Accurate estimation of isoelectric point of protein and peptide based on amino acid sequences

Motivation: In any macromolecular polyprotic system - for example protein, DNA or RNA - the isoelectric point - commonly referred to as the pI - can be defined as the point of singularity in a titration curve, corresponding to the solution pH value at which the net overall surface charge - and thus the electrophoretic mobility - of the ampholyte sums to zero. Different modern analytical biochemistry and proteomics methods depend on the isoelectric point as a principal feature for protein and peptide characterization. Protein separation by isoelectric point is a critical part of 2-D gel electrophoresis, a key precursor of proteomics, where discrete spots can be digested in-gel, and proteins subsequently identified by analytical mass spectrometry. Peptide fractionation according to their pI is also widely used in current proteomics sample preparation procedures previous to the LC-MS/MS analysis. Therefore accurate theoretical prediction of pI would expedite such analysis. While such pI calculation is widely used, it remains largely untested, motivating our efforts to benchmark pI prediction methods. Results: Using data from the database PIP-DB and one publically available dataset as our reference gold standard, we have undertaken the benchmarking of pI calculation methods. We find that methods vary in their accuracy and are highly sensitive to the choice of basis set. The machine-learning algorithms, especially the SVM-based algorithm, showed a superior performance when studying peptide mixtures. In general, learning-based pI prediction methods (such as Cofactor, SVM and Branca) require a large training dataset and their resulting performance will strongly depend of the quality of that data. In contrast with Iterative methods, machine-learning algorithms have the advantage of being able to add new features to improve the accuracy of prediction. Contact: yperez@ebi.ac.uk Availability and Implementation: The software and data are freely available at https://github.com/ypriverol/pIR. Supplementary information: Supplementary data are available at Bioinformatics online.

Osmotic flow in porous membranes:effects of electric charge

The electrostatic model for osmotic flow across a porous membrane in our previous study (Akinaga et al. 2008)" was extended to include the streaming potential, for solutes and pores of like charge and fixed surface charge densities. The magnitude of the streaming potential was determined to satisfy zero current condition along the pore axis. It was found that the streaming potential affects the velocity profiles of the pressure driven flow as well as the osmotic flow through the pore, and decreases their flow rates, particularly in the case of large Debye length relative to the pore radius, whereas it has little effect on the reflection coefficients of spherical solutes through cylindrical pores.

Effects of electric charge on osmotic flow across periodically arranged circular cylinders

An electrostatic model is developed for osmotic flow across a layer consisting of identical circular cylinders with a fixed surface charge, aligned parallel to each other so as to form an ordered hexagonal arrangement. The expression of the osmotic reflection coefficient is derived for spherical solutes with a fixed surface charge suspended in an electrolyte, based on low-Reynolds-number hydrodynamics and a continuum, point-charge description of the electric double layers. The repulsive electrostatic interaction between the surface charges with the same sign on the solute and the cylinders is shown to increase the exclusion region of solute from the cylinder surface, which enhances the osmotic flow. Applying the present model to the study of osmotic flow across the endothelial surface glycocalyx of capillary walls has revealed that this electrostatic model could account well for the reflection coefficients measured for charged macromolecules, such as albumin, in the physiological range of charge density and ion concentration.

Refractive index sensitivity characteristics near the dispersion turning point of the multimode microfiber-based Mach–Zehnder interferometer

The turning point of the refractive index (RI) sensitivity based on the multimode microfiber (MMMF) in-line Mach–Zehnder interferometer (MZI) is observed. By tracking the resonant wavelength shift of the MZI generated between the HE11 and HE12 modes in the MMMF, the surrounding RI (SRI) could be detected. Theoretical analysis demonstrates that the RI sensitivity will reach ±∞ on either side of the turning point due to the group effective RI difference (퐺) approaching zero. Significantly, the positive sensitivity exists in a very wide fiber diameter range, while the negative sensitivity can be achieved in a narrow diameter range of only 0.3 μm. Meanwhile, the experimental sensitivities and variation trend at different diameters exhibit high consistency with the theoretical results. High RI sensitivity of 10777.8 nm/RIU (RI unit) at the fiber diameter of 4.6 μm and the RI around 1.3334 is realized. The discovery of the sensitivity turning points has great significance on trace detection due to the possibility of ultrahigh RI sensitivity.

Political discourse analysis from the point of view of translation studies

Political discourse very often relies on translation. Political Discourse Analysis (PDA), however, has not yet taken full account of the phenomenon of translation. This paper argues that the disciplines of Translation Studies (TS) and PDA can benefit from closer cooperation. It starts by presenting examples of authentic translations of political texts, commenting on them from the point of view of TS. These examples concern political effects caused by specific translation solutions; the processes by which information is transferred via translation to another culture; and the structure and function of equally valid texts in their respective cultures. After a brief survey of the discipline of Translation Studies, the paper concludes with outlining scope for interdisciplinary cooperation between PDA and TS. This is illustrated with reference to an awareness of product features, multilingual texts, process analysis, and the politics of translation.

