Adiabatic population transfer via multiple intermediate states

This paper discusses a generalization of stimulated Raman adiabatic passage (STIRAP) in which the single intermediate state is replaced by $N$ intermediate states. Each of these states is connected to the initial state \state{i} with a coupling proportional to the pump pulse and to the final state \state{f} with a coupling proportional to the Stokes pulse, thus forming a parallel multi-$\Lambda$ system. It is shown that the dark (trapped) state exists only when the ratio between each pump coupling and the respective Stokes coupling is the same for all intermediate states. We derive the conditions for existence of a more general adiabatic-transfer state which includes transient contributions from the intermediate states but still transfers the population from state \state{i} to state \state{f} in the adiabatic limit. We present various numerical examples for success and failure of multi-$\Lambda$ STIRAP which illustrate the analytic predictions. Our results suggest that in the general case of arbitrary couplings, it is most appropriate to tune the pump and Stokes lasers either just below or just above all intermediate states.Comment: 14 pages, two-column revtex style, 10 figure

STIRAP transport of Bose-Einstein condensate in triple-well trap

The irreversible transport of multi-component Bose-Einstein condensate (BEC) is investigated within the Stimulated Adiabatic Raman Passage (STIRAP) scheme. A general formalism for a single BEC in M-well trap is derived and analogy between multi-photon and tunneling processes is demonstrated. STIRAP transport of BEC in a cyclic triple-well trap is explored for various values of detuning and interaction between BEC atoms. It is shown that STIRAP provides a complete population transfer at zero detuning and interaction and persists at their modest values. The detuning is found not to be obligatory. The possibility of non-adiabatic transport with intuitive order of couplings is demonstrated. Evolution of the condensate phases and generation of dynamical and geometric phases are inspected. It is shown that STIRAP allows to generate the unconventional geometrical phase which is now of a keen interest in quantum computing.Comment: 9 pages, 6 figures. To be published in Laser Physics (v. 19, n.4, 2009

Momentum transfer using chirped standing wave fields: Bragg scattering

We consider momentum transfer using frequency-chirped standing wave fields. Novel atom-beam splitter and mirror schemes based on Bragg scattering are presented. It is shown that a predetermined number of photon momenta can be transferred to the atoms in a single interaction zone.Comment: 4 pages, 3 figure

Quantum computation with trapped polar molecules

We propose a novel physical realization of a quantum computer. The qubits are electric dipole moments of ultracold diatomic molecules, oriented along or against an external electric field. Individual molecules are held in a 1-D trap array, with an electric field gradient allowing spectroscopic addressing of each site. Bits are coupled via the electric dipole-dipole interaction. Using technologies similar to those already demonstrated, this design can plausibly lead to a quantum computer with $\gtrsim 10^4$ qubits, which can perform $\sim 10^5$ CNOT gates in the anticipated decoherence time of $\sim 5$ s.Comment: 4 pages, RevTeX 4, 2 figures. Edited for length and converted to RevTeX, but no substantial changes from earlier pdf versio

Feshbach-Stimulated Photoproduction of a Stable Molecular Condensate

Photoassociation and the Feshbach resonance are, in principle, feasible means for creating a molecular Bose-Einstein condensate from an already-quantum-degenerate gas of atoms; however, mean-field shifts and irreversible decay place practical constraints on the efficient delivery of stable molecules using either mechanism alone. We therefore propose Feshbach-stimulated Raman photoproduction, i.e., a combination of magnetic and optical methods, as a viable means to collectively convert degenerate atoms into a stable molecular condensate with near-unit efficiency.Comment: 5 pages, 3 figures, 1 table; v3 includes few-level diagram of scheme, and added discussion; transferred to PR

