UPLC-TOF-MS for plant metabolomics: a sequential approach for wound marker analysis in Arabidopsis thaliana.

The model plant Arabidopsis thaliana was studied for the search of new metabolites involved in wound signalling. Diverse LC approaches were considered in terms of efficiency and analysis time and a 7-min gradient on a UPLC-TOF-MS system with a short column was chosen for metabolite fingerprinting. This screening step was designed to allow the comparison of a high number of samples over a wide range of time points after stress induction in positive and negative ionisation modes. Thanks to data treatment, clear discrimination was obtained, providing lists of potential stress-induced ions. In a second step, the fingerprinting conditions were transferred to longer column, providing a higher peak capacity able to demonstrate the presence of isomers among the highlighted compounds.

Comparison of naphthalene bioavailability determined by whole-cell biosensing and availability determined by extraction with Tenax

A rapid biological method for the determination of the bioavailability of naphthalene was developed and its value as an alternative to extraction-based chemical approaches demonstrated. Genetically engineered whole-cell biosensors are used to determine bioavailable naphthalene and their responses compared with results from Tenax extraction and chemical analysis. Results show a 1:1 correlation between biosensor results and chemical analyses for naphthalene-contaminated model materials and sediments, but the biosensor assay is much faster. This work demonstrates that biosensor technology can perform as well as standard chemical methods, though with some advantages including the inherent biological relevance of the response, rapid response time, and potential for field deployment. A survey of results from this work and the literature shows that bioavailability under non-equilibrium conditions nonetheless correlates well with K(oc) or K(d). A rationale is provided wherein chemical resistance is speculated to be operative.

Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial.

BACKGROUND: Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting. METHODS: This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75). Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (< or = 16% vs >16%). Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered orally once daily at a dose of 2.5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00208273. FINDINGS: All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment. During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity. The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis). INTERPRETATION: Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy. Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes. FUNDING: Novartis Oncology France.

JPEG standard uniform quantization error modeling with applications to sequential and progressive operation modes

In this paper we propose a method for computing JPEG quantization matrices for a given mean square error or PSNR. Then, we employ our method to compute JPEG standard progressive operation mode definition scripts using a quantization approach. Therefore, it is no longer necessary to use a trial and error procedure to obtain a desired PSNR and/or definition script, reducing cost. Firstly, we establish a relationship between a Laplacian source and its uniform quantization error. We apply this model to the coefficients obtained in the discrete cosine transform stage of the JPEG standard. Then, an image may be compressed using the JPEG standard under a global MSE (or PSNR) constraint and a set of local constraints determined by the JPEG standard and visual criteria. Secondly, we study the JPEG standard progressive operation mode from a quantization based approach. A relationship between the measured image quality at a given stage of the coding process and a quantization matrix is found. Thus, the definition script construction problem can be reduced to a quantization problem. Simulations show that our method generates better quantization matrices than the classical method based on scaling the JPEG default quantization matrix. The estimation of PSNR has usually an error smaller than 1 dB. This figure decreases for high PSNR values. Definition scripts may be generated avoiding an excessive number of stages and removing small stages that do not contribute during the decoding process with a noticeable image quality improvement.

Repurposing Social Tagging Data for Extraction of Domain-level Concepts

The World Wide Web, the world¿s largest resource for information, has evolved from organizing information using controlled, top-down taxonomies to a bottom up approach that emphasizes assigning meaning to data via mechanisms such as the Social Web (Web 2.0). Tagging adds meta-data, (weak semantics) to the content available on the web. This research investigates the potential for repurposing this layer of meta-data. We propose a multi-phase approach that exploits user-defined tags to identify and extract domain-level concepts. We operationalize this approach and assess its feasibility by application to a publicly available tag repository. The paper describes insights gained from implementing and applying the heuristics contained in the approach, as well as challenges and implications of repurposing tags for extraction of domain-level concepts.

Concurrent or Sequential Adjuvant Letrozole and Radiotherapy after Conservative Surgery for Early-stage Breast Cancer: Long-term Results of the Cohort Phase 2 Randomized Trial

Purpose/Objective(s): Letrozole radiosensitizes breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.Materials/Methods: The present study is registered with ClinicalTrials.gov, number NCT00208273. This Phase 2 randomized trial was undertaken in two centers in France and one in Switzerland between January 12, 2005, and February 21, 2007. One hundred fifty postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n = 75) or sequential radiotherapy and letrozole (n = 75). Randomization was open label with a minimization technique, stratified by investigational centers, chemotherapy (yes vs. no), radiation boost (yes vs. no), and value of radiation-induced lymphocyte apoptosis (#16% vs. .16%). The whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44 - 50 Gy. Letrozole was administered orally once daily at a dose of 2 - 5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks postradiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced Grade 2 or worse toxic effects of the skin and lung (functional pulmonary test and lung CT-scan). Analyses were by intention-to-treat. The long-term follow-up after 2 years was only performed in Montpellier (n = 121) and evaluated skin toxicity (clinical examination every 6 months), lung fibrosis (one CT-scan yearly), cosmetic outcome.Results: All patients were analyzed apart from 1 in the concurrent group who withdrew consent before any treatment.Within the first 2 years (n = 149), no lung toxicity was identified by CT scan and no modification from baseline was noted by the lung diffusion capacity test. Two patients in each group had Grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis [RISF]). After 2 years (n = 121), and with a median follow-up of 50 months (38-62), 2 patients (1 in each arm) presented a Grade 3 RISF. No lung toxicity was identified by CT scan. Cosmetic results (photographies) and quality of life was good to excellent. All patients who had Grade 3 subcutaneous fibrosis had an RILA value of 16% or less, irrespective of the sequence with letrozole.Conclusions:With long-term follow-up, letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy.

Influence of rootstocks and pruning times on yield and on nutrient content and extraction in 'Niagara Rosada' grapevine

The objective of this work was to evaluate the influence of rootstocks and pruning times on yield and on nutrient content and extraction by pruned branches and harvested bunches of 'Niagara Rosada' grapevine in subtropical climate. The rootstocks 'IAC 766', 'IAC 572', 'IAC 313', 'IAC 571-6', and '106-8 Mgt' were evaluated. Treatments consisted of a combination between five rootstocks and three pruning times. At pruning, fresh and dry matter mass of branches were evaluated to estimate biomass accumulation. At harvest, yield was estimated by weighing of bunches per plant. Branches and bunches were sampled at pruning and at harvest, respectively, for nutrient content analysis. Nutrient content and dry matter mass of branches and bunches were used to estimate total nutrient extraction. 'Niagara Rosada' grapevine grafted onto the 'IAC 572' rootstock had the highest yield and dry matter mass of bunches, which were significantly different from the ones observed in 'Niagara Rosada'/'IAC 313'. 'Niagara Rosada' grafted onto the 'IAC 572' rootstock extracted the largest quantity of K, P, Mg, S, Cu, and Fe, differing from 'IAC 313' and 'IAC 766' in K and P extraction, and from '106-8 Mgt' in Mg and S extraction. Winter pruning results in higher yield, dry matter accumulation by branches, and total nutrient content and extraction.

Effects of preset sequential administrations of sunitinib and everolimus on tumour differentiation in Caki-1 renal cell carcinoma.

BACKGROUND: Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus. METHODS: In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence. RESULTS: Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis. CONCLUSIONS: In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.

Embedding, Extraction and Detection of Digital Watermark in Spectral Images

Tässä diplomityössä tutkitaan tekniikoita, joillavesileima lisätään spektrikuvaan, ja menetelmiä, joilla vesileimat tunnistetaanja havaitaan spektrikuvista. PCA (Principal Component Analysis) -algoritmia käyttäen alkuperäisten kuvien spektriulottuvuutta vähennettiin. Vesileiman lisääminen spektrikuvaan suoritettiin muunnosavaruudessa. Ehdotetun mallin mukaisesti muunnosavaruuden komponentti korvattiin vesileiman ja toisen muunnosavaruuden komponentin lineaarikombinaatiolla. Lisäyksessä käytettävää parametrijoukkoa tutkittiin. Vesileimattujen kuvien laatu mitattiin ja analysoitiin. Suositukset vesileiman lisäykseen esitettiin. Useita menetelmiä käytettiin vesileimojen tunnistamiseen ja tunnistamisen tulokset analysoitiin. Vesileimojen kyky sietää erilaisia hyökkäyksiä tarkistettiin. Diplomityössä suoritettiin joukko havaitsemis-kokeita ottamalla huomioon vesileiman lisäyksessä käytetyt parametrit. ICA (Independent Component Analysis) -menetelmää pidetään yhtenä mahdollisena vaihtoehtona vesileiman havaitsemisessa.

