Differential T cell receptor photoaffinity labeling among H-2Kd restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative. Labeling of the alpha-chain correlates with J alpha segment usage.

Using a direct binding assay based on photoaffinity labeling, we studied the interaction of T cell receptor (TCR) with a Kd-bound photoreactive peptide derivative on living cells. The Kd-restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was reacted NH2-terminally with biotin and at the TCR contact residue Lys259 with photoreactive iodo, 4-azido salicylic acid (IASA) to make biotin-YIPSAEK(IASA)I. Cytotoxic T lymphocyte (CTL) clones derived from mice immunized with this derivative recognized this conjugate, but not a related one lacking the IASA group nor the parental PbCS peptide. The clones were Kd restricted. Recognition experiments with variant conjugates, lacking substituents from IASA, revealed a diverse fine specificity pattern and indicated that this group interacted directly with the TCR. The TCR of four clones could be photoaffinity labeled by biotin-YIPSAEK(125IASA)I. This labeling was dependent on the conjugates binding to the Kd molecule and was selective for the TCR alpha (2 clones) or beta chain (1 clone), or was common for both chains (1 clone). TCR sequence analysis showed a preferential usage of J alpha TA28 containing alpha chains that were paired with V beta 1 expressing beta chains. The TCR that were photoaffinity labeled at the alpha chain expressed these J alpha and V beta segments. The tryptophan encoded by the J alpha TA28 segment is rarely found in other J alpha segments. Moreover, we show that the IASA group interacts preferentially with tryptophan in aqueous solution. We thus propose that for these CTL clones, labeling of the alpha chain occurs via the J alpha-encoded tryptophan residue.

Diagnostic Accuracy of (18)F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis.

RATIONALE AND OBJECTIVES: To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. METHODS AND MATERIALS: A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. RESULTS: Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.

The use of expert systems on the differential diagnosis of urinary incontinence

The differential diagnosis of urinary incontinence classes is sometimes difficult to establish. As a rule, only the results of urodynamic testing allow an accurate diagnosis. However, this exam is not always feasible, because it requires special equipment, and also trained personnel to lead and interpret the exam. Some expert systems have been developed to assist health professionals in this field. Therefore, the aims of this paper are to present the definition of Artificial Intelligence; to explain what Expert System and System for Decision Support are and its application in the field of health and to discuss some expert systems for differential diagnosis of urinary incontinence. It is concluded that expert systems may be useful not only for teaching purposes, but also as decision support in daily clinical practice. Despite this, for several reasons, health professionals usually hesitate to use the computer expert system to support their decision making process.

Protocol de classificació inicial

La classificació inicial dels penats és transcendental pel fet que representa la primera proposta o disseny de tractament de l’intern, i constitueix la primera valoració del risc del subjecte. La intenció de la recerca ha estat, doncs, establir un model orientatiu d’entrevista de classificació inicial, la valoració dels aspectes significatius del risc i, de resultes, produir una guia o model d’informe, per tal d’homogeneïtzar i dotar el col·lectiu de pautes comunes d’actuació. Aquest objectiu s’ha tractat d’assolir cercant l’equilibri entre la qualitat i la simplicitat i essent conscients que el document final ha de ser una eina operativa i facilitadora de la tasca professional. El document produït pretén establir pautes d’actuació de mínims que garanteixin una uniformitat en la valoració i una aportació bàsica de dades rellevants a les autoritats administratives o judicials que han de resoldre en diferents instàncies aspectes relatius a la classificació inicial dels penats. El document s’acompanya de material d’avaluació que, tot i no estar dissenyat específicament per a poblacions penitenciàries, per les seves característiques de brevetat i simplicitat de passació i d’interpretació, pot resultar molt pràctic per aprofundir en algunes qüestions especifiques de l’avaluació quan sigui necessari.

Differential proteoglycan expression in two spinal cord regions after dorsal root injury.

Dorsal root injury leads to reactive gliosis in the spinal cord dorsal root entry zone and dorsal column, two regions that undergo Wallerian degeneration, but have distinct growth-inhibitory properties. This disparity could in part be due to differences in the number of degenerating sensory fibers, differences in glial cell activation, and/or to differential expression of growth-inhibitory molecules such as chondroitin sulfate proteoglycans. Laser capture microdissection of these two spinal cord white matter regions, followed by quantitative analysis of mRNA expression by real-time PCR, revealed that glial marker transcripts were differentially expressed post-injury and that the chondroitin sulfate proteoglycans Brevican and Versican V1 and V2 were preferentially up-regulated in the dorsal root entry zone, but not the dorsal column. These results indicate that reactive gliosis differs between these two regions and that Brevican and Versican are potential key molecules participating in the highly inhibitory properties of the dorsal root entry zone.

