CLAP: A web-server for automatic classification of proteins with special reference to multi-domain proteins

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/.

IMAGE DENOISING IN MULTIPLICATIVE NOISE

We address the problem of denoising images corrupted by multiplicative noise. The noise is assumed to follow a Gamma distribution. Compared with additive noise distortion, the effect of multiplicative noise on the visual quality of images is quite severe. We consider the mean-square error (MSE) cost function and derive an expression for an unbiased estimate of the MSE. The resulting multiplicative noise unbiased risk estimator is referred to as MURE. The denoising operation is performed in the wavelet domain by considering the image-domain MURE. The parameters of the denoising function (typically, a shrinkage of wavelet coefficients) are optimized for by minimizing MURE. We show that MURE is accurate and close to the oracle MSE. This makes MURE-based image denoising reliable and on par with oracle-MSE-based estimates. Analogous to the other popular risk estimation approaches developed for additive, Poisson, and chi-squared noise degradations, the proposed approach does not assume any prior on the underlying noise-free image. We report denoising results for various noise levels and show that the quality of denoising obtained is on par with the oracle result and better than that obtained using some state-of-the-art denoisers.

自由曲面激光强化的轨迹优化研究

根据激光强化的工艺特性,从优化的角度出发,提出了一种基于平行截面法的改进算法。首先通过分析光斑的平均离焦量与光斑覆盖域曲率的关系,得到用自由曲面最大主曲率表示的工艺所允许的最大光斑尺寸公式;进而通过轨迹样本点分析的方式,得到统计平均的相邻平行截面间距。该方法综合考虑光斑大小、光斑间距、轨迹排距等多种因素,相较于一般的轨迹规划算法,能在保证加工效果的基础上有效提高加工效率。最后给出了一个算例,这一方法被用于汽车门板局部的激光强化加工轨迹规划,取得了良好的效果

Efecto del asocio de frijol común (Phaseolus vulgaris L.) en el crecimiento, desarrollo y rendimiento del cafe (Coffea arabica L) y su influencia sobre las malezas

Este trabajo experimental fue llevado a cabo con el objetivo de evaluar crecimiento, desarrollo y rendimiento del cultivo del café (Coffea arábica L.) sembrando frijol (Phasheolus vulgaris L.) en las calles de café, al mismo tiempo determinar el efecto que tengan las malezas de dicho cultivo sobre el café, y que el frijol sirva de cobertura viva para el café y coma fuente de ingreso económico y alimenticio para el agricultor. El trabajo fue realizado en el Centro Experimental de café del Pacifico (C.E.C.P.) jardín Botánico (Masatepe) durante las dos épocas de siembra para el frijol, y la cosecha anual de café (Dic-Ene) de 1992. Este ensayo se estableció con las variedades. Rev-81 para frijol y catuai amarillo para el café, este tiene una edad de 5 años. El frijol fue sembrado en las calles de café de manera tradicional con el propósito de aprovechar esa área disponible. No hubo diferencia estadística significativa en cuanto al crecimiento, desarrollo y rendimiento del café, por lo que se deduce que el frijol (P. vulgaris) no ejerce efecto negativo alguno sobre el café, lo cual indica que el cultivo en asocio no perjudica la cosecha del café por lo que se recomienda llevar a cabo esta práctica en los primeros alias de edad del café ya que no perjudica el espaciamiento de siembra.

Influencia de la rotación de cultivo y control de malezas sobre la cenosis y el crecimiento, desarrollo y rendimiento del cultivo de la soya (Glycine max (L) Merr) cv. cristalina y el cultivo del sorgo (Sorghum bicolor (L) Moench)

Se estudió la influencia de tres métodos de control de malezas en cinco rotaciones de cultivo sobre la dinámica de asociaciones de malezas y el crecimiento y desarrollo de los cultivos. El ensayo se inició en postrera de 1992 en la Hacienda "Las Mercedes" Managua, considerando en este trabajo los resultados de la siembra de primera de 1992. Se evaluó las rotaciones sorgo-sorgo, maíz-sorgo, maíz-soya, pepino-soya y pepino-sorgo y los métodos de control químico, control por período crítico y control por limpia periódica. Los resultados demuestran que el control limpia periódica efectuó un control satisfactorio de las malezas, mientras que los controles período crítico y químico fueron insuficientes, debido a que predominaban las especies monocotiledóneas como: R. cochinchinensis, de competitividad alargada y tardía así como C. rotundus y de especies dicotiledóneas como: K. maxima. Las rotaciones influyen sobre el nivel de enmalezamiento, siendo más bajo en la rotación sorgo-sorgo y pepino-soya que en las demás rotaciones. En cuanto a rendimiento los mejores resultados se obtuvieron en la rotación pepino-sorgo con 3560.330 kg/ha de sorgo y pepino-soya con 2193 kg/ha de soya debido a que el cultivo ejerció un mayor control sobre las maleza.

Teología, 1989, Tomo XXVI nº 054 (número completo)

Las “juntas eclesiásticas” durante el episcopado de Fray Juan de Zumarraga (1528-1548). Algunas precisiones históricas / Fernando Gil -- María, la mujer y la Iglesia: los tres nombres de la humanidad redimida / Antonio Marino -- La mujer en la Iglesia. Aspectos pastorales / Gerardo T. Farrell -- La iniciación cristiana hoy en América Latina. Problemáticas, desafíos y perspectivas -- Crónica de la facultad -- Notas bibliográficas -- Índice Volumen XXVI

Aspectos institucionais da política monetária

Consultoria Legislativa - Área VII - Sistema Financeiro, Direito Comercial, Direito Econômico, Defesa do Consumidor.

