Large-scale compression of genomic sequence databases with the Burrows-Wheeler transform

Motivation The Burrows-Wheeler transform (BWT) is the foundation of many algorithms for compression and indexing of text data, but the cost of computing the BWT of very large string collections has prevented these techniques from being widely applied to the large sets of sequences often encountered as the outcome of DNA sequencing experiments. In previous work, we presented a novel algorithm that allows the BWT of human genome scale data to be computed on very moderate hardware, thus enabling us to investigate the BWT as a tool for the compression of such datasets. Results We first used simulated reads to explore the relationship between the level of compression and the error rate, the length of the reads and the level of sampling of the underlying genome and compare choices of second-stage compression algorithm. We demonstrate that compression may be greatly improved by a particular reordering of the sequences in the collection and give a novel `implicit sorting' strategy that enables these benefits to be realised without the overhead of sorting the reads. With these techniques, a 45x coverage of real human genome sequence data compresses losslessly to under 0.5 bits per base, allowing the 135.3Gbp of sequence to fit into only 8.2Gbytes of space (trimming a small proportion of low-quality bases from the reads improves the compression still further). This is more than 4 times smaller than the size achieved by a standard BWT-based compressor (bzip2) on the untrimmed reads, but an important further advantage of our approach is that it facilitates the building of compressed full text indexes such as the FM-index on large-scale DNA sequence collections.Comment: Version here is as submitted to Bioinformatics and is same as the previously archived version. This submission registers the fact that the advanced access version is now available at http://bioinformatics.oxfordjournals.org/content/early/2012/05/02/bioinformatics.bts173.abstract . Bioinformatics should be considered as the original place of publication of this article, please cite accordingl

Weak and strong electronic correlations in Fe superconductors

In this chapter the strength of electronic correlations in the normal phase of Fe-superconductors is discussed. It will be shown that the agreement between a wealth of experiments and DFT+DMFT or similar approaches supports a scenario in which strongly-correlated and weakly-correlated electrons coexist in the conduction bands of these materials. I will then reverse-engineer the realistic calculations and justify this scenario in terms of simpler behaviors easily interpreted through model results. All pieces come together to show that Hund's coupling, besides being responsible for the electronic correlations even in absence of a strong Coulomb repulsion is also the origin of a subtle emergent behavior: orbital decoupling. Indeed Hund's exchange decouples the charge excitations in the different Iron orbitals involved in the conduction bands thus causing an independent tuning of the degree of electronic correlation in each one of them. The latter becomes sensitive almost only to the offset of the orbital population from half-filling, where a Mott insulating state is invariably realized at these interaction strengths. Depending on the difference in orbital population a different 'Mottness' affects each orbital, and thus reflects in the conduction bands and in the Fermi surfaces depending on the orbital content.Comment: Book Chapte

Cyclooxygenase 2 promotes cell survival by stimulation of dynein light chain expression and inhibition of neuronal nitric oxide synthase activity

Cyclooxygenase 2 (COX-2) inhibits nerve growth factor (NGF) withdrawal apoptosis in differentiated PC12 cells. The inhibition of apoptosis by COX-2 was concomitant with prevention of caspase 3 activation. To understand how COX-2 prevents apoptosis, we used cDNA expression arrays to determine whether COX-2 regulates differential expression of apoptosis-related genes. The expression of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase [PIN]) was significantly stimulated in PC12 cells overexpressing COX-2. The COX-2-dependent stimulation of DLC expression was, at least in part, mediated by prostaglandin E(2). Overexpression of DLC also inhibited NGF withdrawal apoptosis in differentiated PC12 cells. Stimulation of DLC expression resulted in an increased association of DLC/PIN with neuronal nitric oxide synthase (nNOS), thereby reducing nNOS activity. Furthermore, nNOS expression and activity were significantly increased in differentiated PC12 cells after NGF withdrawal. This increased nNOS activity as well as increased nNOS dimer after NGF withdrawal were inhibited by COX-2 or DLC/PIN overexpression. An nNOS inhibitor or a membrane-permeable superoxide dismutase (SOD) mimetic protected differentiated PC12 cells from NGF withdrawal apoptosis. In contrast, NO donors induced apoptosis in differentiated PC12 cells and potentiated apoptosis induced by NGF withdrawal. The protective effects of COX-2 on apoptosis induced by NGF withdrawal were also overcome by NO donors. These findings suggest that COX-2 promotes cell survival by a mechanism linking increased expression of prosurvival genes coupled to inhibition of NO- and superoxide-mediated apoptosis

Competition of crystal field splitting and Hund's rule coupling in two-orbital magnetic metal-insulator transitions

Competition of crystal field splitting and Hund's rule coupling in magnetic metal-insulator transitions of half-filled two-orbital Hubbard model is investigated by multi-orbital slave-boson mean field theory. We show that with the increase of Coulomb correlation, the system firstly transits from a paramagnetic (PM) metal to a {\it N\'{e}el} antiferromagnetic (AFM) Mott insulator, or a nonmagnetic orbital insulator, depending on the competition of crystal field splitting and the Hund's rule coupling. The different AFM Mott insulator, PM metal and orbital insulating phase are none, partially and fully orbital polarized, respectively. For a small $J_{H}$ and a finite crystal field, the orbital insulator is robust. Although the system is nonmagnetic, the phase boundary of the orbital insulator transition obviously shifts to the small $U$ regime after the magnetic correlations is taken into account. These results demonstrate that large crystal field splitting favors the formation of the orbital insulating phase, while large Hund's rule coupling tends to destroy it, driving the low-spin to high-spin transition.Comment: 4 pages, 4 figure

ScanDL: A Diffusion Model for Generating Synthetic Scanpaths on Texts

Eye movements in reading play a crucial role in psycholinguistic research studying the cognitive mechanisms underlying human language processing. More recently, the tight coupling between eye movements and cognition has also been leveraged for language-related machine learning tasks such as the interpretability, enhancement, and pre-training of language models, as well as the inference of reader- and text-specific properties. However, scarcity of eye movement data and its unavailability at application time poses a major challenge for this line of research. Initially, this problem was tackled by resorting to cognitive models for synthesizing eye movement data. However, for the sole purpose of generating human-like scanpaths, purely data-driven machine-learning-based methods have proven to be more suitable. Following recent advances in adapting diffusion processes to discrete data, we propose ScanDL, a novel discrete sequence-to-sequence diffusion model that generates synthetic scanpaths on texts. By leveraging pre-trained word representations and jointly embedding both the stimulus text and the fixation sequence, our model captures multi-modal interactions between the two inputs. We evaluate ScanDL within- and across-dataset and demonstrate that it significantly outperforms state-of-the-art scanpath generation methods. Finally, we provide an extensive psycholinguistic analysis that underlines the model's ability to exhibit human-like reading behavior. Our implementation is made available at https://github.com/DiLi-Lab/ScanDL.Comment: EMNLP 202

Practical private database queries based on a quantum key distribution protocol

Private queries allow a user Alice to learn an element of a database held by a provider Bob without revealing which element she was interested in, while limiting her information about the other elements. We propose to implement private queries based on a quantum key distribution protocol, with changes only in the classical post-processing of the key. This approach makes our scheme both easy to implement and loss-tolerant. While unconditionally secure private queries are known to be impossible, we argue that an interesting degree of security can be achieved, relying on fundamental physical principles instead of unverifiable security assumptions in order to protect both user and database. We think that there is scope for such practical private queries to become another remarkable application of quantum information in the footsteps of quantum key distribution.Comment: 7 pages, 2 figures, new and improved version, clarified claims, expanded security discussio

The Effectiveness of Exercise Interventions for the Management of Frailty: A Systematic Review

This systematic review examines the effectiveness of current exercise interventions for the management of frailty. Eight electronic databases were searched for randomized controlled trials that identified their participants as “frail” either in the title, abstract, and/or text and included exercise as an independent component of the intervention. Three of the 47 included studies utilized a validated definition of frailty to categorize participants. Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review. Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults. There was a paucity of evidence to characterize the most beneficial exercise program for this population. However, multicomponent training interventions, of long duration (≥5 months), performed three times per week, for 30–45 minutes per session, generally had superior outcomes than other exercise programs. In conclusion, structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty

Efficient creation of dipolar coupled nitrogen-vacancy spin qubits in diamond

Coherently coupled pairs or multimers of nitrogen-vacancy defect electron spins in diamond have many promising applications especially in quantum information processing (QIP) but also in nanoscale sensing applications. Scalable registers of spin qubits are essential to the progress of QIP. Ion implantation is the only known technique able to produce defect pairs close enough to allow spin coupling via dipolar interaction. Although several competing methods have been proposed to increase the resulting resolution of ion implantation, the reliable creation of working registers is still to be demonstrated. The current limitation are residual radiation-induced defects, resulting in degraded qubit performance as trade-off for positioning accuracy. Here we present an optimized estimation of nanomask implantation parameters that are most likely to produce interacting qubits under standard conditions. We apply our findings to a well-established technique, namely masks written in electron-beam lithography, to create coupled defect pairs with a reasonable probability. Furthermore, we investigate the scaling behavior and necessary improvements to efficiently engineer interacting spin architectures

The Magic Number Problem for Subregular Language Families

We investigate the magic number problem, that is, the question whether there exists a minimal n-state nondeterministic finite automaton (NFA) whose equivalent minimal deterministic finite automaton (DFA) has alpha states, for all n and alpha satisfying n less or equal to alpha less or equal to exp(2,n). A number alpha not satisfying this condition is called a magic number (for n). It was shown in [11] that no magic numbers exist for general regular languages, while in [5] trivial and non-trivial magic numbers for unary regular languages were identified. We obtain similar results for automata accepting subregular languages like, for example, combinational languages, star-free, prefix-, suffix-, and infix-closed languages, and prefix-, suffix-, and infix-free languages, showing that there are only trivial magic numbers, when they exist. For finite languages we obtain some partial results showing that certain numbers are non-magic.Comment: In Proceedings DCFS 2010, arXiv:1008.127