The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Open source software expectations in retail businesses of Igualada : an exploratory study

The emergence of open source software in the last years has become a common topic of study in different fields, from the most technical characteristics to the economical aspects. This paper examines the current status about the literature dealing with economics of open source and explores the uses, infrastructure and expectations of retail businesses and institutions of the town of Igualda about it. This qualitative case study finds out that the current equipment and level of uses of ICTs are low and that the current situation of the town stores is receptive to a potential introduction of open source software.

Qualité des statistiques de causes de décès: problèmes actuels et perspectives. [Quality of statistics on causes of death: current problems and perspectives].

Statistics of causes of death remain an important source of epidemiological data for the evaluation of various medical and health problems. The improvement of analytical techniques and, above all, the transformation of demographic and morbid structures of populations have prompted researchers in the field to give more importance to the quality of death certificates. After describing the data collection system presently used in Switzerland, the paper discusses various indirect estimations of the quality of Swiss data and reviews the corresponding international literature.

Disentangling the attention network test: behavioral, event related potentials, and neural source analyses.

BACKGROUND The study of the attentional system remains a challenge for current neuroscience. The "Attention Network Test" (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. RESULTS This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. CONCLUSIONS The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects.

Origin and outcome of multiple pregnancies in Bern, Switzerland, 1995-2006 and the current proposal of the Swiss parliament to revise the Swiss law of reproductive medicine: Switzerland quo vadis?

INTRODUCTION: Infertility treatments are a major source of the increase in multiple pregnancies (MPs). AIMS: The aims of the present study were (1.) to investigate the origin and maternal/neonatal outcomes of MP and (2.) to review the different measures that can be adopted to reduce these serious complications. METHODS: The study included all women with multiple births between 1 January 1995 and 31 December 2006 at the University Hospital of Bern, Switzerland. The outcomes associated with the various origins of MP (natural conception, ovarian stimulation [OS] ‒ in-vitro fertilisation [IVF-ICSI]) were analysed using a multinomial logistic regression model. An analysis of the Swiss law on reproductive medicine and its current proposed revision, as well as a literature review using Pubmed, was carried out. RESULTS: A total of 592 MP were registered, 91% (n = 537) resulted in live births. There was significantly more neonatal/maternal morbidity in MP after OS compared with natural conception and even with the IVF-ICSI group. With a policy of elective single embryo transfer (eSET), twin rates after IVF-ICSI can be reduced to <5% and triplets to <1%. CONCLUSIONS: After OS, more triplets are found and the outcome of MP is worse. MP is known to be associated with morbidity, mortality, and economic and social risks. To counteract these complications (1.) better training for physicians performing OS should be encouraged and (2.) the Swiss law on reproductive medicine needs to be changed, with the introduction of eSET policies. This would lead to a dramatic decrease in neonatal and maternal morbidity/mortality as well as significant cost reductions for the Swiss healthcare system.

Current trends in illegal drug use and drug related health problems in Switzerland.

As part of the evaluation of the Confederation's measures to reduce drug related problems, a review of available data on drug use and drug related problems in Switzerland has been conducted. Source of data included: population surveys (adults and teenagers), surveys among drug users, health statistics (drug related and AIDS related deaths, HIV case reporting, drug treatments) police statistics (denunciations for consumption). The aims of reducing the number of dependent hard drug users have been achieved where heroin is concerned. In particular, there seems to have been a decrease in the number of people becoming addicted to this substance. For all other illegal substances, especially cannabis, the trend is towards an increased use, as in many European countries. As regards dependent drug users, especially injecting drug users, progress has been made in the area of harm reduction and treatment coverage. This epidemiological assessment can be used in the discussions currently engaged about the revision of the Law governing narcotics and will be a baseline for future follow up of the situation.

Waveform inversion of crosshole georadar data: influence of source wavelet variability and the suitability of a single wavelet assumption

Waveform-based tomographic imaging of crosshole georadar data is a powerful method to investigate the shallow subsurface because of its ability to provide images of electrical properties in near-surface environments with unprecedented spatial resolution. A critical issue with waveform inversion is the a priori unknown source signal. Indeed, the estimation of the source pulse is notoriously difficult but essential for the effective application of this method. Here, we explore the viability and robustness of a recently proposed deconvolution-based procedure to estimate the source pulse during waveform inversion of crosshole georadar data, where changes in wavelet shape with location as a result of varying near-field conditions and differences in antenna coupling may be significant. Specifically, we examine whether a single, average estimated source current function can adequately represent the pulses radiated at all transmitter locations during a crosshole georadar survey, or whether a separate source wavelet estimation should be performed for each transmitter gather. Tests with synthetic and field data indicate that remarkably good tomographic reconstructions can be obtained using a single estimated source pulse when moderate to strong variability exists in the true source signal with antenna location. Only in the case of very strong variability in the true source pulse are tomographic reconstructions clearly improved by estimating a different source wavelet for each transmitter location.

