Framing Korean Complex–Coda Resolution with Optimality Theory

Fonotaktika korejskog jezika ne dozvoljava složenu kodu, dakle korejski jezik rabi dvije strategije kako bi razbio suglasničke skupine i prilagodio se tom stanju. Prva je strategija ponovno povezivanje – “relinking” (termin koji rabe Choo&O’Grady 2003:58–9), tj. realizacija suglasničke skupine preko granice sloga, a druga je strategija brisanje. Teorija optimalnosti pogodna je da se njome objasni način na koji se rabe ove dvije strategije, što je ujedno i tema ovoga rada. Koristeći se već ustanovljenim ograničenjima, ovaj rad nadopunjuje istraživanja unutar teorije optimalnosti o sličnim fonološkim procesima u korejskome tako da se navedeni procesi mogu ujediniti pod jednim rangiranjem ograničenja.Korean phonotactics prohibits complex codas; therefore, the language employs two strategies that allow for the breakup of consonant clusters to conform to this prohibition. These strategies include “relinking” (as used by Choo & O’Grady 2003:58–9), that is, the realization of consonant clusters across syllable boundaries, and deletion. The preference of these strategies fits into an Optimality–Theoretic framework, which this paper explicates. By using well established constraints, this analysis complements OT research on similar phonological processes in Korean so that these processes can be unified under a single constraint ranking

Matrix Metalloproteinase 1: Role in Sarcoma Biology

In carcinomas stromal cells participate in cancer progression by producing proteases such as MMPs. The expression MMP1 is a prognostic factor in human chondrosarcoma, however the role in tumor progression is unknown. Laser capture microdissection and In Situ hybridization were used to determine cellular origin of MMP1 in human sarcomas. A xenogenic model of tumor progression was then used and mice were divided in two groups: each harboring either the control or a stably MMP1 silenced cell line. Animals were sacrificed; the neovascularization, primary tumor volumes, and metastatic burden were assessed. LCM and RNA-ISH analysis revealed MMP1 expression was predominantly localized to the tumor cells in all samples of sarcoma (p = 0.05). The percentage lung metastatic volume at 5 weeks (p = 0.08) and number of spontaneous deaths secondary to systemic tumor burden were lower in MMP1 silenced cell bearing mice. Interestingly, this group also demonstrated a larger primary tumor size (p<0.04) and increased angiogenesis (p<0.01). These findings were found to be consistent when experiment was repeated using a second independent MMP1 silencing sequence. Prior clinical trials employing MMP1 inhibitors failed because of a poor understanding of the role of MMPs in tumor progression. The current findings indicating tumor cell production of MMP1 by sarcoma cells is novel and highlights the fundamental differences in MMP biology between carcinomas and sarcomas. The results also emphasize the complex roles of MMP in tumor progression of sarcomas. Not only does metastasis seem to be affected by MMP1 silencing, but also local tumor growth and angiogenesis are affected inversely

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges