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

Towards Communication-Efficient Quantum Oblivious Key Distribution

Oblivious Transfer, a fundamental problem in the field of secure multi-party computation is defined as follows: A database DB of N bits held by Bob is queried by a user Alice who is interested in the bit DB_b in such a way that (1) Alice learns DB_b and only DB_b and (2) Bob does not learn anything about Alice's choice b. While solutions to this problem in the classical domain rely largely on unproven computational complexity theoretic assumptions, it is also known that perfect solutions that guarantee both database and user privacy are impossible in the quantum domain. Jakobi et al. [Phys. Rev. A, 83(2), 022301, Feb 2011] proposed a protocol for Oblivious Transfer using well known QKD techniques to establish an Oblivious Key to solve this problem. Their solution provided a good degree of database and user privacy (using physical principles like impossibility of perfectly distinguishing non-orthogonal quantum states and the impossibility of superluminal communication) while being loss-resistant and implementable with commercial QKD devices (due to the use of SARG04). However, their Quantum Oblivious Key Distribution (QOKD) protocol requires a communication complexity of O(N log N). Since modern databases can be extremely large, it is important to reduce this communication as much as possible. In this paper, we first suggest a modification of their protocol wherein the number of qubits that need to be exchanged is reduced to O(N). A subsequent generalization reduces the quantum communication complexity even further in such a way that only a few hundred qubits are needed to be transferred even for very large databases.Comment: 7 page

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

A profile shape correction to reduce the vertical sensitivity of cosmic-ray neutron sensing of soil moisture

n recent years, cosmic-ray neutron sensing (CRNS) has shown a large potential among proximal sensing techniques to monitor soil moisture noninvasively, with high frequency and a large support volume (radius up to 240 m and sensing depth up to 80 cm). This signal is, however, more sensitive to closer distances and shallower depths. Inherently, CRNS-derived soil moisture is a spatially weighted value, different from an average soil moisture as retrieved by a sensor network. In this study, we systematically test a new profile shape correction on CRNS-derived soil moisture, based on additional soil moisture profile measurements and vertical unweighting, which is especially relevant during pronounced wetting or drying fronts. The analyses are conducted with data collected at four contrasting field sites, each equipped with a CRNS probe and a distributed soil moisture sensor network. After applying the profile shape correction on CRNS-derived soil moisture, it is compared with the sensor network average. Results show that the influence of the vertical sensitivity of CRNS on integral soil moisture values is successfully reduced. One to three properly located profile measurements within the CRNS support volume improve the performance. For the four investigated field sites, the RMSE decreased 11–53% when only one profile location was considered. We therefore recommend to install along with a CRNS at least one soil moisture profile in a radial distanceProfile-shape-corrected, CRNS-derived soil moisture is an unweighted integral soil moisture over the support volume, which is easier to interpret and easier to use for further applications

Orbital-selective Mott Transitions in a Doped Two-band Hubbard Model

We extend previous studies on orbital-selective Mott transitions in the paramagnetic state of the half-filled degenerate two-band Hubbard model to the general doped case, using a high-precision quantum Monte Carlo dynamical mean-field theory solver. For sufficiently strong interactions, orbital-selective Mott transitions as a function of total band filling are clearly visible in the band-specific fillings, quasiparticle weights, double occupancies, and spectra. The results are contrasted with those of single-band models for similar correlation strengths.Comment: 12 pages, 12 figure

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

In cellulo serial crystallography of alcohol oxidase crystals inside yeast cells

The possibility of using femtosecond pulses from an X-ray free-electron laser to collect diffraction data from protein crystals formed in their native cellular organelle has been explored. X-ray diffraction of submicrometre-sized alcohol oxidase crystals formed in peroxisomes within cells of genetically modified variants of the methylotrophic yeast Hansenula polymorpha is reported and characterized. The observations are supported by synchrotron radiation-based powder diffraction data and electron microscopy. Based on these findings, the concept of in cellulo serial crystallography on protein targets imported into yeast peroxisomes without the need for protein purification as a requirement for subsequent crystallization is outlined

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

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