Polarization strategies to improve the emission of a Si-based light source emitting at 1.55 um

We present a electroluminescence (EL) study of the Si-rich silicon oxide (SRSO) LEDs with and without Er3+ ions under different polarization schemes: direct current (DC) and pulsed voltage (PV). The power efficiency of the devices and their main optical limitations are presented. We show that under PV polarization scheme, the devices achieve one order of magnitude superior performance in comparison with DC. Time-resolved measurements have shown that this enhancement is met only for active layers in which annealing temperature is high enough (>1000 ◦C) for silicon nanocrystal (Si-nc) formation. Modeling of the system with rate equations has been done and excitation cross-sections for both Si-nc and Er3+ ions have been extracted.

Current status of a model system: the gene Gp-9 and its association with social organization in fire ants.

The Gp-9 gene in fire ants represents an important model system for studying the evolution of social organization in insects as well as a rich source of information relevant to other major evolutionary topics. An important feature of this system is that polymorphism in social organization is completely associated with allelic variation at Gp-9, such that single-queen colonies (monogyne form) include only inhabitants bearing B-like alleles while multiple-queen colonies (polygyne form) additionally include inhabitants bearing b-like alleles. A recent study of this system by Leal and Ishida (2008) made two major claims, the validity and significance of which we examine here. After reviewing existing literature, analyzing the methods and results of Leal and Ishida (2008), and generating new data from one of their study sites, we conclude that their claim that polygyny can occur in Solenopsis invicta in the U.S.A. in the absence of expression of the b-like allele Gp-9(b) is unfounded. Moreover, we argue that available information on insect OBPs (the family of proteins to which GP-9 belongs), on the evolutionary/population genetics of Gp-9, and on pheromonal/behavioral control of fire ant colony queen number fails to support their view that GP-9 plays no role in the chemosensory-mediated communication that underpins regulation of social organization. Our analyses lead us to conclude that there are no new reasons to question the existing consensus view of the Gp-9 system outlined in Gotzek and Ross (2007).

Power quality improving with virtual flux-based voltage source line converter

Line converters have become an attractive AC/DC power conversion solution in industrial applications. Line converters are based on controllable semiconductor switches, typically insulated gate bipolar transistors. Compared to the traditional diode bridge-based power converters line converters have many advantageous characteristics, including bidirectional power flow, controllable de-link voltage and power factor and sinusoidal line current. This thesis considers the control of the lineconverter and its application to power quality improving. The line converter control system studied is based on the virtual flux linkage orientation and the direct torque control (DTC) principle. A new DTC-based current control scheme is introduced and analyzed. The overmodulation characteristics of the DTC converter are considered and an analytical equation for the maximum modulation index is derived. The integration of the active filtering features to the line converter isconsidered. Three different active filtering methods are implemented. A frequency-domain method, which is based on selective harmonic sequence elimination, anda time-domain method, which is effective in a wider frequency band, are used inharmonic current compensation. Also, a voltage feedback active filtering method, which mitigates harmonic sequences of the grid voltage, is implemented. The frequency-domain and the voltage feedback active filtering control systems are analyzed and controllers are designed. The designs are verified with practical measurements. The performance and the characteristics of the implemented active filtering methods are compared and the effect of the L- and the LCL-type line filteris discussed. The importance of the correct grid impedance estimate in the voltage feedback active filter control system is discussed and a new measurement-based method to obtain it is proposed. Also, a power conditioning system (PCS) application of the line converter is considered. A new method for correcting the voltage unbalance of the PCS-fed island network is proposed and experimentally validated.

Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference.

Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the forensic community. This high-precision technology has already been applied to a broad range of forensic fields such as illicit drugs, explosives and flammable liquids, where current, routinely used techniques have limited powers of discrimination. The conclusions drawn from the majority of these IRMS studies appear to be very promising. Used in a comparative process, as in food or drug authentication, the measurement of stable isotope ratios is a new and remarkable analytical tool for the discrimination or the identification of a substance with a definite source or origin. However, the research consists mostly of preliminary studies. The significance of this 'new' piece of information needs to be evaluated in light of a forensic framework to assess the actual potential and validity of IRMS, considering the characteristics of each field. Through the isotopic study of black powder, this paper aims at illustrating the potential of the method and the limitations of current knowledge in stable isotopes when facing forensic problems.

