Complex trait of acute pancreatitis : Studies of candidate genes and adipokines

Acute pancreatitis (AP) is a common disease. Mild disease resolves spontaneously in a few days. Severe forms of the disease can lead to local complications, necrosis, and abscesses in and around the pancreas. Systemic inflammation in severe AP is associated with distant organ failures. The aim of this study is to identify genetically determined prognostic factors involved in the clinical features of AP. The study employs a candidate-gene approach, and the genes are involved in trysinogen activation in the initiation phase of the disease, as well as in the systemic inflammation as the disease proceeds. The last study examines adipokines, fat-derived hormones characterized with the capacity to modify inflammation. SPINK 1 is a gene coding trypsin activation inhibitor. Mutations N34S and P55N were determined by minisequencing methods in 371 AP patients and in 459 controls. The mutation N34S was more common in AP patients (7.8%) than in controls (2.6%). This suggests that SPINK 1 gene mutation N34S is a risk factor for AP. In the fourth study, in 12 matched pairs of patients with severe and mild AP, levels of adipokines, adiponectin, and leptin were evaluated. Plasma adipokine levels did not differ between patients with mild and severe AP. The results suggest that in AP, adipokine plasma levels are not factors predisposing to organ failures. This study identified the SPINK 1 mutation N34S to be a risk factor for AP in the general population. As AP is a multifactorial disease, and extensive genetic heterogeneity is likely, further identification of genetic factors in the disease requires larger future studies with more advanced genetic study models. Further identification of the patient characteristics associated with organ failures offers another direction of the study to achieve more detailed understanding of the severe form of AP.

Joint decoding of multiple speech patterns for robust speech recognition

We are addressing a new problem of improving automatic speech recognition performance, given multiple utterances of patterns from the same class. We have formulated the problem of jointly decoding K multiple patterns given a single Hidden Markov Model. It is shown that such a solution is possible by aligning the K patterns using the proposed Multi Pattern Dynamic Time Warping algorithm followed by the Constrained Multi Pattern Viterbi Algorithm The new formulation is tested in the context of speaker independent isolated word recognition for both clean and noisy patterns. When 10 percent of speech is affected by a burst noise at -5 dB Signal to Noise Ratio (local), it is shown that joint decoding using only two noisy patterns reduces the noisy speech recognition error rate to about 51 percent, when compared to the single pattern decoding using the Viterbi Algorithm. In contrast a simple maximization of individual pattern likelihoods, provides only about 7 percent reduction in error rate.

Multiple excitation nano-spot generation and confocal detection for far-field microscopy

An imaging technique is developed for the controlled generation of multiple excitation nano-spots for far-field microscopy. The system point spread function (PSF) is obtained by interfering two counter-propagating extended depth-of-focus PSF (DoF-PSF), resulting in highly localized multiple excitation spots along the optical axis. The technique permits (1) simultaneous excitation of multiple planes in the specimen; (2) control of the number of spots by confocal detection; and (3) overcoming the point-by-point based excitation. Fluorescence detection from the excitation spots can be efficiently achieved by Z-scanning the detector/pinhole assembly. The technique complements most of the bioimaging techniques and may find potential application in high resolution fluorescence microscopy and nanoscale imaging.

Forecasting day-ahead electricity load using a multiple equation time series approach

The quality of short-term electricity load forecasting is crucial to the operation and trading activities of market participants in an electricity market. In this paper, it is shown that a multiple equation time-series model, which is estimated by repeated application of ordinary least squares, has the potential to match or even outperform more complex nonlinear and nonparametric forecasting models. The key ingredient of the success of this simple model is the effective use of lagged information by allowing for interaction between seasonal patterns and intra-day dependencies. Although the model is built using data for the Queensland region of Australia, the method is completely generic and applicable to any load forecasting problem. The model’s forecasting ability is assessed by means of the mean absolute percentage error (MAPE). For day-ahead forecast, the MAPE returned by the model over a period of 11 years is an impressive 1.36%. The forecast accuracy of the model is compared with a number of benchmarks including three popular alternatives and one industrial standard reported by the Australia Energy Market Operator (AEMO). The performance of the model developed in this paper is superior to all benchmarks and outperforms the AEMO forecasts by about a third in terms of the MAPE criterion.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

Existence of multiple positive solutions for N-laplacian in a bounded domain in R-N

Let Ohm be a bounded domain in IRN, N greater than or equal to 2, lambda > 0, q is an element of (0, N - 1) and alpha is an element of (1, N/N-1 In this article we show the existence of at least two positive solutions for the following quasilinear elliptic problem with an exponential type nonlinearity:

Simulation of wavelength/time multiple-pulses-per-row fiber-optic CDMA network

Passive wavelength/time fiber-optic code division multiple access (WIT FO-CDMA) network is a viable option for highspeed access networks. Constructions of 2-D codes, suitable for incoherent WIT FO-CDMA, have been proposed to reduce the time spread of the 1-D sequences. The 2-D constructions can be broadly classified as 1) hybrid codes and 2) matrix codes. In our earlier work [141, we had proposed a new family of wavelength/time multiple-pulses-per-row (W/T MPR) matrix codes which have good cardinality, spectral efficiency and at the same time have the lowest off-peak autocorrelation and cross-correlation values equal to unity. In this paper we propose an architecture for a WIT MPR FO-CDAM network designed using the presently available devices and technology. A complete FO-CDMA network of ten users is simulated, for various number of simultaneous users and shown that 0 --> 1 errors can occur only when the number of interfering users is at least equal to the threshold value.