A concept-based framework for retrieving evidence to support emergency physician decision making at the point of care

The goal of evidence-based medicine is to uniformly apply evidence gained from scientific research to aspects of clinical practice. In order to achieve this goal, new applications that integrate increasingly disparate health care information resources are required. Access to and provision of evidence must be seamlessly integrated with existing clinical workflow and evidence should be made available where it is most often required - at the point of care. In this paper we address these requirements and outline a concept-based framework that captures the context of a current patient-physician encounter by combining disease and patient-specific information into a logical query mechanism for retrieving relevant evidence from the Cochrane Library. Returned documents are organized by automatically extracting concepts from the evidence-based query to create meaningful clusters of documents which are presented in a manner appropriate for point of care support. The framework is currently being implemented as a prototype software agent that operates within the larger context of a multi-agent application for supporting workflow management of emergency pediatric asthma exacerbations. © 2008 Springer-Verlag Berlin Heidelberg.

Stopping the clock on proteomic degradation by heat treatment at the point of tissue excision

The effectiveness of rapid and controlled heating of intact tissue to inactivate native enzymatic activity and prevent proteome degradation has been evaluated. Mouse brains were bisected immediately following excision, with one hemisphere being heat treated followed by snap freezing in liquid nitrogen while the other hemisphere was snap frozen immediately. Sections were cut by cryostatic microtome and analyzed by MALDI-MS imaging and minimal label 2-D DIGE, to monitor time-dependent relative changes in intensities of protein and peptide signals. Analysis by MALDI-MS imaging demonstrated that the relative intensities of markers varied across a time course (0-5 min) when the tissues were not stabilized by heat treatment. However, the same markers were seen to be stabilized when the tissues were heat treated before snap freezing. Intensity profiles for proteins indicative of both degradation and stabilization were generated when samples of treated and nontreated tissues were analyzed by 2-D DIGE, with protein extracted before and after a 10-min warming of samples. Thus, heat treatment of tissues at the time of excision is shown to prevent subsequent uncontrolled degradation of tissues at the proteomic level before any quantitative analysis, and to be compatible with downstream proteomic analysis.

Fundamental characteristics of space-charge waves in photorefractive sillenite crystals

We investigate experimentally the fundamental characteristics of space-charge waves excited in a photorefractive crystal of Bi12SiO20. Features such as their transient rise and decay as well as their steady-state frequency response are investigated. Based on this, we find the dependence of the space-charge waves' quality factor on spatial frequency and electric-field biasing. The experimental findings are compared with the linear space-charge wave theory developed previously by Sturman et al. [J. Opt. Sec. Am. B 10, 1919 (1993)].

Fundamental characteristics of space-charge waves in photorefractive sillenite crystals

We investigate experimentally the fundamental characteristics of space-charge waves excited in a photorefractive crystal of Bi12SiO20. Features such as their transient rise and decay as well as their steady-state frequency response are investigated. Based on this, we find the dependence of the space-charge waves' quality factor on spatial frequency and electric-field biasing. The experimental findings are compared with the linear space-charge wave theory developed previously by Sturman et al. [J. Opt. Sec. Am. B 10, 1919 (1993)].

The pro-reform movement led by Avenir de la Francaise:a point of leverage in the French political process?

The study examines factors influencing language planning decisions in contemporary France. It focuses upon the period 1992-1994, which witnessed the introduction of two major language policy measures, the first an amendment to the French Constitution, in 1992, proclaiming the language of the Republic as French, the second, in 1994, legislation to extend the ambit of the loi Bas-Lauriol, governing the use of the French language in France. The thesis posits a significant role for the pro-reform movement led by the French language association Avenir de la Langue Francaise (ALF) in the introduction and formulation of the policy measures concerned. The movement is depicted as continuing the traditional pattern of intellectual involvement in language planning, whilst also marking the beginning of a highly proactive, and increasingly political approach. Detailed examination of the movement's activities reveals that contextual factors and strategic strength combined to facilitate access to the levers of power, and enabled those involved to exert an impact on policy initiation, formulation, and ultimately implementation. However, ALF's decision to pursue the legislative route led to the expansion of the network of actors involved in language policymaking, and the development of counter-pressure from sectoral groups. It is suggested that this more interventionist approach destabilised the traditionally consensual language policy community, and called into question the quasi-monopoly of the intelligentsia in respect of language policymaking. It raised broader questions relating to freedom of expression and the permissible limits of language regulation in a democracy such as France. It also exposed ongoing ambiguities and inconsistencies in the interpretation of the tenets of language planning.

