was used on the dollar deviation of edible product sold to identify if there was a statistically significant difference (P-value < 0.05) between a given ram`s progeny and the rest of the progeny slaughtered. We found that twenty-three out of the forty-three rams with progeny from one ranch had a statistically significant dollar deviation difference with a T-value greater than 2.0167. For the other ranch, we found that nineteen out of the thirty-five rams with progeny had a statistically significant difference with a T-value greater than 2.0301.

Differences in Korean learners’ acquisition of causative expressions: focus on learners’ proficiency level

This study examines the learning patterns of intermediate and advanced Korean learners in the acquisition of causative expressions according to their proficiency and the causative sentence type. We measured their grammatical knowledge using three types of grammaticality judgment tasks (GJTs) and self-paced reading tasks (SPRTs) differing in time limit and modality. We included the GJT A' score and reading time (RT) for SPRTs’ target and spillover regions. The results showed that intermediate learners’ accuracy for morphological and lexical causatives was lower than that for syntactic causatives, while advanced learners’ accuracy for lexical causatives was lower than that for syntactic and morphological causatives. Learners showed a lower accuracy for timed written and aural GJTs than untimed GJT. In SPRT, learners took twice as long to process the target regions as native speakers and even longer to process spillover regions. Advanced learners had a longer RT. Learners had a low correct rate for causative suffix substitution and adjectival root questions, substitution questions on causative markers, and substitution questions on causee case postpositions in morphological, syntactic, and lexical causatives. Learners showed confusion with active sentences in lexical causatives. This study has implications for understanding causative expression acquisition for learners’ proficiency levels.

PSIII-2 Late-Breaking: Collaboration to Demonstrate the Potential Use and Value of Electronic Identification and DNA Testing in the Sheep Industry

Abstract The dearth of individual performance records derived from an extensively driven production system coupled with the impracticality of utilizing reproductive technologies makes commercial genetic improvement challenging in small ruminants. We collaborated with five producers throughout California to assess how electronic ID (EID) and genetic testing could inform ram selection. Our objective was to determine how the data collected from these technologies could augment genetic improvement on commercial ranches. Familiarity and use of EID tags on ranches at the start of the research varied; thus, allowing for a qualitative reflection on the participant's perceptions of the usefulness of this technology. Ear notch samples were collected and EID ear tags were placed in 2,963 sheep; 305 rams, and 2,658 of their potential progeny. We partnered with Superior Farms (Dixon, CA) to genotype the animals using their Flock54 single nucleotide polymorphism panel which contains 956 markers for assigning parentage, and includes markers linked to quantitative trait loci and/or known single gene causative markers to aid in disease management. SNP data was used to assign paternity and determine sire prolificacy. A total of 524 carcass samples from ram lambs from two of the ranches were processed at Superior Farms' plant and assessed with a USDA-approved camera grading system (e+v, Oranienburg, Germany) that matches EID’s to carcass data. Progeny contemporary group deviations were calculated for hot carcass weight, yield grade, and ovine cutability calculation (OCC) which predicts the yield of edible product on the carcass. The average number of lambs per sire born at each ranch and the mean OCC of the progeny for each sire were compared using a one-way analysis of variance. There was a significant ranch effect on the average progeny number per ram (P < 0.05). The ranch with the lowest ram to ewe ratio (1:10) also has the lowest average progeny per ram and the ranch with the greatest ratio (1:50) has the most progeny per ram. There was a large range in the number of lambs per sire (0-135) within each ranch. There was a significant sire effect (P < 0.05) on average OCC within each progeny contemporary group, meaning some sires were producing offspring with significantly more marketable meat. The use of EIDs in combination with genetic testing, allowed for the collection of individual progeny performance data. This provided insight into sire performance and identified prolific sires that were also producing lambs with superior carcass merit. Producers could use this information to select for high-performing rams; however, there is an unavoidable delay between ram turnout and the collection of progeny carcass data. This limits the practical utility of these data and reinforces the value of having estimated breeding values available at ram purchase to select genetically superior rams.

Insight into the Candidate Genes and Enriched Pathways Associated with Height, Length, Length to Height Ratio and Body-Weight of Korean Indigenous Breed, Jindo Dog Using Gene Set Enrichment-Based GWAS Analysis.

Simple SummaryThe height, length and body-weight are the economic traits of Jindo dogs and it is necessary to study their underlying genetic basis. Thus, a post-genome-wide association enrichment study on four body-size traits of Jindo dog including height, length, length to height ratio and body-weight was carried out here. The results revealed several potential single nucleotide polymorphisms (SNPs) and genes which were significantly associated with the traits of interest. Furthermore, we have found several pathways to be significantly associated with the traits of interest and these pathways are generally involved in the growth and development process. The findings of this study may help to use the identified SNPs and genes as possible biomarkers for Jindo breeding.As a companion and hunting dog, height, length, length to height ratio (LHR) and body-weight are the vital economic traits for Jindo dog. Human selection and targeted breeding have produced an extraordinary diversity in these traits. Therefore, the identification of causative markers, genes and pathways that help us to understand the genetic basis of this variability is essential for their selection purposes. Here, we performed a genome-wide association study (GWAS) combined with enrichment analysis on 757 dogs using 118,879 SNPs. The genomic heritability (h2) was 0.33 for height and 0.28 for weight trait in Jindo. At p-value < 5 × 10−5, ten, six, thirteen and eleven SNPs on different chromosomes were significantly associated with height, length, LHR and body-weight traits, respectively. Based on our results, HHIP, LCORL and NCAPG for height, IGFI and FGFR3 for length, DLK1 and EFEMP1 for LHR and PTPN2, IGFI and RASAL2 for weight can be the potential candidate genes because of the significant SNPs located in their intronic or upstream regions. The gene-set enrichment analysis highlighted here nine and seven overlapping significant (p < 0.05) gene ontology (GO) terms and pathways among traits. Interestingly, the highlighted pathways were related to hormone synthesis, secretion and signalling were generally involved in the metabolism, growth and development process. Our data provide an insight into the significant genes and pathways if verified further, which will have a significant effect on the breeding of the Jindo dog’s population.

CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy.

Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK-3β, which results in up-regulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK-3 inhibitor, as a potential drug for use in ES therapy. Our data highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.

CAUSATIVE CONSTRUCTION IN ASAHAN MALAY LANGUAGE: MORPHOLOGICAL CAUSATIVE ANALYSIS

This study attempts to describe morphological causative in Asahan Malay Language (AML). This research employed qualitative approach. This study followed the steps of data collection and data analysis. The data of this research were obtained through field linguistics method which covered direct elicitation, recording, and elicitation checking. The classified data were clarified with the native speakers of this language to improve the reliability of the data. From the analysis, it can be concluded that morphological causative construction in AML implies that the meaning of cause and effect. It is indicated by the use of suffix –kan and -i. In addition, causative markers of –kan and –i in AML can be attached to verbs, adjectives, nouns, and numerals.

