Characteristics of Regular Functions Defined on a Semicommutative Subalgebra of 4-Dimensional Complex Matrix Algebra

In this paper, we give an extended quaternion as a matrix form involving complex components. We introduce a semicommutative subalgebra ℂ ℂ 2 of the complex matrix algebra M 4 , ℂ . We exhibit regular functions defined on a domain in ℂ 4 but taking values in ℂ ℂ 2 . By using the characteristics of these regular functions, we propose the corresponding Cauchy–Riemann equations. In addition, we demonstrate several properties of these regular functions using these novel Cauchy–Riemann equations. Mathematical Subject Classification is 32G35, 32W50, 32A99, and 11E88.

“That is Why I am Telling this Story”: Musical Analysis as Insight into the Transmission of Knowledge and Performance Practice of a Wapurtarli Song by Warlpiri Women from Yuendumu, Central Australia

Insights into the knowledge, performance, and transmission of songs are pivotal in ensuring the survival of traditional Aboriginal songs. We present the first in-depth musical analysis of a Wapurtarli yawulyu song set sung by Warlpiri women from Yuendumu, Central Australia, recorded in December 2006 with a solo lead singer accompanied by a small group. Our musical analysis reveals that there are various interlocking parts of a song, and this can make it difficult for current generations to learn songs. The context of musical endangerment and the musical analyses presented in our study show that contemporary spaces for learning yawulyu must consider the complex components that come together for a song set to be properly performed.

Inherited Blood Cancer Predisposition through Altered Transcription Elongation

Despite considerable advances in defining the somatic driver mutations underlying myeloid malignancies, including the myeloproliferative neoplasms (MPNs), a significant heritable component for these diseases remains poorly understood. While common genetic variant association studies have been valuable, they fail to explain the majority of heritable variation. We reasoned that rare variant association studies could provide a valuable complementary approach to identify additional inherited risk factors. We therefore utilized exome sequencing data from 166,953 UK Biobank participants and performed a gene-based burden analysis for germline genetic variants conferring risk for acquiring a myeloid malignancy. CTR9, which encodes a key component of the PAF1 transcription elongation complex, was among the significant genes identified (SKAT-O p-value = 5.47x10 -7). The deleterious variants in CTR9 collectively exhibit a 9.6 (95%CI = 4.86-19.04) increased odds of acquiring a myeloid malignancy and this risk was largely driven by the MPNs. We replicated this association in an independent cohort of 211 MPN patients using external controls. We could show through structural and biochemical analyses that the identified deleterious variants perturbed assembly of the PAF1 complex but did not display dominant negative activity. Given that increased hematopoietic stem cell (HSC) self-renewal has been shown to predispose to the risk of acquiring MPNs, we sought to define whether CTR9 perturbation could alter HSC self-renewal or function. We achieved predominantly heterozygous loss-of-function in human hematopoietic stem and progenitor cells (HSPCs) by titrating Cas9 ribonucleoprotein delivery with several independent guide RNAs. Partial loss of CTR9 in HSPCs resulted in expansion of phenotypic long-term HSCs (LT-HSCs) and more differentiated short-term HSCs (ST-HSCs). We additionally could show through single cell RNA-sequencing (scRNA-seq) that there was an expansion of molecularly defined HSCs upon partial loss of CTR9. The observed increase in HSCs appeared paradoxical, given that the PAF1 complex has been suggested to be crucial for HSC maintenance. To explore how the observed HSC expansion with CTR9 perturbation may arise, as well as given known interactions between the PAF1 complex and the competing transcriptional super elongation complex (SEC), we examined whether SEC target genes in HSCs, such as mid to posterior HOXA genes, may be activated with partial CTR9 loss. Remarkably, we observed a significant enrichment for hematopoietic SEC target genes upon CTR9 perturbation in HSCs by gene set enrichment analysis (normalized enrichment score = 3.29, p-value < 0.001). In light of these findings suggesting that SEC activity may be increased with partial CTR9 loss-of-function, as occurs in individuals harboring myeloid malignancy variants, we sought to functionally validate these observations. Using the inhibitors of the SEC, including SR-0813 that targets MLLT3 or with an inhibitor of CDK9, we noted rescue of the CTR9-mediated expansion of phenotypic LT- and ST-HSCs without a significant impact on the bulk HSPC population. To further elucidate underlying mechanisms, we performed immunoprecipitation of PAF1 or SEC component MLLT3 in HSPCs with control or CTR9 editing. While we continued to pull down all PAF1 complex components with PAF1, we also noted pulldown of MLLT3, which increased with CTR9 editing. MLLT3 immunoprecipitation revealed selective pulldowns of PAF1 and CDC73, which also increased with CTR9 editing. These findings show how PAF1 complex components PAF1 and CDC73 interact with and stimulate SEC activity. Our findings reveal how CTR9 usually restricts this activity and constrains transcriptional elongation to limit HSC self-renewal. We functionally validated these findings through selective editing of different PAF1 complex components in HSPCs: we observed reduced HSCs upon editing of PAF1 and CDC73, but increases with editing of other PAF1 complex components. Our findings collectively demonstrate a mechanism by which a previously undefined myeloid malignancy predisposition occurs. We demonstrate that CTR9 loss-of-function stimulates SEC activity and thereby results in HSC expansion to confer risk for acquiring MPNs and other myeloid malignancies. Disclosures Armstrong: Neomorph Inc: Consultancy, Current holder of individual stocks in a privately-held company; Imago Biosciences: Consultancy; Vitae/Allergan Pharma: Consultancy; Cyteir Therapeutics: Consultancy; C4 Therapeutics: Consultancy; OxStem Oncology: Consultancy; Accent Therapeutics: Consultancy; Mana Therapeutics: Consultancy; Janssen: Research Funding; Novartis: Research Funding; Syndax: Research Funding; AstraZeneca: Research Funding. Sankaran: Ensoma: Consultancy; Forma: Consultancy; Cellarity: Consultancy; Novartis: Consultancy; Branch Biosciences: Consultancy.

Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence

Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, in response to a variety of intrinsic and extrinsic stimuli. Although senescence is largely established and maintained by the p53/p21WAF1/CIP1 and pRB/p16INK4A tumour suppressor pathways, the downstream targets responsible for the stability of the growth arrest are not known. We have employed a stable senescence bypass assay in conditionally immortalised human breast fibroblasts (CL3EcoR) to investigate the role of the DREAM complex and its associated components in senescence. DREAM is a multi-subunit complex comprised of the MuvB core, containing LIN9, LIN37, LIN52, LIN54, and RBBP4, that when bound to p130, an RB1 like protein, and E2F4 inhibits cell cycle-dependent gene expression thereby arresting cell division. Phosphorylation of LIN52 at Serine 28 is required for DREAM assembly. Re-entry into the cell cycle upon phosphorylation of p130 leads to disruption of the DREAM complex and the MuvB core, associating initially to B-MYB and later to FOXM1 to form MMB and MMB-FOXM1 complexes respectively. Here we report that simultaneous expression of MMB-FOXM1 complex components efficiently bypasses senescence with LIN52, B-MYB, and FOXM1 as the crucial components. Moreover, bypass of senescence requires non-phosphorylated LIN52 that disrupts the DREAM complex, thereby indicating a central role for assembly of the DREAM complex in senescence.

An Overview of Underwater Connectors

Underwater connectors are very essential and complex components of deep-sea engineering equipment and their design and manufacture have apparent multidisciplinary characteristics. Wet-mateable connectors (WMCs) represent the highest level of technology in this field, and only a very few countries in the world can produce WMCs. So, WMCs are likely to be a constraining factor to some maritime powers that might try to achieve breakthroughs in this field, constraining the innovation-driven development of deep-sea equipment. This paper gives a detailed overview of underwater connectors, both electrical and optical. First, the background of underwater connectors is introduced, and then the main available commercial off-the-shelf (COTS) products are described. Next, the new concept of functional units is proposed by the authors to help readers to have a better understanding of underwater connectors. Then, the basic theories of design are introduced according to different functional units, covering the aspects of electrical/optical connection, pressure-balanced oil-filled (PBOF) technology, penetrable self-sealing, aligning and locking structures. Finally, some discussions and conclusions are presented. This paper aims to reveal the secrets of key technologies used in underwater connectors, especially in WMCs.