Structure alignment based on coding of local geometric measures

BACKGROUND: A structure alignment method based on a local geometric property is presented and its performance is tested in pairwise and multiple structure alignments. In this approach, the writhing number, a quantity originating from integral formulas of Vassiliev knot invariants, is used as a local geometric measure. This measure is used in a sliding window to calculate the local writhe down the length of the protein chain. By encoding the distribution of writhing numbers across all the structures in the protein databank (PDB), protein geometries are represented in a 20-letter alphabet. This encoding transforms the structure alignment problem into a sequence alignment problem and allows the well-established algorithms of sequence alignment to be employed. Such geometric alignments offer distinct advantages over structural alignments in Cartesian coordinates as it better handles structural subtleties associated with slight twists and bends that distort one structure relative to another. RESULTS: The performance of programs for pairwise local alignment (TLOCAL) and multiple alignment (TCLUSTALW) are readily adapted from existing code for Smith-Waterman pairwise alignment and for multiple sequence alignment using CLUSTALW. The alignment algorithms employed a blocked scoring matrix (TBLOSUM) generated using the frequency of changes in the geometric alphabet of a block of protein structures. TLOCAL was tested on a set of 10 difficult proteins and found to give high quality alignments that compare favorably to those generated by existing pairwise alignment programs. A set of protein comparison involving hinged structures was also analyzed and TLOCAL was seen to compare favorably to other alignment methods. TCLUSTALW was tested on a family of protein kinases and reveal conserved regions similar to those previously identified by a hand alignment. CONCLUSION: These results show that the encoding of the writhing number as a geometric measure allow high quality structure alignments to be generated using standard algorithms of sequence alignment. This approach provides computationally efficient algorithms that allow fast database searching and multiple structure alignment. Because the geometric measure can employ different window sizes, the method allows the exploration of alignments on different, well-defined length scales

Defining the Entropy of Hierarchical Organizations

A measure of the order within a hierarchical organizational structure is proposed based on an analogy with the thermodynamic entropy of physical sciences. Organizational entropy is defined in a manner that readily allows for practical calculations. This calculation could be used to relate the order or entropy of an organization to its functional role. Additionally, it could be used to monitor the change in entropy over time and provide an impetus for periodic restructuring. This theory gives two general contributions to the entropy of an organizational structure: horizontal entropy due to changes within a level of the hierarchy and vertical entropy due to changes between levels along reporting lines within the organization. In addition to employing the thermodynamic entropy analog, identical theoretical results are obtained when calculating the Kolmogorov entropy or algorithmic complexity of an organizational hierarchy and establishes the generality of the approach. Computer simulations on model hierarchical structures show the boundaries of the vertical and horizontal contribution to entropy. It is postulated that each organization will have a specific entropy that optimizes organizational functions

Duplication Models for Biological Networks

Are biological networks different from other large complex networks? Both large biological and non-biological networks exhibit power-law graphs (number of nodes with degree k, N(k) ~ k-b) yet the exponents, b, fall into different ranges. This may be because duplication of the information in the genome is a dominant evolutionary force in shaping biological networks (like gene regulatory networks and protein-protein interaction networks), and is fundamentally different from the mechanisms thought to dominate the growth of most non-biological networks (such as the internet [1-4]). The preferential choice models non-biological networks like web graphs can only produce power-law graphs with exponents greater than 2 [1-4,8]. We use combinatorial probabilistic methods to examine the evolution of graphs by duplication processes and derive exact analytical relationships between the exponent of the power law and the parameters of the model. Both full duplication of nodes (with all their connections) as well as partial duplication (with only some connections) are analyzed. We demonstrate that partial duplication can produce power-law graphs with exponents less than 2, consistent with current data on biological networks. The power-law exponent for large graphs depends only on the growth process, not on the starting graph

Methods, Systems and Apparatuses for Radio Frequency Identification

A system for radio frequency identification (RFID) includes an enclosure defining an interior region interior to the enclosure, and a feed for generating an electromagnetic field in the interior region in response to a signal received from an RFID reader via a radio frequency (RF) transmission line and, in response to the electromagnetic field, receiving a signal from an RFID sensor attached to an item in the interior region. The structure of the enclosure may be conductive and may include a metamaterial portion, an electromagnetically absorbing portion, or a wall extending in the interior region. Related apparatuses and methods for performing RFID are provided

Methods, Systems and Apparatuses for Radio Frequency Identification

A system for radio frequency identification (RFID) includes an enclosure defining an interior region interior to the enclosure, and a feed for generating an electromagnetic field in the interior region in response to a signal received from an RFID reader via a radio frequency (RF) transmission line and, in response to the electromagnetic field, receiving a signal from an RFID sensor attached to an item in the interior region. The structure of the enclosure may be conductive and may include a metamaterial portion, an electromagnetically absorbing portion, or a wall extending in the interior region. Related apparatuses and methods for performing RFID are provided

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS: At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Abrupt global events in the Earth's history: a physics perspective

The timeline of the Earth's history reveals quasi-periodicity of the geological record over the last 542 Myr, on timescales close, in the order of magnitude, to 1 Myr. What is the origin of this quasi-periodicity? What is the nature of the global events that define the boundaries of the geological time scale? I propose that a single mechanism is responsible for all three types of such events: mass extinctions, geomagnetic polarity reversals, and sea-level fluctuations. The mechanism is fast, and involves a significant energy release. The mechanism is unlikely to have astronomical causes, both because of the energies involved, and because it acts quasi-periodically. It must then be sought within the Earth itself. And it must be capable of reversing the Earth's magnetic field. The last requirement makes it incompatible with the consensus model of the origin of the geomagnetic field - the hydromagnetic dynamo operating in the Earth's fluid core. In the second part of the paper, I show that a vast amount of seemingly unconnected geophysical and geological data can be understood in a unified way if the source of the Earth's main magnetic field is a ~200-km-thick lithosphere, repeatedly magnetized as a result of methane-driven oceanic eruptions, which produce ocean flow capable of dynamo action. The eruptions are driven by the interplay of buoyancy forces and exsolution of dissolved gas, which accumulates in the oceanic water masses prone to stagnation and anoxia. Polarity reversals, mass extinctions, and sequence boundaries are consequences of these eruptions. Unlike the consensus model of geomagnetism, this scenario is consistent with the paleomagnetic data showing that "directional changes during a [geomagnetic polarity] reversal can be astonishingly fast, possibly occurring as a nearly instantaneous jump from one inclined dipolar state to another in the opposite hemisphere".Comment: Final journal version. New title, significant changes. Supersedes v.

Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species

Genome-wide comparison of transcription factor binding between related Drosophila species highlights how sequence changes affect the biochemical events that underlie animal development