Can resistance to trastuzumab be reversed by endocrine therapy? Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with ER-positive, HER-2 positive, advanced breast cancer: a proof-of-concept trial (SAKK 23/03)

Introduction: Trastuzumab (T) is a cornerstone in the treatment of patients with HER2-overexpressing advanced breast cancer and development of resistance to T is a major therapeutic problem. HER-2 is part of a highly interactive signaling network that may impair efficacy of endocrine therapy. A sequential treatment design was chosen in this trial to ensure complete resistance to single agent therapy before receiving both a non-steroidal aromatase inhibitor (AI) and T. Any kind of clinical activity with combined treatment of AI and T after progression of single agent treatments could indicate restoration of sensitivity as a consequence of cross-talking and networking between both pathways. Methods: Key eligibility criteria included postmenopausal patients (pts.) with advanced, measurable, HER-2 positive (assessed by FISH, ratio (≥2)), HR positive disease and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in an adjuvant or advanced setting. Pts. received standard dose T monotherapy either weekly or three-weekly in step 1 and upon disease progression, continued T in combination with letrozole in step 2. The primary endpoint was clinical benefit response (CBR: CR, PR or SD for at least 24 weeks (+/- 1 week) according to RECIST) in step 2. Results: Thirteen pts. were enrolled in five centers in Switzerland. In step 1, six pts. (46%) achieved CBR. Median time to progression (TTP) was 161 days (Range: 50 - 627). Based on data collected until the end of May 2010, CBR was observed in seven out of the eleven evaluable pts. (64%) in step 2, including one pt. with partial response. Four of the seven pts. within step 2 that achieved CBR also had CBR in step 1. Seven out of eleven pts. have documented tumor progression during step 2 treatment. Median TTP for all eleven pts. was 184 days (range 61 - 471). Mean time on study treatment (TTP in step 1 plus TTP in step 2) for pts. reaching step 2 was 380 days (range 174 - 864). Adverse events were generally mild. Conclusion: Results of this proof-of-principle trial suggest that complete resistance to both AI and T can be overcome in a proportion of pts. by combined treatment of AI and T, as all pts. served as their own control. Our results appear promising for a new treatment strategy which offers a chemotherapy-free and well-tolerated option for at least a subset of the pts. with HR positive, HER-2 positive breast cancer. Further trials will need to corroborate this finding.

Local and Global Feature Extraction for Invariant Object Recognition

Perceiving the world visually is a basic act for humans, but for computers it is still an unsolved problem. The variability present innatural environments is an obstacle for effective computer vision. The goal of invariant object recognition is to recognise objects in a digital image despite variations in, for example, pose, lighting or occlusion. In this study, invariant object recognition is considered from the viewpoint of feature extraction. Thedifferences between local and global features are studied with emphasis on Hough transform and Gabor filtering based feature extraction. The methods are examined with respect to four capabilities: generality, invariance, stability, and efficiency. Invariant features are presented using both Hough transform and Gabor filtering. A modified Hough transform technique is also presented where the distortion tolerance is increased by incorporating local information. In addition, methods for decreasing the computational costs of the Hough transform employing parallel processing and local information are introduced.

A Sequential Allocation Problem: The Asymptotic Distribution of Resources

In this paper we consider a sequential allocation problem with n individuals. The first individual can consume any amount of some endowment leaving the remaining for the second individual, and so on. Motivated by the limitations associated with the cooperative or non-cooperative solutions we propose a new approach. We establish some axioms that should be satisfied, representativeness, impartiality, etc. The result is a unique asymptotic allocation rule. It is shown for n = 2; 3; 4; and a claim is made for general n. We show that it satisfies a set of desirable properties. Key words: Sequential allocation rule, River sharing problem, Cooperative and non-cooperative games, Dictator and ultimatum games. JEL classification: C79, D63, D74.

Enzymatic technology to improve oil extraction from Caryocar brasiliense camb. (Pequi) Pulp.

The present study aims to compare yield and quality of pequi pulp oil when applying two distinct processes: in the first, pulp drying in a tray dryer at 60ºC was combined with enzymatic treatment and pressing to oil extraction; in the second, a simple process was carried out by combining sun-drying pulp and pressing. In this study, raw pequi fruits were collected in Mato Grosso State, Brazil. The fruits were autoclaved at 121ºC and stored under refrigeration. An enzymatic extract with pectinase and CMCase activities was used for hydrolysis of pequi pulp, prior to oil extraction. The oil extractions were carried out by hydraulic pressing, with or without enzymatic incubation. The oil content in the pequi pulp (45% w/w) and the physicochemical characteristic of the oil was determined according to standard analytical methods. Free fatty acids, peroxide values, iodine and saponification indices were respectively 1.46 mgKOH/g, 2.98 meq/kg, 49.13 and 189.40. The acidity and peroxide values were lower than the obtained values in commercial oil samples, respectively 2.48 mgKOH/g and 5.22 meq/kg. Aqueous extraction has presented lower efficiency and higher oxidation of unsaturated fatty acids. On the other hand, pequi pulp pressing at room temperature has produced better quality oil. However its efficiency is still smaller than the combined enzymatic treatment and pressing process. This combined process promotes cellular wall hydrolysis and pulp viscosity reduction, contributing to at least 20% of oil yield increase by pressing.