1,288 research outputs found
CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq
No full textSingle-cell transcriptomics requires a method that is sensitive, accurate, and reproducible. Here, we present CEL-Seq2, a modified version of our CEL-Seq method, with threefold higher sensitivity, lower costs, and less hands-on time. We implemented CEL-Seq2 on Fluidigm’s C1 system, providing its first single-cell, on-chip barcoding method, and we detected gene expression changes accompanying the progression through the cell cycle in mouse fibroblast cells. We also compare with Smart-Seq to demonstrate CEL-Seq2’s increased sensitivity relative to other available methods. Collectively, the improvements make CEL-Seq2 uniquely suited to single-cell RNA-Seq analysis in terms of economics, resolution, and ease of use.Seventh Framework Programme (European Commission)Israel Science Foundatio
The Einstein-Podolsky-Rosen Argument and the Bell Inequalities
No full textIn 1935 Einstein, Podolsky, and Rosen (EPR) published an important paper in which they claimed that the whole formalism of quantum mechanics together with what they called ``Reality Criterion'' imply that quantum mechanics cannot be complete. That is, there must exist some elements of reality that are not described by quantum mechanics. There must be, they concluded, a more complete description of physical reality behind quantum mechanics. There must be a state, a hidden variable, characterizing the state of affairs in the world in more details than the quantum mechanical state, something that also reflects the missing elements of reality. Under some further but quite plausible assumptions, this conclusion implies that in some spin-correlation experiments the measured quantum mechanical probabilities should satisfy particular inequalities (Bell-type inequalities). The paradox consists in the fact that quantum probabilities do not satisfy these inequalities. And this paradoxical fact has been confirmed by several laboratory experiments in the last three decades. The problem is still open and hotly debated among both physicists and philosophers. It has motivated a wide range of research from the most fundamental quantum mechanical experiments through foundations of probability theory to the theory of stochastic causality as well as the metaphysics of free will
Rosen-menetelmä teatterin työvälineenä
No full textTämän opinnäytetyön tavoitteena on selvittää Rosen-menetelmää ja sen käyttömahdollisuuksia näyttämöesityksen valmistelussa ja teatterin työvälineenä. Se kuvaa, mitä Rosen-menetelmä on, mitä annettavaa sillä voi olla näyttelijäntyöhön ja roolin rakentamiseen sekä miten menetelmää voi hyödyntää teatteri-ilmaisun ohjaajan työssä soveltavan teatterin toteutuksissa.
Rosen-menetelmällä tarkoitetaan Marion Rosenin kehittämää Rosen-hoitoa ja siitä syntynyttä Rosen-liikuntaa. Suomessa Rosen-hoitoa antavat tehtävään koulutetut Rosen-terapeutit. Rosen-menetelmä kuuluu kehoterapioihin. Kun puhutaan menetelmän hyödyntämisestä teatterin työvälineenä, voidaan Rosen-menetelmää lähestyä somaattisena menetelmänä.
Somaattisia liikemenetelmiä ovat esimerkiksi hahmometodi, Autenttinen liike -työskentely, Alexander-tekniikka ja Feldenkrais-menetelmä.
Opinnäytetyötä varten on haastateltu kolmea Rosen-menetelmän tuntijaa. Yksi heistä on dramaturgi ja näytelmäkäsikirjoittaja, joka opiskelee Rosen-menetelmää. Toinen haastatelluista on Rosen-terapeutti ja harrastajateatterilainen. Kolmas heistä on Rosen-terapeutti ja
menetelmän kouluttaja. Opinnäytetyön toisena lähteenä toimii opinnäytteen tekijän omakohtaisesta Rosen-hoitoon osallistumisesta syntynyt työpäiväkirja ja sitä seurannut esityksellinen tutkielma sekä nukkenäytelmäkäsikirjoitus.
Rosen-menetelmää voidaan käyttää teatterin työvälineenä samalla tapaa kuin muita somaattisia menetelmiä. Esittävän taiteen tekijä voi menetelmän kautta lisätä omaa kehotietämystään. Rosen-liikunta tarjoaa esittävän taiteen tekijöille kehollisia harjoitteita, joita voidaan soveltaa esimerkiksi esityksen harjoitusprosessissa. Rosen-hoidon voi myös kytkeä osaksi esityksen valmistamisen prosessia. Esimerkkinä tästä opinnäytetyö esittelee näytelmäkäsikirjoitus- ja ohjausprosessin, jossa Rosen-terapeutiksi opiskeleva ohjaaja käytti menetelmää näyttelijän ja ohjaajan dialogin välineenä.