Radio Frequency Measurement Method for Detecting Bearing Currents in Induction Motors

Induction motors are widely used in industry, and they are generally considered very reliable. They often have a critical role in industrial processes, and their failure can lead to significant losses as a result of shutdown times. Typical failures of induction motors can be classified into stator, rotor, and bearing failures. One of the reasons for a bearing damage and eventually a bearing failure is bearing currents. Bearing currents in induction motors can be divided into two main categories; classical bearing currents and inverter-induced bearing currents. A bearing damage caused by bearing currents results, for instance, from electrical discharges that take place through the lubricant film between the raceways of the inner and the outer ring and the rolling elements of a bearing. This phenomenon can be considered similar to the one of electrical discharge machining, where material is removed by a series of rapidly recurring electrical arcing discharges between an electrode and a workpiece. This thesis concentrates on bearing currents with a special reference to bearing current detection in induction motors. A bearing current detection method based on radio frequency impulse reception and detection is studied. The thesis describes how a motor can work as a “spark gap” transmitter and discusses a discharge in a bearing as a source of radio frequency impulse. It is shown that a discharge, occurring due to bearing currents, can be detected at a distance of several meters from the motor. The issues of interference, detection, and location techniques are discussed. The applicability of the method is shown with a series of measurements with a specially constructed test motor and an unmodified frequency-converter-driven motor. The radio frequency method studied provides a nonintrusive method to detect harmful bearing currents in the drive system. If bearing current mitigation techniques are applied, their effectiveness can be immediately verified with the proposed method. The method also gives a tool to estimate the harmfulness of the bearing currents by making it possible to detect and locate individual discharges inside the bearings of electric motors.

Diskreettiaikainen liukuvan moodin säätö kiinteäoksidipolttokennon DC-tasonnostossa

Huoli ympäristön tilasta ja fossiilisten polttoaineiden hinnan nousu ovat vauhdittaneet tutkimusta uusien energialähteiden löytämiseksi. Polttokennot ovat yksi lupaavimmista tekniikoista etenkin hajautetun energiantuotannon, varavoimalaitosten sekä liikennevälineiden alueella. Polttokenno on tehonlähteenä kuitenkin hyvin epäideaalinen, ja se asettaa tehoelektroniikalle lukuisia erityisvaatimuksia. Polttokennon kytkeminen sähköverkkoon on tavallisesti toteutettu käyttämällä galvaanisesti erottavaa DC/DC hakkuria sekä vaihtosuuntaajaa sarjassa. Polttokennon kulumisen estämiseksi tehoelektroniikalta vaaditaan tarkkaa polttokennon lähtövirran hallintaa. Perinteisesti virran hallinta on toteutettu säätämällä hakkurin tulovirtaa PI (Proportional and Integral) tai PID (Proportional, Integral and Derivative) -säätimellä. Hakkurin epälineaarisuudesta johtuen tällainen ratkaisu ei välttämättä toimi kaukana linearisointipisteestä. Lisäksi perinteiset säätimet ovat herkkiä mallinnusvirheille. Tässä diplomityössä on esitetty polttokennon jännitettä nostavan hakkurin tilayhtälökeskiarvoistusmenetelmään perustuva malli, sekä malliin perustuva diskreettiaikainen integroiva liukuvan moodin säätö. Esitetty säätö on luonteeltaan epälineaarinen ja se soveltuu epälineaaristen ja heikosti tunnettujen järjestelmien säätämiseen.

Perspectives for the production and usage of wood chips as a source of energy in the North-West of Russia

The development of bioenergy on the basis of wood fuels has received considerable attention in the last decades. The combination of large forest resources and reliance on fossil fuels makes the issue of wood chips usage in Russia an actual topic for the analysis. The main objective of this study is to disclose the current state and perspectives for the production of wood chips and their usage as a source of energy in the North-West of Russia. The study utilizes an integrated approach to explore the market of wood chips on the basis of comprehensive analysis of documentation and expert opinions. The analysis of wood chips market was performed for eight regions of the North-West district of Russia within two major dimensions: its current state and perspectives in the nearest five years. The results of the study show a comprehensive picture of the wood chips market, including the potential for wood chips production, the specific features of production and consumption and the perspectives for the market development within the regions of the North-West district of Russia. The study demonstrated that the market of wood chips is underdeveloped in the North-West of Russia. The findings of the work may be used by forest companies for the strategic planning.

Environmental adaptation of the source of the subbasin of Rico Stream, Monte Alto - SP, Brazil

The aim of this study was to define the photographic patterns that represent the use and occupation of the landcover of the "spring" of the Rico Stream subbasin, located at Monte Alto, state of São Paulo (SP), Brazil, for environmental adaptation regarding the Brazilian Forest Law. The mapping was performed using remote sensing techniques and visual interpretation of the World View image, followed by the digitalization of the net of drainage and vegetation (natural and agricultural) at the AutoCad software with documents and field work. The study area has 2141.53 ha and the results demonstrated that the main crop is sugarcane with 546.34 ha, followed by 251.22 ha of pastures, 191.71 ha of perennial crops, 57.31 ha of Eucalyptus and 49.52 ha of onion, confirming the advance of sugarcane culture in the region. The region has 375.04 ha of areas of permanent preservation (APPs), and of this area it was found that only 72.17 ha (19.24%) has arboreal vegetation or natural forest, and 302.87 ha of these areas need to be enriched and reforested with native vegetation from the region, according to the current legislation. The data of the area enable future proposals of models for environmental adaptation to the microbasin according to the current environmental legislation.