A transfer-learning approach to feature extraction from cancer transcriptomes with deep autoencoders

Publicado en Lecture Notes in Computer Science.The diagnosis and prognosis of cancer are among the more challenging tasks that oncology medicine deals with. With the main aim of fitting the more appropriate treatments, current personalized medicine focuses on using data from heterogeneous sources to estimate the evolu- tion of a given disease for the particular case of a certain patient. In recent years, next-generation sequencing data have boosted cancer prediction by supplying gene-expression information that has allowed diverse machine learning algorithms to supply valuable solutions to the problem of cancer subtype classification, which has surely contributed to better estimation of patient’s response to diverse treatments. However, the efficacy of these models is seriously affected by the existing imbalance between the high dimensionality of the gene expression feature sets and the number of sam- ples available for a particular cancer type. To counteract what is known as the curse of dimensionality, feature selection and extraction methods have been traditionally applied to reduce the number of input variables present in gene expression datasets. Although these techniques work by scaling down the input feature space, the prediction performance of tradi- tional machine learning pipelines using these feature reduction strategies remains moderate. In this work, we propose the use of the Pan-Cancer dataset to pre-train deep autoencoder architectures on a subset com- posed of thousands of gene expression samples of very diverse tumor types. The resulting architectures are subsequently fine-tuned on a col- lection of specific breast cancer samples. This transfer-learning approach aims at combining supervised and unsupervised deep learning models with traditional machine learning classification algorithms to tackle the problem of breast tumor intrinsic-subtype classification.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Therapeutic Radionuclides: Making the Right Choice

Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians

BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. METHODS: DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS: Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00–0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99–6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66–37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a significant association between rare S2 allele and HTG in Asian Indians

Single-Stage Repair versus Traditional Repair of High Anorectal Malformations, Functional Results’ Correlation with Kelly’s Score and Postoperative Magnetic Resonance Imaging Findings

Introduction: Posterior sagittal anorectoplasty (PSARP) is the standard treatment for anorectal malformations. In the present study, the clinical evaluation of anal continence was carried out using Kelly’s scoring system and the results of primary PSARP or abdomino-PSARP were compared with the traditional three-stage procedure and the functional outcome was correlated with the findings of MRI, which was used as an objective method of evaluation.Patients and methods: A total of 40 patients with intermediate and high anorectal malformations were studied and were divided into two groups on the basis of a random number table. The patients in group A were treated with a single-stage operation, whereas the patients in group B were treated with a standard staged operation (either PSARP or abdominoperineal pull-through). After clinical evaluation using the Kelly score, patients were divided into three clinical groups irrespective of whether they were operated in one stage or in three stages. All patients were subjected to MRI at the age of 3 years and the findings were correlated with the clinical scoring system.Result: Patients were categorized according to their Kelly’s scores as follows: group 1: clinically good (score 5–6); group 2: clinically fair (score 3–4); and group 3: clinically poor (score 0–2). The proportions of good development of the muscles (puborectalis, external sphincter muscle, and levator muscle hammock) were 78.9% in group 1, 40% in group 2, and none in group 3. Development of muscles was found to be a significant factor for anal continence. Other significant factors for anal continence are rectal diameter and anorectal angle.Conclusion: Clinical assessment using the Kelly score was similar for the single-stage operation and the staged procedure, and this was supported by MRI findings. Therefore, we recommend the single-stage procedure to achieve a better outcome in intermediate and high anorectal malformation.Keywords: Anorectal Malformations, MRI, Posterior Sagittal Anorectoplast

Research on information systems failures and successes: Status update and future directions

The final publication is available at Springer via http://dx.doi.org/10.1007/s10796-014-9500-yInformation systems success and failure are among the most prominent streams in IS research. Explanations of why some IS fulfill their expectations, whereas others fail, are complex and multi-factorial. Despite the efforts to understand the underlying factors, the IS failure rate remains stubbornly high. A Panel session was held at the IFIP Working Group 8.6 conference in Bangalore in 2013 which forms the subject of this Special Issue. Its aim was to reflect on the need for new perspectives and research directions, to provide insights and further guidance for managers on factors enabling IS success and avoiding IS failure. Several key issues emerged, such as the need to study problems from multiple perspectives, to move beyond narrow considerations of the IT artifact, and to venture into underexplored organizational contexts, such as the public sector. © 2014 Springer Science+Business Media New York

Condition Monitoring of Rotating Elements Using Acoustic Emission: Indian Scenario

The first experimental study in the world on the phenomenon of generation of Acoustic Emission dates back to the 1950’s when Josef Kaiser heard these emissions during metal failure. But unfortunately, the work could not get impetus because of the limited means of sensing high frequency waves and the lack of knowledge dissemination. In the 1970’s, the electronic instrumentation improved resulting in the increased activity centers of AE. At that time, Rao initiated work in this area at the Indian Institute of Science, Banglore for the first time in India. With the pioneering efforts of his group at IISc, new vistas were opened in this field. As a consequence of it, the first paper from India on this phenomenon was published in 1977 by Eshwar, et al. [1], The paper dealt with the study of the form of AE observed on the cracking/breaking of plywood with prepared defects

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Working Group Report: Heavy-Ion Physics and Quark-Gluon Plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of Quark-Gluon Plasma believed to have created in heavy-ion collisions and in early universe are reported.Comment: 20 pages, 6 eps figures, Heavy-ion physics and QGP activity report in "IX Workshop on High Energy Physics Phenomenology (WHEPP-09)" held in Institute of Physics, Bhubaneswar, India, during January 3-14, 2006. To be published in PRAMANA - Journal of Physics (Indian Academy of Science

Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions

Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons

Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the earliest stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age. It has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, we developed the fetal brain clock (FBC), a bespoke epigenetic clock trained in human prenatal brain samples in order to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons. The FBC was tested in two independent validation cohorts across a total of 194 samples, confirming that the FBC outperforms other established epigenetic clocks in fetal brain cohorts. We applied the FBC to DNA methylation data from iPSCs and embryonic stem cells and their derived neuronal precursor cells and neurons, finding that these cell types are epigenetically characterized as having an early fetal age. Furthermore, while differentiation from iPSCs to neurons significantly increases epigenetic age, iPSC-neurons are still predicted as being fetal. Together our findings reiterate the need to better understand the limitations of existing epigenetic clocks for answering biological research questions and highlight a limitation of iPSC-neurons as a cellular model of age-related diseases