A short motif in Drosophila SECIS Binding Protein 2 provides differential binding affinity to SECIS RNA hairpins

Selenoproteins contain the amino acid selenocysteine which is encoded by a UGA Sec codon. Recoding UGA Sec requires a complex mechanism, comprising the cis-acting SECIS RNA hairpin in the 3′UTR of selenoprotein mRNAs, and trans-acting factors. Among these, the SECIS Binding Protein 2 (SBP2) is central to the mechanism. SBP2 has been so far functionally characterized only in rats and humans. In this work, we report the characterization of the Drosophila melanogaster SBP2 (dSBP2). Despite its shorter length, it retained the same selenoprotein synthesis-promoting capabilities as the mammalian counterpart. However, a major difference resides in the SECIS recognition pattern: while human SBP2 (hSBP2) binds the distinct form 1 and 2 SECIS RNAs with similar affinities, dSBP2 exhibits high affinity toward form 2 only. In addition, we report the identification of a K (lysine)-rich domain in all SBP2s, essential for SECIS and 60S ribosomal subunit binding, differing from the well-characterized L7Ae RNA-binding domain. Swapping only five amino acids between dSBP2 and hSBP2 in the K-rich domain conferred reversed SECIS-binding properties to the proteins, thus unveiling an important sequence for form 1 binding.

Geometry-based demosaicking

Demosaicking is a particular case of interpolation problems where, from a scalar image in which each pixel has either the red, the green or the blue component, we want to interpolate the full-color image. State-of-the-art demosaicking algorithms perform interpolation along edges, but these edges are estimated locally. We propose a level-set-based geometric method to estimate image edges, inspired by the image in-painting literature. This method has a time complexity of O(S) , where S is the number of pixels in the image, and compares favorably with the state-of-the-art algorithms both visually and in most relevant image quality measures.

Differential Gene Expression between Fall- and Spring-Run Chinook Salmon Assessed by Long Serial Analysis of Gene Expression

Of all Pacific salmonids, Chinook salmon Oncorhynchus tshawytscha display the greatest variability in return times to freshwater. The molecular mechanisms of these differential return times have not been well described. Current methods, such as long serial analysis of gene expression (LongSAGE) and microarrays, allow gene expression to be analyzed for thousands of genes simultaneously. To investigate whether differential gene expression is observed between fall- and spring-run Chinook salmon from California's Central Valley, LongSAGE libraries were constructed. Three libraries containing between 25,512 and 29,372 sequenced tags (21 base pairs/tag) were generated using messenger RNA from the brains of adult Chinook salmon returning in fall and spring and from one ocean-caught Chinook salmon. Tags were annotated to genes using complementary DNA libraries from Atlantic salmon Salmo salar and rainbow trout O. mykiss. Differentially expressed genes, as estimated by differences in the number of sequence tags, were found in all pairwise comparisons of libraries (freshwater versus saltwater = 40 genes; fall versus spring = 11 genes: and spawning versus nonspawning = 51 genes). The gene for ependymin, an extracellular glycoprotein involved in behavioral plasticity in fish, exhibited the most differential expression among the three groupings. Reverse transcription polymerase chain reaction analysis verified the differential expression of ependymin between the fall- and spring-run samples. These LongSAGE libraries, the first reported for Chinook salmon, provide a window of the transcriptional changes during Chinook salmon return migration to freshwater and spawning and increase the amount of expressed sequence data.

Differential contribution of transcription factors to Arabidopsis thaliana defense against Spodoptera littoralis

In response to insect herbivory, Arabidopsis plants activate the synthesis of the phytohor- mone jasmonate-isoleucine, which binds to a complex consisting of the receptor COI1 and JAZ repressors. Upon proteasome-mediated JAZ degradation, basic helix-loop-helix tran- scription factors (TFs) MYC2, MYC3, and MYC4 become activated and this results in the expression of defense genes. Although the jasmonate (JA) pathway is known to be essen- tial for the massive transcriptional reprogramming that follows herbivory, there is however little information on other TFs that are required for defense against herbivores and whether they contribute significantly to JA-dependent defense gene expression. By transcriptome profiling, we identified 41TFs that were induced in response to herbivory by the generalist Spodoptera littoralis. Among them, nine genes, including WRKY18, WRKY40, ANAC019, ANAC055, ZAT10, ZAT12, AZF2, ERF13, and RRTF1, were found to play a significant role in resistance to S. littoralis herbivory. Compared to the triple mutant myc234 that is as sensitive as coi1-1 to herbivory, knockout lines of these nine TFs were only partially more sensitive to S. littoralis but, however, some displayed distinct gene expression changes at the whole-genome level. Data thus reveal that MYC2, MYC3, and MYC4 are master regu- lators of Arabidopsis resistance to a generalist herbivore and identify new genes involved in insect defense.

Differential regulation of vascular endothelial growth factor expression by peroxisome proliferator-activated receptors in bladder cancer cells.