Kuten muidenkin somaattisten menetelmien, myös Rosen-menetelmän käyttö vaatii riittävän ammattitaidon menetelmän soveltamiseen. Kun terapiaa tai hoitoa sovelletaan teatterin työvälineeksi, on oltava hyvin tietoinen siitä, mitä menetelmällä tahdotaan.The aim of this thesis is to examine the Rosen Method and the method’s usability in the preparation of a stage play and as a tool in theatre making. The thesis concentrates on determining the method, in solving its viability in actor’s work and in constructing roles. The work also describes how the method can be used in Drama Instructor’s work in applied theatre productions.
The Rosen Method refers to Marion Rosen’s Rosen treatment and the Rosen bodywork which evolved from the treatment. In Finland, Rosen therapy is practised by trained Rosen therapists. The Rosen Method is a form of body therapy. When the method is used as a tool in theatre, the method can be approached as a somatic method. Somatic movement methods include for instance Gestalt Therapy, Authentic Movement Method, Alexander Technique and Feldenkreis Method.
For this thesis, three Rosen Method experts were interviewed. One is a dramaturge and a playwright, who studies the method. Another interviewee is a Rosen therapist and an active participant in amateur theatre. The third one is a Rosen therapist and instructor of the method. As a second source of the thesis the author presents both his work dairy written during his participation in Rosen treatment as well as the performance study and a script for a puppet play, which followed the treatment.
Rosen Method can be used as a tool in theatre in the same way as other somatic methods. Through the method, the performing arts maker can increase his or her own body consciousness. Rosen bodywork provides performing arts makers with bodily rehearsals, which can be applied in the process of constructing a performance. The Rosen treatment can also be linked in with the production process of the performance. As an example of this, the thesis presents a playwriting and a directing process, in which a director, who studies to become a Rosen therapist used the method as a tool for dialogue between the director and the actor.
As is the case with other somatic methods, the application of the Rosen method requires a sufficient amount of professionalism. When the therapy or treatment is applied as a tool in theatre-making, the goals of the method must be well determined
"Gross Rosen" by Mieczyslaw Moldawa, Polish language excerpt, several pages
No full textA photocopy of pages 51, 238, 250, and 278 of the book "Gross Rosen--A Concentration Camp in Silesia" by Mieczyslaw Moldawa in the original Polish language. Marian Wojciechowski is mentioned on these pages. The photocopy of the title page is inscribed and signed by the author
Penalty Formulation for Zero-One Nonlinear Programming
No full textRaghavachar, has shown the equivalence of zero-one integer programming and a concave quadratic penalty function for a sufficiently large value of the penalty. Kalantari and Rosen found a lower bound for this penalty. It was also shown that this penalty could not be reduced in specific cases. We show that the results generalize to the case where the objective function is any concave function. Equivalent penalty formulation for non-concave functions is also considered.Technical report DCS-TR-14
Abstract 3037: Dissecting treatment resistance in patients with ovarian cancer and PDX-models using single-cell RNA-sequencing
No full textAbstract
Background: Ovarian cancer (OvCa) is frequently associated with malignant effusions, which are complex ecosystems with heterogeneous populations of malignant cells and non-malignant cells. Bulk RNA-seq or whole-exome sequencing (WES) only reflect average cellular behavior and thereby mask intrinsic cell diversity with potential relevance for treatment resistance.
Approach: To overcome some of these barriers, we applied single-cell RNA-sequencing (scRNA-seq) to malignant and non-malignant cells isolated from patients with platinum treatment resistant disease. Furthermore, we used patient-derived xenograft (PDX) cohorts, in which we isolated cells for scRNA-seq from vehicle tumors (VEH), treated the other models with carboplatin, and harvested cells at the time of minimal residual disease (MRD) or disease progression (PROG).