Sentences with Object-oriented Adverbials and the Syntax-Semantics Interface

SOOAs refer to the phenomenon that the state adjective in the adverbial position is semantically associated with the object. In this paper this fact will be accounted for by invoking the properties of a pre-syntactic level of semantic representation and its interplay with syntax proper. It will be argued that the object-oriented adverbial is not derived from the attributive; in effect, it is base-generated in the complement position. A model of projection of arguments that allows for this will be proposed. It will be shown that the other special properties of SOOAs follow from the way the verb’s object and complement are represented at the pre-syntactic level. In particular, it will be shown that the underlying structure must satisfy both the requirement of the syntactic system and the requirement of the semantic system. The presence of any symbol in a representation is conditional. The theta-roles of internal arguments are assigned by the predicate, which is locally constrained, whereas the theta-roles of external arguments are assigned by the maximal projection of the predicate, viz. VP. When an external argument occurs, there is an empty predicate position in the representation, for there is an asymmetry between the conceptual system and the syntactic system. Derivation involves Move-α and Generalized Transformation. Different use of derivation methods gives rise to various forms of constructions in Chinese. Similarly, different semantic orientations result from different distributions. The state adjective is base-generated in the position behind the object because its nature is to serve the function of the complement of the object. It co-occurs with the object in the embedded VP because they are closely related to each other in terms of semantics. There is no overt predicate between the object and the state adjective. The state adjective occurs in other positions, which is the result of movement. Movement falls into two types, viz. object movement and state adjective movement. Object movement is prior to state adjective movement. In order to satisfy the requirement of feature checking, the object moves to the position NP. Then the state adjective moves to the major predicate and merges with it so as to maintain its semantic association with the state adjective and to serve the function of the complement. It follows that the difference between Chinese SOOAs and English as well as German SOOAs lies in the distance of movement of state adjectives. In Chinese, there are causative markers, resultative markers, and manner markers that can license the state adjective in the landing sites and help to maintain its semantic association with the object while in English and German there are no such markers. As a consequence, the object in Chinese-type SOOAs does not move while the state adjective moves out of the embedded VP to the empty verb position where the manner marker is inserted. The major predicate moves to the same position and merges with the newly-formed syntactic object ADJ-MANN. Furthermore, Chinese-type SOOAs allow the state adjective to precede the major predicate as the manner marker can license the state adjective. In contrast, in English-type SOOAs, neither the state adjective nor the object moves. Moreover, English-type SOOAs do not allow the state adjective to come before the major predicate because there is no manner marker to license it.

Hittite causative markers in a diachronic Anatolian perspective

Hittite causative markers in a diachronic Anatolian perspective

Genome-wide association study of vitamin E in sweet corn kernels

Vitamin E, consisting of tocopherols and tocotrienols, serves as a lipid-soluble antioxidant in sweet corn kernels, providing nutrients to both plants and humans. Though the key genes involved in the vitamin E biosynthesis pathway have been identified in plants, the genetic architecture of vitamin E content in sweet corn kernels remains largely unclear. In the present study, an association panel of 204 inbred lines of sweet corn was constructed. Seven compounds of vitamin E were quantified in sweet corn kernels at 28 days after pollination. A total of 119 loci for vitamin E were identified using a genome-wide association study based on genotyping by sequencing, and a genetic network of vitamin E was constructed. Candidate genes identified were involved mainly in RNA regulation and protein metabolism. The known gene ZmVTE4, encoding γ-tocopherol methyltransferase, was significantly associated with four traits (α-tocopherol, α-tocotrienol, the α/γ-tocopherol ratio, and the α/γ-tocotrienol ratio). The effects of two causative markers on ZmVTE4 were validated by haplotype analysis. Finally, two elite cultivars (Yuetian 9 and Yuetian 22) with a 4.5-fold increase in the sum of α- and γ-tocopherols were developed by marker-assisted selection, demonstrating the successful biofortification of sweet corn. Three genes (DAHPS, ADT2, and cmu2) involved in chorismate and tyrosine synthesis were significantly associated with the α/γ-tocotrienol ratio. These results shed light on the genetic architecture of vitamin E and may accelerate the nutritional improvement of sweet corn.

Identification of genes associated with reproductive function in dairy cattle.

The use of genomics has improved response to selection for functional traits with low heritability such as fertility traits. Much of the work on fertility traits has been performed through use of genome-wide association studies (GWAS) to identify genetic loci associated with reproductive traits. Under a GWAS approach, the assumption is that the markers on the panel are in linkage disequilibrium with causative mutations. In many cases, identification of the causative mutation is difficult because an associated genetic marker can be in intergenic regions and can be in linkage disequilibrium with variants in several nearby genes. Another approach is to identify candidate genes using knowledge of the biological pathways controlling a trait to search for single nucleotide polymorphism (SNP) in genes in those pathways. This should reveal putative causative markers responsible for genetic variation in biological function, and it is expected that the marker will be more strongly associated with a trait than one in linkage disequilibrium. An example of how a series of candidate gene studies demonstrate that identification of markers in genes involved in reproductive processes can lead to discovery of additional markers associated with genetic variation in reproductive traits is presented. In addition, the inclusion of candidate markers for fertility can improve reliability of genetic estimates for fertility traits, and the repeatability of the effects across a separate population of animals gives confidence that association elucidated by this set of markers is likely to be real. More importantly, the use of candidate genes can provide insights into the biology underpinning genetic variation in fertility, and that this understanding can lead to physiological interventions to improve reproductive function.

