Human pluripotent stem cells as tools for high-throughput and high-content screening in drug discovery

A significant bottleneck in drug discovery is the lack of suitable models for sensitive, reliable, and rapid assessment of lead molecules in preclinical stages of drug discovery. Human pluripotent stem cells (hPSCs) derived either from early human blastocysts (human embryonic stem cells) or by reprogramming somatic cells to a pluripotent state (human-induced pluripotent stem cells) can be propagated extensively in vitro while retaining the ability to differentiate into any specialized cell type within the body. In this review, we discuss how these unique features of hPSCs could offer a way of producing relevant in vitro models amenable to high-throughput testing for drug discovery. We summarize recent progress in inducing differentiation of hPSCs to specific cell types, and describe the ongoing efforts in applying hPSCs and their differentiated derivatives in disease modeling, drug discovery, and developmental toxicology. Moreover, we review the applications of high-content imaging assays in detecting the changes in the phenotype of hPSCs and their differentiated progeny. Finally, we highlight challenges that need to be overcome in order for the application of hPSC technology to fully benefit drug discovery

Quantum carpet interferometry for trapped atomic Bose-Einstein condensates

We propose an ``interferometric'' scheme for Bose-Einstein condensates using near-field diffraction. The scheme is based on the phenomenon of intermode traces or quantum carpets; we show how it may be used in the detection of weak forces.Comment: 4 figures. Submitted to Phys. Rev.

Identification and single-cell functional characterization of an endodermally biased pluripotent substate in human embryonic stem cells

Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state

Simple method for excitation of a Bose-Einstein condensate

An appropriate, time-dependent modification of the trapping potential may be sufficient to create effectively collective excitations in a cold atom Bose-Einstein condensate. The proposed method is complementary to earlier suggestions and should allow the creation of both dark solitons and vortices.Comment: 8 pages, 7 figures, version accepted for publication in Phys. Rev.

Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).This work was funded by the Medical Research Council (Clinical Research Training Fellowship to DP and grant G0801213 to M.K. Maini)

Leptodora kindtii survival in the laboratory

Leptodora kindtii , a pelagic predatory cladoceran, suffers high mortality on transfer to laboratory, which makes the experimental work difficult. We investigated the causes of high mortality, using four variables: water volume, animal density, light intensity, and origin of water for culturing, i.e., water from native or a non-native lake. For the experiments we used Leptodora and water from Lake Loosdrecht and Lake Maarsseveen (The Netherlands). Water was found to be the most important factor; the animals did not necessarily do better in lake water from which they were collected. Water volume and animal density were of limited importance, and light intensity did not affect survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41752/1/10452_2004_Article_DO00000328.pd

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale