99 research outputs found
Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities
The outcomes of patients with multiple myeloma (MM) refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) remain poor. In this study, we performed whole genome and transcriptome sequencing of 39 heavily pretreated relapsed/refractory MM (RRMM) patients to identify mechanisms of resistance and potential therapeutic targets. We observed a high mutational load and indications of increased genomic instability. Recurrently mutated genes in RRMM, which had not been previously reported or only observed at a lower frequency in newly diagnosed MM, included NRAS, BRAF, TP53, SLC4A7, MLLT4, EWSR1, HCFC2, and COPS3. We found multiple genomic regions with bi-allelic events affecting tumor suppressor genes and demonstrated a significant adverse impact of bi-allelic TP53 alterations on survival. With regard to potentially resistance conferring mutations, recurrently mutated gene networks included genes with relevance for PI and IMiD activity; the latter particularly affecting members of the Cereblon and the COP9 signalosome complex. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients; a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies
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Jokes and Riddles
Recording of Laila Khan reciting a series of situational jokes in the Hunza dialect of Burushaski
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Transcription: Retelling of Bilbal Wazir
Transcription of Bano reciting “Bilbal Wazir” in the Hunza dialect. This is a popular story about Minister Bilbal, who was once a worker, and spent his money before he came home t his wife. He then proves his wisdom by not doing what he was told, and became a minister. Transcription is done in Burushaski with translations in English
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Recipes
Recording of Ruqayya sharing a recipe for “Ghulmaldi”, a yoghurt dip made for covering thin bread and butter. This is told in the Nagar dialect
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Photograph of Burushaski speakers
Photograph of Yasin Burushaski poets, musicians and resource person during linguistic field visit by Sadaf Munshi
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Photograph of Burushaski speakers with research team
Photograph of a gathering of Yasin Burushaski speakers during a linguistic field visit while Mr. Piar Karim, research assistant to Dr. Sadaf Munshi, is video-recoding the event
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Jammu and Kashmir Burushaski: language, language contact, and change
textThe region stretching along the Kashmir province of the state of Jammu &
Kashmir in India and the Northern Areas region of Pakistan is home to great ethnolinguistic
diversity. The impetus for conducting a study on the Burushaski language in the
valley of Kashmir came from the realization that the community, although invisible
(roughly 300 speakers) within the broad Kashmiri society (over 4 million speakers), has
succeeded in maintaining a separate identity – social and linguistic. Having lived in
Srinagar for over a century, Jammu & Kashmir Burushos have very well stood the
pressures of linguistic assimilation and language loss. No study has been carried on the
language of the Jammu & Kashmir Burushos so far.
This study provides a structural description of Jammu & Kashmir Burushaski - an
undocumented variety of Burushaski, and analyzes the various forms of linguistic
interference since its split from the parent dialects in Pakistan. It covers the various
linguistic consequences of contact such as: borrowing, innovation, and simplification of
linguistic features characterizing Jammu & Kashmir Burushaski. Changes are studied at
lexical, phonological, and morpho-syntactic level. My synchronic description of the
grammar is concerned with the structural properties of the language. Grammatical
description is preceded by an introduction of various speech forms in context which
emphasizes the importance of a discourse-centered approach followed in this study. My
approach to the study of contact-induced change is based on an analytical framework
following Thomason & Kaufman (1988) and Thomason (2001). The study also discusses
some theoretical implications of the research outcomes. It presents a unique situation in
which linguistic outcomes of contact are reflected via a complex interplay of various
factors involving simultaneous contact with two languages viz., Kashmiri and Urdu, each
affecting the language in a specific way – lexical borrowing from Urdu and structural
borrowing from Kashmiri. This is explained in terms of two important factors: (i)
language ideology in terms of a “native language” versus an “extra-native MATRIX”,
and (ii) within the non-native matrix, a hierarchy of social prestige associated with each
of the two non-native languages.Linguistic
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Personal Narratives and Accounts
Recording of Raja Sakhawat Ali Khan reciting a personal narrative of his family history in the Srinagar dialect. He recalls how his ancestry came to Srinagar. He tells of his fathers, and his brothers and their children, and his own children, and what they work as
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Stories
Recording of Raja Safdar Ali Khan, a retired school teacher, reciting "the Fox and the Rooster," in the Srinagar dialect. This popular story tells of a hungry fox and a boastful rooster, and advises children to be aware of how they speak and act
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Recipes
Recording of Ruqayya Bano sharing a recipe for “Diram Phiti”, or a sweet bread cake, in the Nagar dialect. Grain is germinated, then ground into flour and fermented. This flour is made into dough, and cooked on an iron pan in individual patties
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