Novel genetic loci associated HLA-B*08:01 positive myasthenia gravis

ObjectiveTo identify potential causative markers involved in the development of early-onset myasthenia gravis (EOMG) in the MHC and non-MHC regions that may interact with the HLA-B*08:01 allele. MethodsWe analyzed 583 MG patients and identified 5 patients homozygous for the disease-associated ancestral haplotype 8.1 (HLA-A*01:01, B*08:01, DRB1*03:01, DQB1*02:01). We also analyzed more than 9000 controls and selected 24 for further investigation. We subsequently conducted a fine mapping analysis through high-throughput sequencing of the MHC region (from upstream of the GPα5 gene to downstream of the ZBTB9 gene). For the interaction analysis we analyzed a total of 150,090 SNPs equally distributed throughout the genome in the individuals that were homozygous for the main susceptibility HLA allele HLA-B*08:01 and investigated the expression of the genes located close to the observed susceptibility variants. ResultsThe overall coverage of the 4.79 Mb MHC region ranged between 96.57% and 97.41%. We identified 705 new variants in the MHC region (673 SNPs and 32 InDels). However, no significant differences were found between patients and controls within the MHC region of the ancestral 8.1 haplotype. As the susceptibility gene is considered to be located close to the HLA-B locus, complete sequencing of the surrounding 200 kb was carried out in the 5 patients and 24 controls. No significant differences where observed, suggesting that the HLA-B molecule itself is the susceptibility factor for EOMG.We also observed two new susceptibility loci specific for MG HLA*08:01 patients (P < 3.33 × 10−7). These loci map to an intronic OVCH1 variant (rs10492374; P = 1.90 × 10−8) and a 5′ downstream CNPY2 variant (rs10783780; P = 3.33 × 10−7) on chromosome 12. Individuals heterozygous for GA*rs10492374 showed an increased expression of the OVCH1 gene. The rs10783780 genotypes were not associated with CNPY2 mRNA levels, but the MG HLA*08:01 patients present a lower expression of this gene than the healthy controls. ConclusionOur results showed that when we control for the influence of the ancestral haplotype 8.1, no polymorphism was demonstrated to be associated with EOMG development within the MHC region suggesting that the HLA-B*08:01 allele is the unique genetic factor within the HLA region responsible for EOMG development in patients who carry the ancestral haplotype 8.1. Our study also identified two novel polymorphisms as risk factors for MG HLA-B*08:01 positive patients which regulate the expression of the OVCH1 and CNYP2 genes.

ASPECTUAL AUXILIARY VERBS IN XITSONGA

In Xitsonga, certain Aspectual Auxiliary verbs (AA verbs) appear with double subject agreement. While these AA verbs have been reported in the description of Xitsonga (Baumbach 1987: 250-252), a systematic morphosyntactic study of these constructions has not been undertaken. This study aims to fill this gap. An AA verb is marked with tense, aspect, mood, negation and relative clause markers and may occur in wh-questions. The lexical verb following the AA verb may be the target of verbal extensions (applicative and reciprocal), reflexive, causative and passive markers.

