Lucia leyba biography of michaels

Published in final edited form as: Cell. Apr 5;(2)–e doi: /

SUMMARY

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression machine learning algorithm (OCLR) to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune system cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.

ETOC

Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveals new drug targets for anti-cancer therapies

INTRODUCTION

Stemness, defined as the potential for self-renewal and differentiation from the cell-of-origin, was originally attributed to normal stem cells that possess the ability to give rise to all cell types in the adult organism. Cancer progression involves gradual loss of differentiated phenotype and acquisition of progenitor-like, stem cell-like features. Undifferentiated primary tumors are more likely to result in cancer cell spread to distant organs, causing disease progression and poor prognosis, particularly because metastases are usually resistant to available therapies (Friedmann-Morvinski and Verm

Italian historical novel

The Betrothed (Italian: I promessi sposiItalian:[iproˈmessiˈspɔːzi]) is an Italian historical novel by Alessandro Manzoni, first published in , in three volumes, and significantly revised and rewritten until the definitive version published between and It has been called the most famous and widely read novel in the Italian language.

Set in the Duchy of Milan in , during the years of Spanish rule, the novel is also noted for its extraordinary description of the plague that struck Milan around

The novel deals with a variety of themes, for example: the illusory nature of political power and the inherent injustice of any legal system; the range of character among the Christian clergy from the cowardice of the parish priest Don Abbondio to the heroic sanctity of others (the friar Padre Cristoforo, the cardinal Federico Borromeo); and the unwavering strength of love (the relationship between Renzo and Lucia, and their struggle to finally meet again and be married). The novel is renowned for offering keen insights into the meanderings of the human mind.

Writing and publication

Manzoni found the basis for his novel in when he read a Italian edict that specified penalties for any priest who refused to perform a marriage when requested to do so. More material for his story came from Giuseppe Ripamonti's Milanese Chronicles.

The first version, Fermo e Lucia, was written between April and September He then heavily revised it, finishing in August ; it was published on 15 June , after two years of corrections and proof-checking. Manzoni's chosen title, Gli sposi promessi, was changed for the sake of euphony shortly before its final commitment to printing.

In the early 19th century, there was still controversy as to what form the standard literary language of Italy should take. Manzoni was firmly in favour of the dialect of Florence and

Scientific Reports is run by a team of experienced editors who are experts in their fields. From our Editorial Board Members and Senior Editorial Board to our in-house Editors, we work togetherResearch integrity issue to ensure that your research is expertly handled and that we consider it to be technically sound, scientifically valid, and ultimately suitable for publication.

Interview with Rafal Marszalek, Chief Editor of Scientific Reports








 

In-house Editors

Chief Editor: Rafal Marszalek, PhD; Springer Nature, UK

Rafal's background is analytical and biological chemistry. He did his PhD and postdoctoral research in single-cell proteomics at Imperial College London, UK. He was an editor at Genome Biology before joining Scientific Reports in August

ORCID

Deputy Editor: Elizabeth Mann, PhD; Springer Nature, UK

Elizabeth has a background in pharmacology and completed her PhD in neuropharmacology at King's College London, UK. She joined Scientific Reports in January

ORCID

Deputy Editor: Sweta Naik, PhD; Springer Nature, India

Sweta has a background in Nanochemistry and completed her PhD in Chemistry from Virginia Commonwealth University, USA. Her interests lie in nanoparticle design and applications. Sweta joined Scientific Reports editorial team in and is based in the Pune office.

ORCID 

Deputy Editor: Eve Rooks, PhD; Springer Nature, UK

Eve joined Scientific Reports in , after working as an editor on the Royal Society of Chemistry’s materials chemistry and engineering portfolio for 3 years. Prior to this she completed a PhD in Earth Sciences at the University of Cambridge, UK in igneous petrology and mantle geochemistry. Her interests lie in materials for energy applications and deep earth geochemistry.

ORCID

Deputy Editor: Akila Sridhar, PhD; Springer Nature, UK

Akila joined Scientific Reports in September after working for four years with BMC Series Journals as a Senior Edito

Subpage navigation:

Lucian

Lucian&#;was&#;a Lycan who appears in Underworld, Underworld: Evolution, and Underworld: Rise of the Lycans. He was an antagonist in Underworld and the main protagonist of Underworld: Rise of the Lycans.

He was the progenitor of the lycans and the leader of the lycan resistance since the times of Viktor's enslavement. Lucian was also the lover of the VampireSonja and was largely a catalyst of the events of all Underworld films.

Underworld: Rise of the Lycans[]

Prior to Lucian's birth, no Lycans existed. Instead, a feral group of Werewolves, descended from William Corvinus, were used as slaves to the aristocratic Vampires with inconsistent success. In the early 13th century, an enslaved Werewolf gives birth to a seemingly human child, Lucian. The Vampire ElderViktor initially chooses to kill the child, but then changes his mind, curious as to what it would become. It soon becomes clear that Lucian has the ability to shift between human and Werewolf form, making him the first Lycan. Viktor uses Lucian to infect humans slaves brought to the castle for almost years, so that he can use them as his own immortal superhuman slaves. This new species is much favored compared to their predecessors, the Werewolves, since the Lycans are more docile and thus capable of comprehending orders issued by their Vampire masters, thereby replacing the Werewolves as slaves. And because Lucian is the first of his kind, Viktor prizes him above all others. Lucian himself feels no ill will towards the Vampires, rather, he rebels against his feral nature and seeks to be more sophisticated than others of his kind.

At some point during Viktor's reign, Lucian me