Results: To date, we have profiled ~12000 single cells from 12 patients with treatment naïve (n=3) or platinum-resistant disease (n=9), including sequential sampling in 3 patients with resistant disease. We observed significant inter- and intra-individual transcriptional heterogeneity in malignant cells. A recurrent pattern across resistant patients was the differential expression of inflammatory pathways in a subset of cells. In a patient with three consecutive specimens, we observed increasing accumulation of cells expressing a cell state characterized by tumor necrosis factor alpha (TNF-a) signaling, Importantly, these cells were genetically identical to the entire population, supporting the hypothesis that non-encoded mechanisms conferred treatment resistance. In a BRCA-mutant patient, unbiased analysis identified a stemness program in a subpopulation of cells, which was genetically identical to other cells, indicating phenotypic conversion. To systemically interrogate mechanisms of resistance to platinum therapy, sequenced single cells isolated from PDX models at three time points (VEH, MRD and PROG). In a BRCA-WT PDX model, resistant cells isolated at MRD and PROG shared a transcriptional program that was dominated by expression of a STAT3 program. Ex vivo cultures from platinum-resistant patients were exquisitely sensitivity to JAK/STAT3-inhibitor. Live cell imaging revealed that STAT3-inhibition prevented spheroid formation, attachment and clearance through a mesothelial monolayer in vitro.
Conclusion: Our results indicate that non-encoded mechanisms play an important role in the development of treatment resistance in ovarian cancer. Our initial studies indicate an important role of inflammatory pathways in treatment resistance, in particular STAT3 signaling, which can be overcome with specific inhibitors at nanomolar concentrations. These data suggests that single-cell profiling can be performed on clinical ovarian cancer specimens and may yield novel therapeutic avenues for patients with treatment-resistant ovarian cancer.
Citation Format: Benjamin Izar, Itay Tirosh, Elizabeth Stover, Asaf Rotem, Parin Shah, Mike Cuoco, Chris Rodman, Joyce Liu, Ursula Matulonis, Orit Rozenblatt-Rosen, Levi Garraway, Aviv Regev. Dissecting treatment resistance in patients with ovarian cancer and PDX-models using single-cell RNA-sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3037. doi:10.1158/1538-7445.AM2017-3037</jats:p
Quantum information entropies for an asymmetric trigonometric Rosen–Morse potential
No full textShannon entropy for the position and momentum eigenstates
of an asymmetric trigonometric Rosen–Morse potential
for the ground and first excited states is evaluated. The
position and momentum information entropies Sx and Sp
are calculated numerically. Also, we find that S1
x is obtained
analytically and increases with the potential depth and
width. Some interesting features of the information entropy
densities ρs (x) and ρs (p) are demonstrated graphically.
The Bialynicki-Birula–Mycielski inequality is also tested and
found to hold good
The menin tumor suppressor protein is phosphorylated in response to DNA damage.
No full textMultiple endocrine neoplasia type 1 (MEN1) is a heritable cancer syndrome characterized by tumors of the pituitary, pancreas and parathyroid. Menin, the product of the MEN1 gene, is a tumor suppressor protein that functions in part through the regulation of transcription mediated by interactions with chromatin modifying enzymes.Here we show menin association with the 5' regions of DNA damage response genes increases after DNA damage and is correlated with RNA polymerase II association but not with changes in histone methylation. Furthermore, we were able to detect significant levels of menin at the 3' regions of CDKN1A and GADD45A under conditions of enhanced transcription following DNA damage. We also demonstrate that menin is specifically phosphorylated at Ser394 in response to several forms of DNA damage, Ser487 is dynamically phosphorylated and Ser543 is constitutively phosphorylated. Phosphorylation at these sites however does not influence the ability to interact with histone methyltransferase activity. In contrast, the interaction between menin and RNA polymerase II is influenced by phosphorylation, whereby a phospho-deficient mutant had a higher affinity for the elongating form of RNA polymerase compared to wild type. Additionally, a subset of MEN1-associated missense point mutants, fail to undergo DNA damage dependent phosphorylation.Together, our findings suggest that the menin tumor suppressor protein undergoes DNA damage induced phosphorylation and participates in the DNA damage transcriptional response
A Great Big Cuddle, poems for the very young, illustrated by Chris Riddell
No full textCurl up with a playful collection of poems from best-selling children’s author and poet Michael Rosen, perfect for sharing with young friends.
In this exuberant compilation, Michael Rosen invites children to joyfully celebrate sounds and the infinite possibilities of language. Nonsense verses with the feel of classic nursery rhymes tickle the ear and set feet tapping while expressive illustrations by Chris Riddell illuminate the larger-than-life characters. With subject matter that runs the gamut of a child’s emotional range from hungry and angry to wiggly and giggly, these thirty-six clever poems will delight little listeners
BBC Radio 4 - Word of Mouth, Language and Gender Identity
No full textMichael Rosen and Dr Laura Wright are joined by CN Lester, author of 'Trans Like Me: A Journey for All of Us' to talk about language and gender identity. What does it mean to be transgender and how is language being used (by and about) people who identify as transgender, non-binary or genderqueer
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