Properties and Modeling of GWAS when Complex Disease Risk Is Due to Non-Complementing, Deleterious Mutations in Genes of Large Effect

Current genome-wide association studies (GWAS) have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE). This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders), and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

Abstract 2259: Identifying causative genes and prognostic markers for bladder cancer

Abstract Upon presentation 70% of the bladder tumors are confined to the epithelial (stage pTa) and stromal layers (stage pT1) of the bladder. These non-muscle invasive tumors (NMI-BC) frequently recur and 10-15% will eventually invade the detrusor muscle and may cause metastases. The management of these tumors is characaterized by the difficult choice between transurethral resection (TURB) or total bladder removal by cystectomy. Our first objective was to identify DNA copy number changes as biomarkers predicting tumor progression in high grade NMI-BC to aid decision making. A set of 18 DNA samples isolated from fresh frozen high grade NMI-BC was hybridized on Illumina SNP arrays. Analysis of alterations was done with Nexus software. Hierarchical clustering of significantly differing SNPs showed that tumors that progressed and those that did not clustered separately. A comparison of the differential alterations between tumor groups resulted in many chromosomal locations encompassing chromosome 1p, 2-6, 8-10, 12p, 13q, 17q, 18p and 22q that were fit for inclusion in a validation assay. A custom Agilent 15K array was designed to include probes for these locations. We collected a retrospective series of 96 high grade NMI-BC paraffin embedded tumors with a median follow-up of 5 years. Half of these samples were from patients who developed a muscle-invasive tumor at a later time. Preliminary results show an interesting region on chromosome 8 with the best independent prognostic value. This region and the genes therein will be studied in more detail. This and other validated regions will be used to design a definitive prognostic assay. Complex losses on chromosome 9 characterize bladder tumors regardless of stage. We hypothesized that the complex rearrangements on this chromosome in BC are the results of attempts of the tumor cell to loose tumor suppressor genes whilst struggling to retain other (onco)genes. Therefore, the second aim was to identify pivotal tumor suppressor and/or oncogenes on chromosome 9 for development of bladder cancer, with the aim to exploit these genes or the pathways in which they function as potential targets for therapy for tumors from all stage categories. A custom Agilent 44K array was designed, containing probes for all genes on chromosome 9 (and 8p). DNA from a series of 144 tumors from different stages was hybridized to the arrays. Analysis of alterations was done with Nexus software. We found many regions of loss as expected but also a region that appeared amplified in most tumors. Several candidate regions were validated of their copy number status with specific MLPA assays. Two potential candidate genes from chromosome 9 were selected for mutational and functional analysis. In one of those genes we found several mutations affecting protein function, suggesting that this gene is a new tumor suppressor gene for bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2259. doi:10.1158/1538-7445.AM2011-2259

Evaluation of random forests performance for genome-wide association studies in the presence of interaction effects

Random forests (RF) is one of a broad class of machine learning methods that are able to deal with large-scale data without model specification, which makes it an attractive method for genome-wide association studies (GWAS). The performance of RF and other association methods in the presence of interactions was evaluated using the simulated data from Genetic Analysis Workshop 16 Problem 3, with knowledge of the major causative markers, risk factors, and their interactions in the simulated traits. There was good power to detect the environmental risk factors using RF, trend tests, or regression analyses but the power to detect the effects of the causal markers was poor for all methods. The causal marker that had an interactive effect with smoking did show moderate evidence of association in the RF and regression analyses, suggesting that RF may perform well at detecting such interactions in larger, more highly powered datasets.

Growing opportunities for adjuvant therapy of renal cell carcinoma: targeted drugs and vaccines

The management of advanced renal cell carcinoma (RCC) is undergoing a revolution, with the introduction of new agents and surgical paradigms. Thoughtful integration of diagnostic, surgical and medical approaches to the patient is paramount for disease control. Methods of risk stratifying kidney cancers are reviewed, as well as mechanisms of action of newer drugs approved in advanced metastatic kidney cancer. These drugs present opportunities for application to patients in an earlier stage of disease, and adjuvant RCC trials designs are discussed. Improvements have been made in the understanding of the molecular and genetic basis of RCC, both for causative and prognostic markers, with models addressing prediction of tumor behavior and therapeutic targets. Practice patterns have shifted from cytokine therapies to targeted molecular approaches, particularly emphasizing the VEGF pathway, related intracellular kinases and the mammalian target of rapamycin. Autologous vaccine adjuvant studies are maturing. In conclusion, elucidation of specific genes, proteins and aberrant molecular pathways associated with kidney cancer are ongoing. These new agents may lead to opportunities to improvement of disease-free survival through therapy in the adjuvant setting.