The growth of any solid tumor depends on angiogenesis. Vascular endothelial growth factor (VEGF) plays a prominent role in vesical tumor angiogenesis regulation. Previous studies have shown that the peroxisome proliferator-activated receptor gamma (PPARgamma) was involved in the angiogenesis process. Here, we report for the first time that in two different human bladder cancer cell lines, RT4 (derived from grade I tumor) and T24 (derived from grade III tumor), VEGF (mRNA and protein) is differentially up-regulated by the three PPAR isotypes. Its expression is increased by PPARalpha, beta, and gamma in RT4 cells and only by PPARbeta in T24 cells via a transcriptional activation of the VEGF promoter through an indirect mechanism. This effect is potentiated by an RXR (retinoid-X-receptor), selective retinoid LG10068 providing support for a PPAR agonist-specific action on VEGF expression. While investigating the downstream signaling pathways involved in PPAR agonist-mediated up-regulation of VEGF, we found that only the MEK inhibitor PD98059 reduced PPAR ligand-induced expression of VEGF. These data contribute to a better understanding of the mechanisms by which PPARs regulate VEGF expression. They may lead to a new therapeutic approach to human bladder cancer in which excessive angiogenesis is a negative prognostic factor.

La Traducció de l'humor en "Allo", Allo! : proposta d'una classificació

Aquest treball presenta, a través de l’anàlisi de la traducció de l’humor al català i al castellà de la sèrie britànica ’Allo’Allo!, la classificació que se’n deriva de diferents tipus d’acudits, estratègies i solucions. També valida aquesta classificació com a eina per estudiar l’estil d’un o més doblatges d’un text audiovisual on l’humor és prioritari així com per valorar-ne l’efectivitat. Sobre el corpus inicial d’aquells acudits basats en algun tret lingüístic o cultural no compartit per la llengua o cultura d’arribada, s’ha creat una classificació en quatre nivells que permet una anàlisi quantitativa d’un estil de traducció concret (dins de cada nivell o transversalment) i, a la vegada, la comparació entre dos estils diferents. El primer nivell analitza el tipus d’acudit al text original; el segon, la relació entre aquest i el text meta; el tercer, en quin tipus d’acudit s’ha materialitzat aquesta relació; i, el quart, la seva efectivitat.

Classificació de sons percussius amb un model generatiu

El treball que presentem a continuació desenvolupa un marc teòric i pràctic per a l'avaluació i estudi d'un model generatiu aplicat a tasques discriminatives de senyals sonores sense component harmònica. El model generatiu està basat en la construcció de l'anomenada deep belief network, un tipus de xarxa neuronal generativa que permet realitzar tasques de classificació i regressió com també de reconstrucció dels seus estats interns.A partir de l'anàlisi realitzada hem pogut obtenir resultats en classificació aparellats amb els resultats de l'estat de l'art de classificadors de sons inharmònics. Tot i no establir una clara superioritat envers altres mètodes, el present treball ha permés desenvolupar una anàlisi per almodel avaluat amb moltes possibilitats de millora en un futur per altres treballs. Al llarg del treball es demostra la seva eficàcia en tasques discriminatives, com també la capacitat de reduir la dimensionalitat de les dades d'entrada al model i les possibilitats de reconstruir els seus estats interns per a obtenir unes sortides de dades de la xarxa similars a les entrades de descriptors.El desenvolupament centrat en la deep belief network ens ha permés construir un entorn unificat d'avaluació de diferents mètodes d'aprenentatge, construcció i adequació de diferents descriptors sonors i una posterior visualització d'estats interns del mateix, que han possibilitat una avaluaciócomparativa i unificada respecte altres mètodes classificadors de l'estat de l'art. També ens ha permés desenvolupar una implementació en un llenguatge d'alt nivell, que ha reportat més significància per a l'enteniment i anàlisi del model avaluat, amb una argumentació més sòlida.Els resultats i l'anàlisi que reportem són significatius i positius per al model avaluat, i degut a la poca literatura existent en el camp de classificació de sons inharmònics com els sons percussius,creiem que és una aportació interessant i significativa per al camp en el que s'engloba el treball.

Asymmetric and differential gene introgression at a contact zone between two highly divergent lineages of field voles (Microtus agrestis).

Secondary contact zones have the potential to shed light on the mode and rate at which reproductive isolation accumulates during allopatric speciation. We investigated the population genetics of a contact zone between two highly divergent lineages of field voles (Microtus agrestis) in the Swiss Jura mountains. To shed light on the processes underlying introgression, we used maternally, paternally, and bi-parentally inherited markers. Though the two lineages maintained a strong genetic structure, we found some hybrids and evidence of gene flow. The extent of introgression varied with the mode of inheritance, being highest for mtDNA and absent for the Y chromosome. In addition, introgression was asymmetric, occurring only from the Northern to the Southern lineage. Both patterns seem parsimoniously explained by neutral processes linked to differences in effective sizes and sex-biased dispersal rates. The lineage with lower effective population size was also the more introgressed, and the mode-of-inheritance effect correlated with the male-biased dispersal rate of microtine rodents. We cannot exclude, however, that Haldane's effect contributed to the latter, as we found a marginally significant deficit in males (the heterogametic sex) among hybrids. We propose a possible demographic scenario to account for the patterns documented, and empirical extensions to further investigate this contact zone.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.