Epigenetic Silencing of Nucleolar rRNA Genes in Alzheimer's Disease

Background: Ribosomal deficits are documented in mild cognitive impairment (MCI), which often represents an early stage Alzheimer’s disease (AD), as well as in advanced AD. The nucleolar rRNA genes (rDNA), transcription of which is critical for ribosomal biogenesis, are regulated by epigenetic silencing including promoter CpG methylation. Methodology/Principal Findings: To assess whether CpG methylation of the rDNA promoter was dysregulated across the AD spectrum, we analyzed brain samples from 10 MCI-, 23 AD-, and, 24 age-matched control individuals using bisulfite mapping. The rDNA promoter became hypermethylated in cerebro-cortical samples from MCI and AD groups. In parietal cortex, the rDNA promoter was hypermethylated more in MCI than in advanced AD. The cytosine methylation of total genomic DNA was similar in AD, MCI, and control samples. Consistent with a notion that hypermethylation-mediated silencing of the nucleolar chromatin stabilizes rDNA loci, preventing their senescence-associated loss, genomic rDNA content was elevated in cerebrocortical samples from MCI and AD groups. Conclusions/Significance: In conclusion, rDNA hypermethylation could be a new epigenetic marker of AD. Moreover, silencing of nucleolar chromatin may occur during early stages of AD pathology and play a role in AD-related ribosoma

Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome

The purpose of the present study is to identify genes that contribute to cell proliferation or differentiation of breast cancers independent of signalling through the oestrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2). An oligonucleotide microarray assayed 40 tumour samples from ER(+)/HER2(−), ER(+)/HER2(+), ER(−)/HER2(+), and ER(−)/HER2(−) breast cancer tissues. Quantitative reverse transcriptase PCR detected overexpression of a cell cycle-related transcription factor, E2F-5, in ER-negative breast cancers, and fluorescence in situ hybridisation detected gene amplification of E2F-5 in 5 out of 57 (8.8%) breast cancer samples. No point mutations were found in the DNA-binding or DNA-dimerisation domain of E2F-5. Immunohistochemically, E2F-5-positive cancers correlated with a higher Ki-67 labelling index (59.5%, P=0.001) and higher histological grades (P=0.049). E2F-5-positive cancers were found more frequently in ER(−)/progesterone receptor (PgR)(−)/HER2(−) cancer samples (51.9%, P=0.0049) and in breast cancer samples exhibiting a basal phenotype (56.0%, P=0.0012). Disease-free survival in node-negative patients with E2F-5-positive cancers was shorter than for patients with E2F-5-negative cancers. In conclusion, we identify, for the first time, a population of breast cancer cells that overexpress the cell cycle-related transcription factor, E2F-5. This E2F-5-positive breast cancer subtype was associated with an ER(−)/PgR(−)/HER2(−) status, a basal phenotype, and a worse clinical outcome

Generation of Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells

Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH−/− mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH−/−-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH−/− iPS cell lines, we aggregated FAH−/−-iPS cells with tetraploid embryos and obtained entirely FAH−/−-iPS cell–derived mice that were viable and exhibited the phenotype of the founding FAH−/− mice. Then, we transduced FAH cDNA into the FAH−/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell–derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models

Location patterns of urban industry in Shanghai and implications for sustainability

China’s economy has undergone rapid transition and industrial restructuring. The term “urban industry” describes a particular type of industry within Chinese cities experiencing restructuring. Given the high percentage of industrial firms that have either closed or relocated from city centres to the urban fringe and beyond, emergent global cities such as Shanghai, are implementing strategies for local economic and urban development, which involve urban industrial upgrading numerous firms in the city centre and urban fringe. This study aims to analyze the location patterns of seven urban industrial sectors within the Shanghai urban region using 2008 micro-geography data. To avoid Modifiable Areal Unit Problem (MAUP) issue, four distance-based measures including nearest neighbourhood analysis, Kernel density estimation, K-function and co-location quotient have been extensively applied to analyze and compare the concentration and co-location between the seven sectors. The results reveal disparate patterns varying with distance and interesting co-location as well. The results are as follows: the city centre and the urban fringe have the highest intensity of urban industrial firms, but the zones with 20–30 km from the city centre is a watershed for most categories; the degree of concentration varies with distance, weaker at shorter distance, increasing up to the maximum distance of 30 km and then decreasing until 50 km; for all urban industries, there are three types of patterns, mixture of clustered, random and dispersed distribution at a varied range of distances. Consequently, this paper argues that the location pattern of urban industry reflects the stage-specific industrial restructuring and spatial transformation, conditioned by sustainability objectives

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/