INNOVATIVE BIOSTATISTICAL AND BIOINFORMATIC APPROACHES IN THE ANALYSIS OF BREAST CANCER: COMPETING RISK SURVIVAL ANALYSIS THROUGH PSEUDO-VALUES AND COMPREHENSIVE EVALUATION OF METHODS FOR THE TUMOR MICROENVIRONMENT DISSECTION AVAILABLE AT THE PRESENT DAY.

Since my personal original background was quite distant from the statistical bioinformatic approaches for data analysis, having a master degree in Sanitary Biotechnology and Molecular Medicine, my PhD fellowship was spent in building my skills in this field while studying and trying to contribute to the development of biostatistical and bioinformatic approaches to be applied in clinic, with a special focus on oncology, in the optic to contribute to the field of personalized medicine. Personalized medicine is indeed the ultimate goal for life sciences, particularly for oncology, and, in my opinion, a key aspect of the future wellness of humanity. Personalized medicine is the idea of developing the ability to identify the best therapeutic strategy for each unique person and its efficacy relies on having accurate diagnostic tests that identify patients who can benefit from targeted therapies. A striking example consists in the determination of the overexpression of the human epidermal growth factor receptor type 2 (HER2) in the routinely diagnosis of Breast Cancer (BC). HER2 is indeed associated with a worse prognosis but also predicts a better response to the medication trastuzumab; a test for HER2 was approved along with the drug (as a \u201ccompanion diagnostic\u201d) so that clinicians can better target patients' treatment. My thesis is composed by the description of the two projects that have mainly characterized my fellowship. Both projects rely on breast cancer (BC) and the objective of understanding the effects of chronic low inflammation, which has been studied in my projects as the leucocyte infiltration and the body mass index. The focus on BC derives from a practical aspect and an epidemiological aspect. The practical aspect consists on the fact that my group is part of a European research group, led by Christine Desmedt from Belgium, which allowed me to obtain unique data and to interact with experts of BC and bioinformatics from different countries. The epidemiological aspect is represented by the fact that breast cancer is actually a hot topic, being the second most common cancer worldwide and the first among women, but still open to investigations, since the complexity and variability of BC, reflected both at histopathological and molecular level, have proven challenging to classify and therefore to effectively treat to the present day. The first project presented, the tumor microenvironment (TME) dissection project, occupied the first part of my fellowship and was focused on the managing of an enormous quantity of data in order to compare different tools and approaches used to analyze breast cancer. This project consisted in a big European collaboration which tried to establish the reliability of bioinformatic tools in retrieving the TME composition by analyzing bulk transcriptome and methylome and comparing the obtained results to standard approaches, as the pathologist evaluation, and emerging methods, as digital image analysis. This project led to the preparation of a paper, which is currently under submission, under the supervision of Christine Desmedt, the leader of this breast cancer research group, and Elia Biganzoli, my supervisor and member of the cited group. The second project presented, the competing risk analysis through pseudo-values project, which characterized the third year of my PhD, is more focused on the statistical aspects of clinical data analysis and represent the arrival point of my studies of statistical methodology. The project consisted in the exploration of a forefront approach to the analysis of survival data based on pseudo-values, which has the desirable feature to generate measures with a clear and direct interpretation at a clinical level, becoming an invaluable tool for clinical decision making. This project represents a first step in a longer-term project that will led to the preparation of several papers in the future

Tropospheric ozone (TOR) trend over three major inland Indian cities: Delhi, Hyderabad and Bangalore

An analysis of tropospheric column ozone using the NASA Langley TOR data during 1979-2005 has been done to investigate the trend over major Indian cities Delhi, Hyderabad and Bangalore. India was under social democratic-based policies before 1990s. Economic Liberalization began in nineties which lead to a significant growth in industrial, energy and transport sectors in major cities. Our analysis shows that there is a systematic increase in the number of months with higher tropospheric ozone values after 1990. A comparison of TOR climatology before and after 1990 over these cities shows evidence of increase in the tropospheric ozone after 1990. Trend obtained from the model shows significant change during monsoon over Delhi and during pre-monsoon and post-monsoon over Hyderabad and Bangalore. The present analysis using TOR technique demonstrates the TOR potential to detect changes in tropospheric ozone over large cities which are impacted by large anthropogenic pollution