Activation of violaxanthin cycle in darkness is a common response to different abiotic stresses : a case study in Pelvetia canaliculata

Background: In the violaxanthin (V) cycle, V is de-epoxidized to zeaxanthin (Z) when strong light or light combined with other stressors lead to an overexcitation of photosystems. However, plants can also suffer stress in darkness and recent reports have shown that dehydration triggers V-de-epoxidation in the absence of light. In this study, we used the highly stress-tolerant brown alga Pelvetia canaliculata as a model organism, due to its lack of lutein and its non-photochemical quenching independent of the transthylakoidal-ΔpH, to study the triggering of the V-cycle in darkness induced by abiotic stressors. Results: We have shown that besides desiccation, other factors such as immersion, anoxia and high temperature also induced V-de-epoxidation in darkness. This process was reversible once the treatments had ceased (with the exception of heat, which caused lethal damage). Irrespective of the stressor applied, the resulting de-epoxidised xanthophylls correlated with a decrease in Fv/Fm, suggesting a common function in the down-regulation of photosynthetical efficiency. The implication of the redox-state of the plastoquinone-pool and of the differential activity of V-cycle enzymes on V-de-epoxidation in darkness was also examined. Current results suggest that both violaxanthin de-epoxidase (VDE) and zeaxanthin-epoxidase (ZE) have a basal constitutive activity even in darkness, being ZE inhibited under stress. This inhibition leads to Z accumulation. Conclusion: This study demonstrates that V-cycle activity is triggered by several abiotic stressors even when they occur in an absolute absence of light, leading to a decrease in Fv/Fm. This finding provides new insights into an understanding of the regulation mechanism of the V-cycle and of its ecophysiological roles.

Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells

Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.

Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

Background: The adult central nervous system (CNS) contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin(+) Sox2(+) neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium). -- Results: Here we report the isolation and long term propagation of another population of Nestin(+) cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin). These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. -- Conclusion: Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Depletion of the heaviest stable N isotope is associated with NH4 +/NH3 toxicity in NH4 +-fed plants

Background: In plants, nitrate (NO(3)(-)) nutrition gives rise to a natural N isotopic signature (delta(15)N), which correlates with the delta(15)N of the N source. However, little is known about the relationship between the delta(15)N of the N source and the (14)N/(15)N fractionation in plants under ammonium (NH(4)(+)) nutrition. When NH(4)(+) is the major N source, the two forms, NH(4)(+) and NH(3), are present in the nutrient solution. There is a 1.025 thermodynamic isotope effect between NH(3) (g) and NH(4)(+)(aq) which drives to a different delta(15)N. Nine plant species with different NH(4)(+)-sensitivities were cultured hydroponically with NO(3)(-) or NH(4)(+) as the sole N sources, and plant growth and delta(15)N were determined. Short-term NH(4)(+)/NH(3) uptake experiments at pH 6.0 and 9.0 (which favours NH(3) form) were carried out in order to support and substantiate our hypothesis. N source fractionation throughout the whole plant was interpreted on the basis of the relative transport of NH(4)(+) and NH(3). -- Results: Several NO(3)(-)-fed plants were consistently enriched in (15)N, whereas plants under NH(4)(+) nutrition were depleted of (15)N. It was shown that more sensitive plants to NH(4)(+) toxicity were the most depleted in (15)N. In parallel, N-deficient pea and spinach plants fed with (15)NH(4)(+) showed an increased level of NH(3) uptake at alkaline pH that was related to the (15)N depletion of the plant. Tolerant to NH(4)(+) pea plants or sensitive spinach plants showed similar trend on (15)N depletion while slight differences in the time kinetics were observed during the initial stages. The use of RbNO(3) as control discarded that the differences observed arise from pH detrimental effects. -- Conclusions: This article proposes that the negative values of delta(15)N in NH(4)(+)-fed plants are originated from NH(3) uptake by plants. Moreover, this depletion of the heavier N isotope is proportional to the NH(4)(+)/NH(3) toxicity in plants species. Therefore, we hypothesise that the low affinity transport system for NH(4)(+) may have two components: one that transports N in the molecular form and is associated with fractionation and another that transports N in the ionic form and is not associated with fractionation.

Identification of a biomarker panel for colorectal cancer diagnosis

Background: Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60- mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality–lost values imputation, probes quality, data smoothing and intraclass variability filtering–the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Coastal engineering investigation at Jupiter Inlet, Florida

A fixed-bed hydraulic model of Jupiter Inlet, Florida, was constructed for the purpose of testing measures designed to remedy problems of sediment erosion and deposition in the inlet area. Both tide-induced flows as well as waves were simulated in the model which was built on an undistorted scale of 1:49. Model verification was based on prototype measurements of waves, tides and currents. Results have been interpreted in terms of the influence of various proposed remedial schemes on flow velocity magnitude, distribution and wave height at various locations within the study area. A stability parameter has been utilized for evaluating the degree of sediment erosion or deposition at a given location. Various structural solutions were examined in the model. It is proposed that, in the initial phase of solution implementation, sediment removal/nourishment methods be used primarily to mitigate the existing problems. New structures, as per model test results, should be installed under subsequent phases, only if sediment management procedures do not prove to be adequate. The currently followed procedure of periodic sand trap dredging may be extended to include the new dredging/nourishment requirements. (PDF contains 245 pages.)