Clinical decision support system for point of care use: ontology driven design and software implementation

OBJECTIVES: The objective of this research was to design a clinical decision support system (CDSS) that supports heterogeneous clinical decision problems and runs on multiple computing platforms. Meeting this objective required a novel design to create an extendable and easy to maintain clinical CDSS for point of care support. The proposed solution was evaluated in a proof of concept implementation. METHODS: Based on our earlier research with the design of a mobile CDSS for emergency triage we used ontology-driven design to represent essential components of a CDSS. Models of clinical decision problems were derived from the ontology and they were processed into executable applications during runtime. This allowed scaling applications' functionality to the capabilities of computing platforms. A prototype of the system was implemented using the extended client-server architecture and Web services to distribute the functions of the system and to make it operational in limited connectivity conditions. RESULTS: The proposed design provided a common framework that facilitated development of diversified clinical applications running seamlessly on a variety of computing platforms. It was prototyped for two clinical decision problems and settings (triage of acute pain in the emergency department and postoperative management of radical prostatectomy on the hospital ward) and implemented on two computing platforms-desktop and handheld computers. CONCLUSIONS: The requirement of the CDSS heterogeneity was satisfied with ontology-driven design. Processing of application models described with the help of ontological models allowed having a complex system running on multiple computing platforms with different capabilities. Finally, separation of models and runtime components contributed to improved extensibility and maintainability of the system.

Automatic indexing and retrieval of encounter-specific evidence for point-of-care support

Evidence-based medicine relies on repositories of empirical research evidence that can be used to support clinical decision making for improved patient care. However, retrieving evidence from such repositories at local sites presents many challenges. This paper describes a methodological framework for automatically indexing and retrieving empirical research evidence in the form of the systematic reviews and associated studies from The Cochrane Library, where retrieved documents are specific to a patient-physician encounter and thus can be used to support evidence-based decision making at the point of care. Such an encounter is defined by three pertinent groups of concepts - diagnosis, treatment, and patient, and the framework relies on these three groups to steer indexing and retrieval of reviews and associated studies. An evaluation of the indexing and retrieval components of the proposed framework was performed using documents relevant for the pediatric asthma domain. Precision and recall values for automatic indexing of systematic reviews and associated studies were 0.93 and 0.87, and 0.81 and 0.56, respectively. Moreover, precision and recall for the retrieval of relevant systematic reviews and associated studies were 0.89 and 0.81, and 0.92 and 0.89, respectively. With minor modifications, the proposed methodological framework can be customized for other evidence repositories. © 2010 Elsevier Inc.

Tuning of the charge in octahedral ferric complexes based on pyridoxal-N substituted thiosemicarbazone ligands

Four novel mononuclear coordination compounds namely: [Fe(Hthpy)2](SO4)1/2·3.5H2O 1, [Fe(Hthpy)2]NO3·3H2O 2, [Fe(H2mthpy)2](CH3C6H4SO3)3·CH3CH2OH 3 and [Fe(Hethpy)(ethpy)]·8H2O 4, (H2thpy = pyridoxalthiosemicarbazone, H2mthpy = pyridoxal-4-methylthiosemicarbazone, H2ethpy = pyridoxal-4-ethylthiosemicarbazone), were synthesized in the absence or presence of organic base, Et3N and NH3. Compounds 1 and 2 are monocationic, and were prepared using the singly deprotonated form of pyridoxalthiosemicarbazone. Both compounds crystallise in the monoclinic system, C2/c and P21/c space group for 1 and 2, respectively. Complex 3 is tricationic, it is formed with neutral bis(ligand) complex and possesses an interesting 3D channel architecture, the unit cell is triclinic, P1 space group. For complex 4, the pH value plays an important role during its synthesis; 4 is neutral and crystallises with two inequivalent forms of the ligand: the singly and the doubly deprotonated chelate of H2ethpy, the unit cell is monoclinic, C2/c space group. Notably, in 1 and 4, there is an attractive infinite three dimensional hydrogen bonding network in the crystal lattice. Magnetic measurements of 1 and 4 revealed that a rather steep spin transition from the low spin to high spin Fe(III) states occurs above 300 K in the first heating step. This transition is accompanied by the elimination of solvate molecules and thus, stabilizes the high spin form due to the breaking of hydrogen bonding networks; compared to 2 and 3, which keep their low spin state up to 400 K.

Application of space-charge electrostatic precipitator for collection of oil mist from pyrolysis gases

A novel electrostatic precipitator CAROLA® is developed for collection of fine oil mists. It operates on the principle of unipolar particle charging in the corona discharge and particle precipitation under the field of space charge. The pilot precipitator was tested at different gas temperatures. It is shown that the increase of gas temperature changes the characteristics of the corona discharge and particle size distribution, especially for droplets sub-micron droplets. The CAROLA® precipitator was used for collection of oil mist from pyrolysis gases at the HALOCLEAN® plant. The flow rate of biomass in the HALOCLEAN® plant was 15-30 kg/h. The particle mass concentration in the raw gas was over 100 g/Nm. The operation voltage of the precipitator was 10-12 kV and corona current up to 0,1 mA. Single stage electrostatic precipitator ensured mass collection efficiency 97-99,5% for pyrolysis oil mist.