Linear Compressor Discharge Manifold Design For High Thermal Efficiency

In the design of hermetic compressors for household refrigeration, one important part of the overall efficiency of the machine comes from a good thermal efficiency of the discharge manifold. It is desired that the heat generated during the compression process and accumulated by the gas in the discharge chamber does not return to the compression chamber walls. If not, this heat returns to the pump, reducing volumetric efficiency. Current technologies like on/off and variable velocity compressors, normally make use of metallic parts in the discharge chamber, such parts having high thermal conduction coefficients making them less efficient. Linear compressor technology, together with the non-use of oil allows the improvement of the discharge manifold system, increasing the thermal insulation of the heat from discharge chamber to compression chamber, improving efficiency. This article aims to show the development of this improved discharge system, tests performed, and results obtained

80/20 Principle: Application in Manufacturing Companies

Responding to the request of a company in pushing the income statement in profit, the authors of this article propose to apply to the products contribution margin the 80/20 principl

Thermal connection and vibrational isolation: an elegant solution for two problems

Schenberg is a detector of gravitational waves resonant mass type, with a central frequency of operation of 3200 Hz. Transducers located on the surface of the resonating sphere, according to a distribution half-dodecahedron, are used to monitor a strain amplitude. To improve the performance of the detector it is essential to decrease the temperature, then it will be cooled down, this temperature could reach as low as 50 mK. This refrigerator produces vibration noise that could compromise the performance of Schenberg detector. In this work we the study such vibration noise and how it could be minimized proposing a new connection from the dilution refrigerator to the sphere suspension. The vibration attenuation is studied by finite element modeling (FEM) and an attenuation higher than 1024 is found, higher enough to note compromise the performance of Schenberg detector.Sao Paulo Federal Institute Rua Pedro Vicente 625, 01109-010 Sao Paulo, SP, BrazilFederal University of Sao Paulo, Department of Exact and Earth Sciences Rua Sao Nicolau 120, 09913-030 Diadema, SP, BrazilINPE Astrophysics Division, Sao Jose dos Campos, SP, 12227-010, BrazilFederal University of Sao Paulo, Department of Exact and Earth Sciences Rua Sao Nicolau 120, 09913-030 Diadema, SP, BrazilWeb of Scienc

Linear Compressor Suction Valve Optimization

Design of hermetic compressors for household refrigeration follows a common sequence that considers an initial concept, normally based on existing families. Those are then upgraded with new features, aiming improvements in efficiency, sound quality or even cost reduction. Common compressors have a cylinder head that carries discharge and suction valve. In a new and compact designs for linear compressor suction valve is placed on the top of the piston, requiring new shapes in order to make it possible to satisfy, gas flow, fatigue and dynamics requirements. This article aims to present the use of optimization procedure used to develop the suction valve design for a linear compressor, the results obtained with the optimization process, and final results in compressor, in terms of performance and noise

Lake-atmosphere interactions at Alqueva reservoir : a case study in the summer of 2014

