Meaning selection and the subcortex: Evidence of reduced lexical ambiguity repetition effects following subcortical lesions

Recent research indicates that individuals with nonthalamic subcortical (NS) lesions call experience difficulties processing lexical ambiguities in a variety of contexts. This study examined how prior processing of a lexical ambiguity influences subsequent meaning activation in 10 individuals with NS lesions and 10 matched healthy controls. Subjects made speeded lexical decisions oil related or unrelated targets following homophone primes. Homophones were repealed with different targets biasing the same or different meanings oil the second presentation. The effects of prime-target relatedness, interstimulus interval (200 or 1250 ms), and same vs different meaning repetition were examined Both the patient and control groups showed printing when the same homophone meaning was biased oil repetition. When a different meaning was biased on the second presentation. no priming was evident in the controls, while facilitation remained present for the NS group, consistent with aberrant meaning selection and deactivation processes. These findings are discussed in terms of age and task-related repetition effects and current conceptions of frontal-subcortical involvement in cognition.

Top-down influences on lexical selection during spoken word production: A 4T fMRI investigation of refractory effects in picture naming

Spoken word production is assumed to involve stages of processing in which activation spreads through layers of units comprising lexical-conceptual knowledge and their corresponding phonological word forms. Using high-field (4T) functional magnetic resonance imagine (fMRI), we assessed whether the relationship between these stages is strictly serial or involves cascaded-interactive processing, and whether central (decision/control) processing mechanisms are involved in lexical selection. Participants performed the competitor priming paradigm in which distractor words, named from a definition and semantically related to a subsequently presented target picture, slow picture-naming latency compared to that with unrelated words. The paradigm intersperses two trials between the definition and the picture to be named, temporally separating activation in the word perception and production networks. Priming semantic competitors of target picture names significantly increased activation in the left posterior temporal cortex, and to a lesser extent the left middle temporal cortex, consistent with the predictions of cascaded-interactive models of lexical access. In addition, extensive activation was detected in the anterior cingulate and pars orbitalis of the inferior frontal gyrus. The findings indicate that lexical selection during competitor priming is biased by top-down mechanisms to reverse associations between primed distractor words and target pictures to select words that meet the current goal of speech.

Attenuated total reflection-FT-IR spectroscopic imaging of protein crystallization

Protein crystallization is of strategic and commercial relevance in the post-genomic era because of its pivotal role in structural proteomics projects. Although protein structures are crucial for understanding the function of proteins and to the success of rational drug design and other biotechnology applications, obtaining high quality crystals is a major bottleneck to progress. The major means of obtaining crystals is by massive-scale screening of a target protein solution with numerous crystallizing agents. However, when crystals appear in these screens, one cannot easily know if they are crystals of protein, salt, or any other molecule that happens to be present in the trials. We present here a method based on Attenuated Total Reflection (ATR)-FT-IR imaging that reliably identifies protein crystals through a combination of chemical specificity and the visualizing capability of this approach, thus solving a major hurdle in protein crystallization. ATR-FT-IR imaging was successfully applied to study the crystallization of thaumatin and lysozyme in a high-throughput manner, simultaneously from six different solutions. This approach is fast as it studies protein crystallization in situ and provides an opportunity to examine many different samples under a range of conditions.

Bacterial resistance to antibiotics:modified target sites

Alteration in the target sites of antibiotics is a common mechanism of resistance. Examples of clinical strains showing resistance can be found for every class of antibiotic, regardless of the mechanism of action. Target site changes often result from spontaneous mutation of a bacterial gene on the chromosome and selection in the presence of the antibiotic. Examples include mutations in RNA polymerase and DNA gyrase, resulting in resistance to the rifamycins and quinolones, respectively. In other cases, acquisition of resistance may involve transfer of resistance genes from other organisms by some form of genetic exchange (conjugation, transduction, or transformation). Examples of these mechanisms include acquisition of the mecA genes encoding methicillin resistance in Staphylococcus aureus and the various van genes in enterococci encoding resistance to glycopeptides. © 2005 Elsevier B.V. All rights reserved.

On the interaction between perceptual and response selection: neuropsychological evidence

We examined the relations between selection for perception and selection for action in a patient FK, with bilateral damage to his temporal and medial frontal cortices. The task required a simple grasp response to a common object (a cup) in the presence of a distractor (another cup). The target was cued by colour or location, and FK made manual responses. We examined the effects on performance of cued and uncued dimensions of both the target and the distractor. FK was impaired at perceptually selecting the target when cued by colour, when the target colour but not its location changed on successive trials. The effect was sensitive to the relative orientations of targets and distractors, indicating an effect of action selection on perceptual selection, when perceptual selection was weakly instantiated. The dimension-specific carry-over effect on reaching was enhanced when there was a temporal delay between a cue and the response, and it disappeared when there was a between-trial delay. The results indicate that perceptual and action selection systems interact to determine the efficiency with which actions are selected to particular objects.

Evaluating choices:the role of corpora in translation choices and target text assessment

Translation training in the university context needs to train students in the processes, in order to enhance and optimise the product as outcome of these processes. Evaluation of a target text as product has often been accused of being a subjective process, which does not easily lend itself to the type of feedback that could enable students to apply criteria more widely. For students, it often seems as though they make different inappropriate or incorrect choices every time they translate a new text, and the learning process appears unpredictable and haphazard. Within functionalist approaches to translation, with their focus on the target text in terms of functional adequacy to the intended purpose, as stipulated in the translation brief, there are guidelines for text production that can help to develop a more systematic approach not only to text production, but also to translation evaluation. In the context of a focus on user knowledge needs, target language conventions and acceptability, the use of corpora is an indispensable tool for the trainee translator. Evaluation can take place against the student's own reasoned selection process, based on hard evidence, against criteria which currently obtain in the TL and the TL culture. When trainee and evaluator work within the same guidelines, there is more scope for constructive learning and feedback.

Energy-efficient self -organization of wireless acoustic sensor networks for ground target tracking

With the developments in computing and communication technologies, wireless sensor networks have become popular in wide range of application areas such as health, military, environment and habitant monitoring. Moreover, wireless acoustic sensor networks have been widely used for target tracking applications due to their passive nature, reliability and low cost. Traditionally, acoustic sensor arrays built in linear, circular or other regular shapes are used for tracking acoustic sources. The maintaining of relative geometry of the acoustic sensors in the array is vital for accurate target tracking, which greatly reduces the flexibility of the sensor network. To overcome this limitation, we propose using only a single acoustic sensor at each sensor node. This design greatly improves the flexibility of the sensor network and makes it possible to deploy the sensor network in remote or hostile regions through air-drop or other stealth approaches. Acoustic arrays are capable of performing the target localization or generating the bearing estimations on their own. However, with only a single acoustic sensor, the sensor nodes will not be able to generate such measurements. Thus, self-organization of sensor nodes into virtual arrays to perform the target localization is essential. We developed an energy-efficient and distributed self-organization algorithm for target tracking using wireless acoustic sensor networks. The major error sources of the localization process were studied, and an energy-aware node selection criterion was developed to minimize the target localization errors. Using this node selection criterion, the self-organization algorithm selects a near-optimal localization sensor group to minimize the target tracking errors. In addition, a message passing protocol was developed to implement the self-organization algorithm in a distributed manner. In order to achieve extended sensor network lifetime, energy conservation was incorporated into the self-organization algorithm by incorporating a sleep-wakeup management mechanism with a novel cross layer adaptive wakeup probability adjustment scheme. The simulation results confirm that the developed self-organization algorithm provides satisfactory target tracking performance. Moreover, the energy saving analysis confirms the effectiveness of the cross layer power management scheme in achieving extended sensor network lifetime without degrading the target tracking performance.

Energy-Efficient Self-Organization of Wireless Acoustic Sensor Networks for Ground Target Tracking

With the developments in computing and communication technologies, wireless sensor networks have become popular in wide range of application areas such as health, military, environment and habitant monitoring. Moreover, wireless acoustic sensor networks have been widely used for target tracking applications due to their passive nature, reliability and low cost. Traditionally, acoustic sensor arrays built in linear, circular or other regular shapes are used for tracking acoustic sources. The maintaining of relative geometry of the acoustic sensors in the array is vital for accurate target tracking, which greatly reduces the flexibility of the sensor network. To overcome this limitation, we propose using only a single acoustic sensor at each sensor node. This design greatly improves the flexibility of the sensor network and makes it possible to deploy the sensor network in remote or hostile regions through air-drop or other stealth approaches. Acoustic arrays are capable of performing the target localization or generating the bearing estimations on their own. However, with only a single acoustic sensor, the sensor nodes will not be able to generate such measurements. Thus, self-organization of sensor nodes into virtual arrays to perform the target localization is essential. We developed an energy-efficient and distributed self-organization algorithm for target tracking using wireless acoustic sensor networks. The major error sources of the localization process were studied, and an energy-aware node selection criterion was developed to minimize the target localization errors. Using this node selection criterion, the self-organization algorithm selects a near-optimal localization sensor group to minimize the target tracking errors. In addition, a message passing protocol was developed to implement the self-organization algorithm in a distributed manner. In order to achieve extended sensor network lifetime, energy conservation was incorporated into the self-organization algorithm by incorporating a sleep-wakeup management mechanism with a novel cross layer adaptive wakeup probability adjustment scheme. The simulation results confirm that the developed self-organization algorithm provides satisfactory target tracking performance. Moreover, the energy saving analysis confirms the effectiveness of the cross layer power management scheme in achieving extended sensor network lifetime without degrading the target tracking performance.

Spectroscopic Studies of Fermi LAT Blazars

Blazar research offers a view to one of the most energetic physical processes known to man. The high-energy end of blazar emission has been probed by the Fermi satellite mission since 2008, and it has catalogued more than a thousand gamma- ray bright blazars. However, a large fraction of these sources have no spectroscopic classification at lower energies. In this thesis, optical spectra for sixteen Fermi blazar candidates are published. The optical spectroscopic data have been observed with the Nordic Optical Telescope on the island of La Palma, Spain, during the summer of 2015. The ALFOSC instrument was used, with exposure times from 800 to 3000 seconds per target, yielding signal- to-noise ratios from 10 to 38. All of the sixteen targets show a flat, featureless optical spectrum, characteristic to BL Lacertae objects. The spectra of two targets contain faint emission features, and faint absorption features are seen in three targets. However, none of the features could be reliably identified. Therefore all of the targets are classified as BL Lacertae objects. This classification is supported by the statistical distribution of Fermi -selected active galactic nuclei; more than half of the identified Fermi AGN are BL Lacs. However, the classification of this sample could be improved further with a new observing campaign. This is especially true for the objects with uncertain spectral features.

Investigating the role of target cell availability in the pathogenesis of feline immunodeficiency virus infection

Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, which shares many similarities with its human counterpart, human immunodeficiency virus (HIV). FIV infects its main target cell, the CD4+ T lymphocyte, via interactions with its primary receptor CD134 (an activation marker expressed on activated CD4+ T lymphocytes), and, the chemokine receptor CXCR4. According to the different ways in which FIV isolates interact with CD134, FIV may be categorised into two groups. The first group contains strains that tend to dominate during the earlier phase of infection, such as GL8 and CPG41. These strains are characterized by their requirement for an additional interaction with the second cysteine rich domain (CRD2) of the CD134 molecule and are classified as “CRD2-dependent” strains. The second group, on the other hand, contains either laboratory-adapted isolates or isolates that emerge after several years of infection, such as PPR or the GL8 variants that emerged in cats 6 years post experimental infection and were studied in this thesis. These isolates are designated “CRD2-independent” as they can infect target cells without interacting with CRD2 of the CD134 molecule. This study provides the first evidence that FIV compartmentalisation is related to FIV-CD134 usage and the tissue availability of CD134+ target cells. In tissue compartments containing high levels of CD134+ cells such as peripheral blood and lymph nodes, CRD2-dependent viruses predominated, whereas CRD2-independent viruses predominated in compartments with fewer CD134+ cells, such as the thymus. The dynamics of CD4+CD134+ T lymphocytes at different stages of FIV infection were also described. The levels of CD4+CD134+ T lymphocytes, which were very high in the early phase, gradually decreased in the later phase of infection. The dynamics of CD4+CD134+ T lymphocyte numbers appeared to correlate with FIV tropism switching, as more CRD2-independent viruses were isolated from cats in the late phase of infection. Moreover, it was observed that pseudotypes bearing Envs of CRD2-dependent variants infected CD134+ target cells more efficiently than pseudotypes bearing Envs of CRD2-independent variants, confirming the selective advantage of CRD2-dependent variants in environments with high levels of CD134+ target cells. In conclusion, this study demonstrated that target cell types and numbers, as well as their dynamics, play important roles in the selection and expansion of FIV variants within the viral quasispecies. Improved understanding of the roles of target cells in FIV transmission and pathogenesis will provide important information required for the development of an improved, more successful protective FIV vaccine and will provide insight into the development of effective vaccines against other lentiviral infections such as HIV.

Genome selection in fruit breeding: application to table grapes.