Verb Classification in Mayrinax Atayal

Verb classes are examined in Mayrinax Atayal, an Austronesian language spoken in Taiwan, based on certain semantic, morphological, and syntactic properties. Focus markers; negative, imperative, and causative constructions; the tense/aspect/mood system of the language; and a dimension of greaterlesser dynamicity (or stativity) are all investigated. The primary distinction between dynamic and stative verbs is supported by the different behaviors of verbs in the various constructions. Because degrees of dynamicity/stativity of Mayrinax verbs are relative rather than absolute, a continuum is proposed with dynamic verbs and stative verbs appearing at the two extremes. 1. INTRODUCTION. Atayal is one of the more widespread of the Formosan languages, ranging from Ban Prefecture in the northeast of Taiwan to Taipei and Taoyuan Prefectures in the north, and southward through Hsinchu, Miaoli, and Taichung Prefectures to Nantou in the central portion of the island. It consists of two major subgroups, namely, Squliq and C?uli?, the latter of which is considered as being more conservative. The dialectal variant examined in this paper is that of Mayrinax, a C?uli? dialect spoken in Chinshui Village, Taian Hsiang, Miaoli Prefecture. Of all Formosan languages and dialects, Mayrinax is one of the only two known dialects that show certain distinctions between the male and female forms of speech; the other dialect is Pa?kuali? (cf. Li 1980). While such distinctions between the male and female speech forms are still preserved in the older generation's speech, younger speakers tend to ignore these differences and mix the two forms in their speech. This paper attempts to examine verb classes in Mayrinax Atayal. To our knowledge, there are four studies [2] that deal primarily with verb classification in certain Formosan languages; namely, Jeng (1981) on Yami, Chen (1987) and Y. Huang (1988) on Amis, and Tseng (1989) on Squliq Atayal. Most of these studies rely heavily on Syntax--case relations, case forms, and distributional properties. In this paper, we attempt to classify Mayrinax verbs on the basis of certain semantic, morphological, and syntactic properties. We first consider how verbs are formed in the language. We then show a primary classification for them, namely, dynamic verbs versus stative verbs. [3] While dynamic verbs designate actions, processes, or situations, stative verbs tend to denote properties, states, or resultant states. We attempt to justify such a classification by examining the semantic dynamicity (or stativity) of Mayrinax verbs, and the morphosyntactic behaviors they exhibit in the focus system, [4] in negative, imperative, a nd causative constructions, and in the tense/aspect/mood system. 2. VERB FORMATION IN MAYRINAX ATAYAL. Languages may have various ways of forming verbs. In this section, we will investigate how verbs are formed in Mayrinax Atayal. The language has words that are inherent verbs. As pointed out by Huang (1995), agent-focus verbs appearing in affirmative imperatives are considered to be basic forms [5] that are also used in agent-focus realis negative declaratives. These verbs can be further affixed with varying focus markers, tense/aspect/mood markers, and/or causative markers, with or without overt affixation, depending on, among other factors, which argument is in focus (e.g., agent, patient, location, instrument; or beneficiary) and what syntactic construction a given verb is being used in (e.g., declarative or imperative, affirmative or negative). In addition to the above-mentioned inherent verbs and their derivatives affixed with different focus, tense/aspect/mood, and/or causative markers, Mayrinax Atayal has verbs whose basic forms are derived from nouns affixed with either a causative marker, a stative marker, a preposition, or a zero-morpheme focus marker, [6] as exemplified in (I-4). [7] (I) Verbs derived from nouns affixed with the causative marker pa-: a. …