The study of lake-atmosphere interactions was the main purpose of a 2014 summer experiment at Alqueva reservoir in Portugal. Near-surface fluxes of momentum, heat and mass [water vapour (H2O) and carbon dioxide (CO2)] were obtained with the new Campbell Scientific's IRGASON Integrated Open-Path CO2/H2O Gas Analyser and 3D Sonic Anemometer between 2 June and 2 October. On average, the reservoir was releasing energy in the form of sensible and latent heat flux during the study period. At the end of the 75 d, the total evaporation was estimated as 490.26 mm. A high correlation was found between the latent heat flux and the wind speed (R = 0.97). The temperature gradient between air and water was positive between 12 and 21 UTC, causing a negative sensible heat flux, and negative during the rest of the day, triggering a positive sensible heat flux. The reservoir acted as a sink of atmospheric CO2 with an average rate of -0.026 mg m(-2) s(-1). However, at a daily scale we found an unexpected uptake between 0 and 9 UTC and almost null flux between 13 and 19 UTC. Potential reasons for this result are further discussed. The net radiation was recorded for the same period and water column heat storage was estimated using water temperature profiles. The energy balance closure for the analysed period was 81%. In-water solar spectral downwelling irradiance profiles were measured with a new device allowing measurements independent of the solar zenith angle, which enabled the computation of the attenuation coefficient of light in the water column. The average attenuation coefficient for the photosynthetically active radiation spectral region varied from 0.849 +/- 0.025 m(-1) on 30 July to 1.459 +/- 0.007 m(-1) on 25 September.Peer reviewe

Assessment of Injuries Caused by Anastrepha fraterculus (Wied.) (Diptera: Tephritidae) on the Incidence of Bunch Rot Diseases in Table Grape.

Resumo: Anastrepha fraterculus (. Wied) é a principal praga de uvas de mesa (Vitis vinifera) na Região Sul do Brasil. Neste estudo, o objetivo foi investigar o efeito da punção de frutas por fêmeas adultas e infestação larvária por A. fraterculus na ocorrência da doença podridões na uva (cultivar "Itália"). Abstract: Anastrepha fraterculus (Wied.) is the main insect pest of table grapes (Vitis vinifera) in the Southern Region of Brazil. In this study, we aimed to investigate the effect of fruit puncturing by adult females and larval infestation by A. fraterculus on the occurrence of bunch rot disease in the grape (cultivar ?Itália?) by evaluating grapes (a) punctured for oviposition by females of A. fraterculus, sterilized in laboratory with novaluron (40 mg L&#8722;1) and further spray-inoculated separately with Botrytis cinerea (1 × 106 conidia mL&#8722;1), Glomerella cingulata (1 × 106 conidia mL&#8722;1), and bacteria and yeast that cause sour rot (1 × 105 cells mL&#8722;1), (b) grapes punctured for oviposition by non-sterilized females with pathogen spraying, (c) grapes with mechanical wounds and pathogen spraying, (d) grapes with no wounds and with pathogen spraying, (e) grapes punctured for oviposition by A. fraterculus chemically sterilized in laboratory with novaluron, (f) grapes punctured for oviposition by A. fraterculus non-sterilized in laboratory with novaluron, (g) grapes with mechanical wounds, and (h) grapes with no sterilization or pathogen spraying. Our data indicated that the mechanical and oviposition wounds caused by A. fraterculus increased the percentage of grapes infected by B. cinerea, G. cingulata, and microorganisms of acid rot. The grape puncturing by A. fraterculus and the mechanical wound allows the penetration of B. cinerea and microorganisms leading to acid rot. We conclude that the fruit fly A. fraterculus may facilitate phytopathogens penetration leading to bunch rots in the table grape Itália.Disponível em:<http://link.springer.com/article/10.1007/s13744-016-0377-y

A multi-input UV-VIS airborne GASCOD/A4r spectroradiometer for the validation of satellite remote sensing measurements

The present paper describes a UV-VIS spectroradiometer named GASCOD/A4r developed at ISAC-CNR for remote sensing measurements aboard stratospheric M55-Geophysica aircraft, flying up to 21 km. Obtained experimental data are used for retrieving of NO2, O3 and of other minor gases atmospheric content, applying the DOAS (Differential Optical Absorption Spectroscopy) method. UV actinic flux and J(NO2) are also derived. All these parameters are used for satellite data validation tasks. The specific results obtained during dedicated aircraft missions in different geographical areas have already been utilized for ENVISAT validation