Genomic selection (GS) has recently been proposed as a new selection strategy which represents an innovative paradigm in crop improvement, now widely adopted in animal breeding. Genomic selection relies on phenotyping and high-density genotyping of a sufficiently large and representative sample of the target breeding population, so that the majority of loci that regulate a quantitative trait are in linkage disequilibrium with one or more molecular markers and can thus be captured by selection. In this study we address genomic selection in a practical fruit breeding context applying it to a breeding population of table grape obtained from a cross between the hybrid genotype D8909-15 (Vitis rupestris × Vitis arizonica/girdiana), which is resistant to dagger nematode and Pierce?s disease (PD), and ?B90-116?, a susceptible Vitis vinifera cultivar with desirable fruit characteristics. Our aim was to enhance the knowledge on the genomic variation of agronomical traits in table grape populations for future use in marker-assisted selection (MAS) and GS, by discovering a set of molecular markers associated with genomic regions involved in this variation. A number of Quantitative Trait Loci (QTL) were discovered but this method is inaccurate and the genetic architecture of the studied population was better captured by the BLasso method of genomic selection, which allowed for efficient inference about the genetic contribution of the various marker loci. The technology of genomic selection afforded greater efficiency than QTL analysis and can be very useful in speeding up the selection procedures for agronomic traits in table grapes.

ABC transporters of the A subfamily: potential prognostic markers and candidates for antibody selection from phage-display libraries for therapeutic use in Ewing sarcoma

The prognostic value of ABC transporters in Ewing sarcoma is still poorly explored and controversial. We described for the first time the impact of various ABCs on Ewing sarcoma prognosis by assessment of their gene expression in two independent cohorts of patients. Unexpected associations with favourable outcomes were observed for two ABCs of the A-subfamily, ABCA6 and ABCA7, whereas no associations with the canonical multidrug ABC transporters were identified. The ABCs of the A-subfamily are involved in cholesterol/phospholipids transportation and efflux from cells. Our clinical data support the drug-efflux independent contribution to cancer progression of the ABCAs, which has been confirmed in PDX-derived cell lines. The impact of these ABCA transporters on tumor progression seems to be mediated by lowering intracellular cholesterol, supporting the role of these proteins in lipid transport. In addition, the gene expression of ABCA6 and ABCA7 is regulated by transcription factors which control lipid metabolism: ABCA6 was induced by the binding of FoxO1/FoxO3a to its promoter and repressed by IGF1R/Akt signaling, whereas the expression of ABCA7 was regulated by p53. The data point to ABCA6 and ABCA7 as potential prognostic markers in Ewing sarcoma and suggest the IGF1/ABCA/lipid axis as an intriguing therapeutic target. Agonist monoclonal antibodies towards ABCA6/7 or inhibitors of cholesterol biosynthesis, such as statins or aminobiphoshonates, may be investigated as therapeutic options in combination with chemotherapy. Considering that no monoclonal antibodies selectively targeting extracellular domains of ABCA6/7 are available, the second part of the project has been dedicated to the generation of human antibody phage-display libraries as tools for selecting monoclonal antibodies. A novel synthetic human antibody phage-display library has been designed, cloned and characterized. The library takes advantages of the high variability of a designed naïve repertoire to be a useful tool for isolating antibodies towards all potential antigens, including the ABCAs.

Identification Of Target Genes Using Gene Expression Profile Of Granulocytes From Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.

Petroleomics By Electrospray Ionization Ft-icr Mass Spectrometry Coupled To Partial Least Squares With Variable Selection Methods: Prediction Of The Total Acid Number Of Crude Oils.

Negative-ion mode electrospray ionization, ESI(-), with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was coupled to a Partial Least Squares (PLS) regression and variable selection methods to estimate the total acid number (TAN) of Brazilian crude oil samples. Generally, ESI(-)-FT-ICR mass spectra present a power of resolution of ca. 500,000 and a mass accuracy less than 1 ppm, producing a data matrix containing over 5700 variables per sample. These variables correspond to heteroatom-containing species detected as deprotonated molecules, [M - H](-) ions, which are identified primarily as naphthenic acids, phenols and carbazole analog species. The TAN values for all samples ranged from 0.06 to 3.61 mg of KOH g(-1). To facilitate the spectral interpretation, three methods of variable selection were studied: variable importance in the projection (VIP), interval partial least squares (iPLS) and elimination of uninformative variables (UVE). The UVE method seems to be more appropriate for selecting important variables, reducing the dimension of the variables to 183 and producing a root mean square error of prediction of 0.32 mg of KOH g(-1). By reducing the size of the data, it was possible to relate the selected variables with their corresponding molecular formulas, thus identifying the main chemical species responsible for the TAN values.

Stathmin 1, A Therapeutic Target In Esophageal Carcinoma?

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