Stereochemical Analysis of Higher α,α-Dialkylglycine Containing Peptides. Characterization of Local Helical Conformations at Dipropylglycine Residues and Observation of a Novel Hydrated Multiple β-Turn Structure in Crystals of a Glycine Rich Peptide

The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the context of a poor helix promoting sequence. Single crystals of 1 were obtained in the space group P21/c with a = 13.716(2) Å, b = 12.960(2) Å, c = 22.266(4) Å, and β = 98.05(1)°; R = 6.3% for 3660 data with |Fo| > 4σ. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts φ, ψ values distorted from those expected for an ideal type II‘ β-turn (φGly(1) = +72.0°, ψGly(1) = −166.0°; φDpg(2) = −54.0°, ψDpg(2) = −46.0°) with an inserted water molecule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts φ, ψ values which lie broadly in the right handed helical region (φGly(3) = −78.0°, ψGly(3) = −9.0°; φGly(4) = −80.0°, ψGly(4) = −18.0°). There is a chiral reversal at Dpg(5) which takes up φ, ψ values in the left handed helical region. The Dpg(5)-Gly(6) segment closely resembles an ideal type I‘ β-turn (φDpg(5) = +56.0°, ψDpg(5) = +32.0°; φGly(6) = +85.0°, ψGly(6) = −3.0°). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminus forms a hydrated Schellman motif, with water insertion into the potential 6 → 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformation observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.

Multiple conformational states in crystals and in solution in alpha gamma hybrid peptides. Fragility of the C-12 helix in short sequences

The conformational properties of foldamers generated from alpha gamma hybrid peptide sequences have been probed in the model sequence Boc-Aib-Gpn-Aib-Gpn-NHMe. The choice of alpha-aminoisobutyryl (Aib) and gabapentin (Gpn) residues greatly restricts sterically accessible coil formational space. This model sequence was anticipated to be a short segment of the alpha gamma C-12 helix, stabilized by three successive 4 -> 1 hydrogen bonds, corresponding to a backbone-expanded analogue of the alpha polypeptide 3(10)-helix. Unexpectedly, three distinct crystalline polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C-12 hydrogen bonds were obtained at the N-terminus, while a novel C-17 hydrogen-bonded gamma alpha gamma turn was observed at the C-terminus. In the other two polymorphs, isolated C-9 and C-7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C-12 and C-9 turns were also crystallographically established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, respectively. Selective line broadening of NH resonances and the observation of medium range NH(i)<-> NH(i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl3 solution. The NMR results are consistent with the limited population of the continuous C-12 helix conformation. Lengthening of the (alpha gamma)(n) sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an alpha gamma C-12 helix. These results establish that conformational fragility is manifested in short hybrid alpha gamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension.

Detection of multiple source locations using a glowworm metaphor with applications to collective robotics

This paper presents a glowworm swarm based algorithm that finds solutions to optimization of multiple optima continuous functions. The algorithm is a variant of a well known ant-colony optimization (ACO) technique, but with several significant modifications. Similar to how each moving region in the ACO technique is associated with a pheromone value, the agents in our algorithm carry a luminescence quantity along with them. Agents are thought of as glowworms that emit a light whose intensity is proportional to the associated luminescence and have a circular sensor range. The glowworms depend on a local-decision domain to compute their movements. Simulations demonstrate the efficacy of the proposed glowworm based algorithm in capturing multiple optima of a multimodal function. The above optimization scenario solves problems where a collection of autonomous robots is used to form a mobile sensor network. In particular, we address the problem of detecting multiple sources of a general nutrient profile that is distributed spatially on a two dimensional workspace using multiple robots.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

Analysis of multiple crystal forms of Bacillus subtilis BacB suggests a role for a metal ion as a nucleant for crystallization

Bacillus subtilis BacB is an oxidase that is involved in the production of the antibiotic bacilysin. This protein contains two double-stranded beta-helix (cupin) domains fused in a compact arrangement. BacB crystallizes in three crystal forms under similar crystallization conditions. An interesting observation was that a slight perturbation of the crystallization droplet resulted in the nucleation of a different crystal form. An X-ray absorption scan of BacB suggested the presence of cobalt and iron in the crystal. Here, a comparative analysis of the different crystal forms of BacB is presented in an effort to identify the basis for the different lattices. It is noted that metal ions mediating interactions across the asymmetric unit dominate the different packing arrangements. Furthermore, a normalized B-factor analysis of all the crystal structures suggests that the solvent-exposed metal ions decrease the flexibility of a loop segment, perhaps influencing the choice of crystal form. The residues coordinating the surface metal ion are similar in the triclinic and monoclinic crystal forms. The coordinating ligands for the corresponding metal ion in the tetragonal crystal form are different, leading to a tighter packing arrangement. Although BacB is a monomer in solution, a dimer of BacB serves as a template on which higher order symmetrical arrangements are formed. The different crystal forms of BacB thus provide experimental evidence for metal-ion-mediated lattice formation and crystal packing.