Solution structure of the dimerization domain of the eurkaryotic stalk P1/P2 complex reveals the structural organization of the eukaryotic stalk

Poster Presentation: abstract A01The lateral ribosomal stalk is responsible for the kingdom‐specific binding of translation factors and activation of GTP hydrolysis during protein synthesis. The eukaryotic stalk consists of the scaffold P0 protein which binds two copies of P1/P2 hetero‐dimers to form a P0(P1/P2)2 pentameric P‐complex. The structure of the eukaryotic stalk is currently not known. To provide a better understanding on the structural organization of eukaryotic stalk, we have determined the solution structure of the N‐terminal dimerization domain …postprin

Development of text mining tools for information retrieval from patents

Biomedical literature is composed of an ever increasing number of publications in natural language. Patents are a relevant fraction of those, being important sources of information due to all the curated data from the granting process. However, their unstructured data turns the search of information a challenging task. To surpass that, Biomedical text mining (BioTM) creates methodologies to search and structure that data. Several BioTM techniques can be applied to patents. From those, Information Retrieval is the process where relevant data is obtained from collections of documents. In this work, a patent pipeline was developed and integrated intoFEDER -Federación Española de Enfermedades Raras(NORTE-01-0145-FEDER-000004)info:eu-repo/semantics/publishedVersio

Speeding up Simplification of Polygonal Curves using Nested Approximations

We develop a multiresolution approach to the problem of polygonal curve approximation. We show theoretically and experimentally that, if the simplification algorithm A used between any two successive levels of resolution satisfies some conditions, the multiresolution algorithm MR will have a complexity lower than the complexity of A. In particular, we show that if A has a O(N2/K) complexity (the complexity of a reduced search dynamic solution approach), where N and K are respectively the initial and the final number of segments, the complexity of MR is in O(N).We experimentally compare the outcomes of MR with those of the optimal "full search" dynamic programming solution and of classical merge and split approaches. The experimental evaluations confirm the theoretical derivations and show that the proposed approach evaluated on 2D coastal maps either shows a lower complexity or provides polygonal approximations closer to the initial curves.Comment: 12 pages + figure

Interaction between maize ribosome-inactivating protein and ribosomes

Poster Presentation: abstract no. A11Ribosome‐inactivating proteins (RIPs) represent a group of N‐glycosidases which can cleave the N‐glycosidic bond of adenine at 23S and 28S ribosomal RNA (rRNA) of ribosome and subsequently lead to a halt of protein synthesis and cell death. Regardless to the universal rRNA target, the highly conserved catalytic residues and consensus tertiary structure of RIPs, the activity of RIPs is highly deviated. It is known …postprin

Ultrafast control of donor-bound electron spins with single detuned optical pulses

The ability to control spins in semiconductors is important in a variety of fields including spintronics and quantum information processing. Due to the potentially fast dephasing times of spins in the solid state [1-3], spin control operating on the picosecond or faster timescale may be necessary. Such speeds, which are not possible to attain with standard electron spin resonance (ESR) techniques based on microwave sources, can be attained with broadband optical pulses. One promising ultrafast technique utilizes single broadband pulses detuned from resonance in a three-level Lambda system [4]. This attractive technique is robust against optical pulse imperfections and does not require a fixed optical reference phase. Here we demonstrate the principle of coherent manipulation of spins theoretically and experimentally. Using this technique, donor-bound electron spin rotations with single-pulse areas exceeding pi/4 and two-pulses areas exceeding pi/2 are demonstrated. We believe the maximum pulse areas attained do not reflect a fundamental limit of the technique and larger pulse areas could be achieved in other material systems. This technique has applications from basic solid-state ESR spectroscopy to arbitrary single-qubit rotations [4, 5] and bang-bang control[6] for quantum computation.Comment: 15 pages, 4 figures, submitted 12/2008. Since the submission of this work we have become aware of related work: J. Berezovsky, M. H. Mikkelsen, N. G. Stoltz, L. A. Coldren, and D. D. Awschalom, Science 320: 349-352 (2008

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Feasibility Study of a Wearable Exoskeleton for Children: Is the Gait Altered by Adding Masses on Lower Limbs?

We are designing a pediatric exoskeletal ankle robot (pediatric Anklebot) to promote gait habilitation in children with Cerebral Palsy (CP). Few studies have evaluated how much or whether the unilateral loading of a wearable exoskeleton may have the unwanted effect of altering significantly the gait. The purpose of this study was to evaluate whether adding masses up to 2.5 kg, the estimated overall added mass of the mentioned device, at the knee level alters the gait kinematics. Ten healthy children and eight children with CP, with light or mild gait impairment, walked wearing a knee brace with several masses. Gait parameters and lower-limb joint kinematics were analyzed with an optoelectronic system under six conditions: without brace (natural gait) and with masses placed at the knee level (0.5, 1.0, 1.5, 2.0, 2.5 kg). T-tests and repeated measures ANOVA tests were conducted in order to find noteworthy differences among the trial conditions and between loaded and unloaded legs. No statistically significant differences in gait parameters for both healthy children and children with CP were observed in the five “with added mass” conditions. We found significant differences among “natural gait” and “with added masses” conditions in knee flexion and hip extension angles for healthy children and in knee flexion angle for children with CP. This result can be interpreted as an effect of the mechanical constraint induced by the knee brace rather than the effect associated with load increase. The study demonstrates that the mechanical constraint induced by the brace has a measurable effect on the gait of healthy children and children with CP and that the added mass up to 2.5 kg does not alter the lower limb kinematics. This suggests that wearable devices weighing 25 N or less will not noticeably modify the gait patterns of the population examined here.Cerebral Palsy International Research FoundationStavros S. Niarchos Foundatio

Patterns in blood pressure medication use in US incident dialysis patients over the first 6 months.

BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered