ROAD value-based detection for GAE enhanced interference mitigation in LDACS.

The increasing volume of air traffic has placed significant stress on the current Air Traffic Management (ATM) systems, especially concerning the use of Very High Frequency (VHF) communication bands. As air traffic continues to grow, the limitations of the existing spectrum and infrastructure necessitate significant upgrades to ensure safety, efficiency, and capacity. The modernization of air traffic management systems has led to the development and introduction of the L-band Digital Aeronautical Communication System (LDACS), a new communication protocol. LDACS is designed to operate alongside existing L-band systems, ensuring compatibility with legacy users. The coexistence of LDACS with legacy systems poses significant interference challenges, as any disruption in data retrieval can critically impact flight safety. This paper proposes four potential interference mitigation techniques that LDACS can employ to detect and reduce the primary source of interference: Distance Measuring Equipment (DME). The authors introduce a prototype LDACS receiver that uses Rank-Ordered Absolute Differences (ROAD) statistics for effective interference sensing and employs GAE-enhanced pulse peak processors to mitigate Distance Measuring Equipment (DME) interference. Unlike the current GAE-enhanced pulse peak processors, the proposed methods use ROAD value-based detection for identifying DME interference. The performance of the proposed methods - ROAD GAE enhanced Pulse Peak Attenuator (RGPPA), ROAD GAE enhanced Pulse Peak Limiter (RGPPL), ROAD joint GAE enhanced Pulse Peak Attenuator (RJGPPA), and ROAD joint GAE enhanced Pulse Peak Limiter (RJGPPL) is analyzed across different threshold ROAD values to determine their efficacy in various signal conditions. Moreover, the performance of the proposed methods is compared to existing methods such as conventional pulse blanking and GAE-enhanced nonlinear devices, which use the amplitude of the received signal for the detection of interference. Furthermore, the proposed method's performance is compared to another method, ROAD PB, which uses ROAD statistics to detect DME interference and pulse blanking for DME mitigation. The comparative results show that the proposed methods outperformed conventional pulse blanking and ROADPB. Besides, these methods outperformed existing GAE-enhanced methods for their optimum threshold ROAD value.

The Comparison of Newly Diagnosed Invasive Breast Patient Cohorts in Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC) and Other Real-World Databases.

BACKGROUND: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. OBJECTIVES: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases. METHODS: This study utilized GENIE-BPC, SEER, SEER-Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD-9/10-CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. RESULTS: Of female breast cancer patients in GENIE-BPC (n = 775), SEER (n = 548 336), SEER-Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE-BPC, compared to SEER/SEER-Medicare, had higher nuclear grades (%III-%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1-, 3-, and 5-year overall survival rates were lower in GENIE-BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER-Medicare (91.6%, 81.4%, 75.0%). CONCLUSION: Breast cancer patients in GENIE-BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE-BPC to the larger breast cancer population.

Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis.

BACKGROUND: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing-based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. METHODS: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. RESULTS: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type-specific mutation signature for chemotherapy selection. CONCLUSION: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Landscape and Saturation Analysis of Mutations Associated With Race in Cancer Genomes by Clinical Sequencing.

Differences in cancer genomes between racial groups may impact tumor biology and health disparities. However, the discovery of race-associated mutations is constrained by the limited representation and sample size of different racial groups in prior genomic studies. We evaluated the influence of race on the frequency of gene mutations using the Genomics, Evidence, Neoplasia, Information, Exchange database, a large genomic dataset aggregated from clinical sequencing. Matched cohort analyses were used to identify histology-specific race-associated mutations including increased TERT promoter mutations in Black and Asian patients with gliomas and bladder cancers, and a decreased frequency of mutations in DNA repair pathway genes and subunits of the SWI/SNF chromatin complex in Asian and Black patients across multiple cancer types. The distribution of actionable mutations in oncogenes was also race-specific, demonstrating how targeted therapies may have a disparate impact on racial groups. Down-sampling analyses indicate that larger sample sizes are likely to discover more race-associated mutations. These results provide a resource to understand differences in cancer genomes between racial groups which may inform the design of clinical studies and patient recruitment strategies in biomarker trials.

Prostate cancer genetic alterations in Hispanic men.

BACKGROUND: Differences in DNA alterations in prostate cancer among White, Black, and Asian men have been widely described. This is the first description of the frequency of DNA alterations in primary and metastatic prostate cancer samples of self-reported Hispanic men. METHODS: We utilized targeted next-generation sequencing tumor genomic profiles from prostate cancer tissues that underwent clinical sequencing at academic centers (GENIE 11th). We decided to restrict our analysis to the samples from Memorial Sloan Kettering Cancer Center as it was by far the main contributor of Hispanic samples. The numbers of men by self-reported ethnicity and racial categories were analyzed via Fisher's exact test between Hispanic-White versus non-Hispanic White. RESULTS AND LIMITATIONS: Our cohort consisted of 1412 primary and 818 metastatic adenocarcinomas. In primary adenocarcinomas, TMPRSS2 and ERG gene alterations were less common in non-Hispanic White men than Hispanic White (31.86% vs. 51.28%, p = 0.0007, odds ratio [OR] = 0.44 [0.27-0.72] and 25.34% vs. 42.31%, p = 0.002, OR = 0.46 [0.28-0.76]). In metastatic tumors, KRAS and CCNE1 alterations were less prevalent in non-Hispanic White men (1.03% vs. 7.50%, p = 0.014, OR = 0.13 [0.03, 0.78] and 1.29% vs. 10.00%, p = 0.003, OR = 0.12 [0.03, 0.54]). No significant differences were found in actionable alterations and androgen receptor mutations between the groups. Due to the lack of clinical characteristics and genetic ancestry in this dataset, correlation with these could not be explored. CONCLUSION: DNA alteration frequencies in primary and metastatic prostate cancer tumors differ among Hispanic-White and non-Hispanic White men. Notably, we found no significant differences in the prevalence of actionable genetic alterations between the groups, suggesting that a significant number of Hispanic men could benefit from the development of targeted therapies.

Molecular profiling of colorectal cancer in a genetically admixed Hispanic population.

BACKGORUND: Colorectal cancer (CRC) is among the leading causes of cancer-related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. METHODS: We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next-generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan-Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)-Non-Hispanic, and GENIE-Hispanic datasets. RESULTS: Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE-Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability-high (MSI), wild-type KRAS, wild-type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. CONCLUSION: This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non-Hispanic and USH populations.

Validation of a high-confidence regulatory network for gene-to-NUE phenotype in field-grown rice.

Nitrogen (N) and Water (W) - two resources critical for crop productivity - are becoming increasingly limited in soils globally. To address this issue, we aim to uncover the gene regulatory networks (GRNs) that regulate nitrogen use efficiency (NUE) - as a function of water availability - in Oryza sativa, a staple for 3.5 billion people. In this study, we infer and validate GRNs that correlate with rice NUE phenotypes affected by N-by-W availability in the field. We did this by exploiting RNA-seq and crop phenotype data from 19 rice varieties grown in a 2x2 N-by-W matrix in the field. First, to identify gene-to-NUE field phenotypes, we analyzed these datasets using weighted gene co-expression network analysis (WGCNA). This identified two network modules ("skyblue" & "grey60") highly correlated with NUE grain yield (NUEg). Next, we focused on 90 TFs contained in these two NUEg modules and predicted their genome-wide targets using the N-and/or-W response datasets using a random forest network inference approach (GENIE3). Next, to validate the GENIE3 TF→target gene predictions, we performed Precision/Recall Analysis (AUPR) using nine datasets for three TFs validated in planta. This analysis sets a precision threshold of 0.31, used to "prune" the GENIE3 network for high-confidence TF→target gene edges, comprising 88 TFs and 5,716 N-and/or-W response genes. Next, we ranked these 88 TFs based on their significant influence on NUEg target genes responsive to N and/or W signaling. This resulted in a list of 18 prioritized TFs that regulate 551 NUEg target genes responsive to N and/or W signals. We validated the direct regulated targets of two of these candidate NUEg TFs in a plant cell-based TF assay called TARGET, for which we also had in planta data for comparison. Gene ontology analysis revealed that 6/18 NUEg TFs - OsbZIP23 (LOC_Os02g52780), Oshox22 (LOC_Os04g45810), LOB39 (LOC_Os03g41330), Oshox13 (LOC_Os03g08960), LOC_Os11g38870, and LOC_Os06g14670 - regulate genes annotated for N and/or W signaling. Our results show that OsbZIP23 and Oshox22, known regulators of drought tolerance, also coordinate W-responses with NUEg. This validated network can aid in developing/breeding rice with improved yield on marginal, low N-input, drought-prone soils.

A Pan-Cancer Assessment of RB1/TP53 Co-Mutations.

Nearly all tumors have multiple mutations in cancer-causing genes. Which of these mutations act in tandem with other mutations to drive malignancy and also provide therapeutic vulnerability? To address this fundamental question, we conducted a pan-cancer screen of co-mutation enrichment (looking for two genes mutated together in the same tumor at a statistically significant rate) using the AACR-GENIE 11.0 data (AACR, Philadelphia, PA, USA). We developed a web tool for users to review results and perform ad hoc analyses. From our screen, we identified a number of such co-mutations and their associated lineages. Here, we focus on the RB1/TP53 co-mutation, which we discovered was the most frequently observed co-mutation across diverse cancer types, with particular enrichment in small cell carcinomas, neuroendocrine carcinomas, and sarcomas. Furthermore, in many cancers with a substantial fraction of co-mutant tumors, the presence of concurrent RB1/TP53 mutations is associated with poor clinical outcomes. From pan-cancer cell line multi-omics and functional screening datasets, we identified many targetable co-mutant-specific molecular alterations. Overall, our analyses revealed the prevalence, cancer type-specificity, clinical significance, and therapeutic vulnerabilities of the RB1/TP53 co-mutation in the pan-cancer landscape and provide a roadmap forward for future clinical translational research.

Evaluating the performance of random forest and iterative random forest based methods when applied to gene expression data.

Gene-to-gene networks, such as Gene Regulatory Networks (GRN) and Predictive Expression Networks (PEN) capture relationships between genes and are beneficial for use in downstream biological analyses. There exists multiple network inference tools to produce these gene-to-gene networks from matrices of gene expression data. Random Forest-Leave One Out Prediction (RF-LOOP) is a method that has been shown to be efficient at producing these gene-to-gene networks, frequently known as GEne Network Inference with Ensemble of trees (GENIE3). Random Forest can be replaced in this process by iterative Random Forest (iRF), which performs variable selection and boosting. Here we validate that iterative Random Forest-Leave One Out Prediction (iRF-LOOP) produces higher quality networks than GENIE3 (RF-LOOP). We use both synthetic and empirical networks from the Dialogue for Reverse Engineering Assessment and Methods (DREAM) Challenges by Sage Bionetworks, as well as two additional empirical networks created from Arabidopsis thaliana and Populus trichocarpa expression data.

A Deep Learning-Based Chinese Semantic Parser for the Almond Virtual Assistant.

Almond is an extendible open-source virtual assistant designed to help people access Internet services and IoT (Internet of Things) devices. Both are referred to as skills here. Service providers can easily enable their devices for Almond by defining proper APIs (Application Programming Interfaces) for ThingTalk in Thingpedia. ThingTalk is a virtual assistant programming language, and Thingpedia is an application encyclopedia. Almond uses a large neural network to translate user commands in natural language into ThingTalk programs. To obtain enough data for the training of the neural network, Genie was developed to synthesize pairs of user commands and corresponding ThingTalk programs based on a natural language template approach. In this work, we extended Genie to support Chinese. For 107 devices and 261 functions registered in Thingpedia, 649 Chinese primitive templates and 292 Chinese construct templates were analyzed and developed. Two models, seq2seq (sequence-to-sequence) and MQAN (multiple question answer network), were trained to translate user commands in Chinese into ThingTalk programs. Both models were evaluated, and the experiment results showed that MQAN outperformed seq2seq. The exact match, BLEU, and F1 token accuracy of MQAN were 0.7, 0.82, and 0.88, respectively. As a result, users could use Chinese in Almond to access Internet services and IoT devices registered in Thingpedia.

Computational methods and translational applications for targeted next-generation sequencing platforms.

During the past decade, next-generation sequencing (NGS) technologies have become widely adopted in cancer research and clinical care. Common applications within the clinical setting include patient stratification into relevant molecular subtypes, identification of biomarkers of response and resistance to targeted and systemic therapies, assessment of heritable cancer risk based on known pathogenic variants, and longitudinal monitoring of treatment response. The need for efficient downstream processing and reliable interpretation of sequencing data has led to the development of novel algorithms and computational pipelines, as well as structured knowledge bases that link genomic alterations to currently available drugs and ongoing clinical trials. Cancer centers around the world use different types of targeted solid-tissue and blood based NGS assays to analyze the genomic and transcriptomic profile of patients as part of their routine clinical care. Recently, cross-institutional collaborations have led to the creation of large pooled datasets that can offer valuable insights into the genomics of rare cancers.

Advancing undergraduate synthetic biology education: insights from a Canadian iGEM student perspective.

The last two decades have seen vigorous activity in synthetic biology research and the ever-increasing applications of these technologies. However, pedagogical research pertaining to teaching synthetic biology is scarce, especially when compared to other science and engineering disciplines. Within Canada, there are only three universities that offer synthetic biology programs, two of which are at the undergraduate level. Rather than taking place in formal academic settings, many Canadian undergraduate students are introduced to synthetic biology through participation in the annual International Genetically Engineered Machine (iGEM) competition. Although the iGEM competition has had a transformative impact on synthetic biology training in other nations, its impact in Canada has been relatively modest. Consequently, the iGEM competition remains a major setting for synthetic biology education in Canada. To promote further development of synthetic biology education, we surveyed undergraduate students from the Canadian iGEM design teams of 2019. We extracted insights from these data using qualitative analysis to provide recommendations for best teaching practices in synthetic biology undergraduate education, which we describe through our proposed Framework for Transdisciplinary Synthetic Biology Education (FTSBE).

O místico: intuição, verdade e beleza / The mystic: intuition, truth and beauty / El místico: intuición, verdad y belleza / Le mystique: intuition, vérité et beauté

A autora examina o controverso relacionamento entre o conceito O de Bion e o misticismo. Acesso a O representa essencialmente um profundo nível de intuição que abarca tanto o território do sonhar quanto o do pensar, uma espécie de "sonho acordado". Controvérsias em torno dessas ideias refletem a crença de alguns analistas de que o misticismo é antitético à ciência, apesar de Bion afirmar claramente que "os Místicos aparecem em qualquer religião, ciência, tempo ou lugar". A autora faz uma clara distinção entre o significado religioso de "místico" e o do ponto de vista psicanalítico de Bion do místico, uma distinção evidente no seu uso do termo "místico" como sinônimo de "gênio" ou "pessoa excepcional". Tanto nas artes quanto nas ciências, essa intuições são estados de mente cultivados por disciplina, trabalho árduo e paixão pela verdade. Exemplos clínicos ilustram essas ideias.

The author examines the controversial relationship between Bion's concept of O and mysticism. Access to O essentially represents a profound level of intuition that straddles the realms of dreaming and thinking, a kind of "waking dream". Controversies surrounding these ideas reflect some analysts' belief that mysticism is antithetical to science, although as Bion clearly states, "Mystics appear in any religion, science, time, or place." The author distinguishes between the religious meaning of "mystic" and Bion's psychoanalytic view of the mystic, a distinction evident in his use of the term "mystic" as synonymous with 'genius" or "exceptional person." Whether in the Arts or Sciences, these intuitions are states of mind cultivated through discipline, hard work, and a passion for truth. Clinical examples illustrate these ideas.

La autora examina la polémica relación entre el concepto O de Bion y el misticismo. Acceso a O representa esencialmente un profundo nivel de intuición que abarca tanto el territorio del soñar como el del pensar, una especie de "sueño despierto". Controversias alrededor de esas ideas reflejan la creencia de algunos analistas de que el misticismo es una antítesis a la ciencia, a pesar de Bion afirmar claramente que "los Místicos aparecen en cualquier religión, ciencia, tiempo, o lugar". La autora distingue entre el significado religioso de "místico" y desde el punto de vista psicoanalítico de Bion de místico, una distinción evidente en su uso del término "místico" como sinónimo de "genio" o "persona excepcional". Tanto en las artes como en las ciencias, esas intuiciones son estados de mente cultivados a través de la disciplina, del trabajo duro, y de la pasión por la verdad. Ejemplos clínicos demuestran esas ideas.

L'auteure examine le rapport controversé entre le concept O de Bion et le mysticisme. L'accès à O représente essentiellement un niveau profond d'intuition qui renferme autant la compétence de rêver que celle de penser - un genre de « rêve éveillé ¼. La croyance de certains analystes qui considèrent que le mysticisme est antithétique à la science, met en évidence des controverses autour de ces idées, bien que Bion ait clairement affirmé que « les Mystiques apparaissent en tout(e) religion, science, temps ou lieux ¼. L'auteure fait une distinction claire entre le sens religieux de « mystique ¼ et le « mystique ¼ en tant que synonyme de « génie ¼ ou de « personne exceptionnelle ¼. Aussi bien chez les arts que chez les sciences, ces intuitions sont des états d'esprit cultivés par l'intermédiaire de la discipline, du travail ardu, et de la passion pour la vérité. Les idées présentées sont illustrées par des exemples cliniques.

[Pharmaceutical biotechnologies: drawing out the genome to develop, improve and personalize therapies and patient care]. / L'évolution des biotechnologies pharmaceutiques : faire parler le génome pour développer, améliorer et personnaliser les thérapies et la prise en charge des patients.

Thanks to high-throughput sequencing with technologies, which allow the reading of more than 100 million bases in one day with reduced cost, our knowledge about prokaryotic, eukaryotic and viral genomes has significantly increased since the 2000s. The multiplication of genetic engineering tools including DNA polymerases, restriction enzymes and genome editing enzymes and the development of other "omic" technologies such as transcriptomics, proteomics, and metabolomics, have allowed pharmaceutical biotechnologies to favor the identification and validation of various diagnostic and therapeutic targets underlying the development of targeted therapies. Indeed, these advances have supported a better understanding of pathologies as well as an improvement in their diagnosis, through the identification of biomarkers, considerably favoring more personalized and more efficient patients' care. The orientation towards more targeted treatments was initiated by the development of recombinant proteins, and more recently monoclonal antibodies, which can block protein functions and/or modulate immune responses. Gene therapy is also promising, by inserting a gene into patients' cells to overcome rare diseases and autologous or heterologous cell-based therapies are also under development. Although their history is recent, pharmaceutical biotechnologies are evolving rapidly and offer exciting prospects at the dawn of precision medicine.

TITLE: L'évolution des biotechnologies pharmaceutiques : faire parler le génome pour développer, améliorer et personnaliser les thérapies et la prise en charge des patients. ABSTRACT: Grâce à l'accroissement des connaissances associées aux génomes permis par le séquençage à haut débit, à la multiplication des outils d'ingénierie génétique ainsi qu'aux autres technologies « omiques ¼, les biotechnologies pharmaceutiques ont favorisé l'identification et la validation de nombreuses cibles diagnostiques et thérapeutiques et ont ainsi conduit au développement de nombreuses thérapies ciblées. Bien que leur histoire soit récente, les biotechnologies pharmaceutiques évoluent rapidement et offrent des perspectives réjouissantes à l'aube de la médecine de précision.

[Ecological engineering, a science by and for the living]. / Le Génie Écologique, une science par et pour le vivant.

In the 1960s, the concept of ecological engineering was theorized by Howard Odum, who showed the possibility of controlling the evolutionary trajectories of ecosystems by influencing their natural dynamics. H. Odum gave the definition of ecological engineering as "human manipulation of the environment using small amounts of additional energy to control systems in which the main sources of energy still come from natural sources". Since then, this definition has evolved, and several are currently used. The discipline then diversified, currently counting no less than 15 different fields of application, notably landscape architecture, phytoremediation, urban planning, agro-engineering, etc. Bibliometry concerning ecological engineering clearly shows the importance of this discipline worldwide. We notice its continuous evolution since 1995 with an almost exponential increase of the number of publications each year, with more than 6,500 publications in total coming from all continents.

TITLE: Le Génie Écologique, une science par et pour le vivant. ABSTRACT: Dans les années 1960, le concept de génie écologique a été théorisé par Howard Odum, qui a montré la possibilité de contrôler les trajectoires évolutives des écosystèmes en influant sur leurs dynamiques naturelles. Depuis, les définitions de ce concept ont évolué et la discipline s'est diversifiée, comptant actuellement pas moins de 15 domaines d'applications différents. La bibliométrie concernant l'ingénierie écologique montre bien l'importance de cette discipline à travers le monde. On remarque son évolution continuelle depuis les années 1995 avec une augmentation quasi exponentielle du nombre de publications chaque année, avec plus de 6500 publications au total provenant de tous les continents.

Solilóquios com um fósforo queimado: notas do cafezinho / Soliloquies with a burnt matchstick: notes from the coffee break / Soliloquios con un partido quemado: notas de café / Soliloques avec une allumette brûlée: notes de café

As intuições originais de Freud se verticalizaram em aprofundamentos teórico-clínicos e se horizontalizaram tornando-se populares. Em ambos os sentidos, o movimento trouxe novos desafios para a comunicação, tanto em sentido alongado, com o grande público, como em sentido lateral, de diálogo entre pares. Apreensões que privilegiam disjunções, e não cesuras entre novos desenvolvimentos epistemológicos e teorias consagradas, podem contribuir para um sentimento de expansão dispersiva do universo de discurso em psicanálise. Por fim, analisa-se o desafio que representa a vulgarização de formulações geniais, passíveis de um processo de kitschização epistemológica, com subtração de seus aspectos subversivos.

Freud's original intuitions became vertical in theoretical-clinical depths and horizontalized becoming popular. In both directions, the movement brought new challenges for communication, both in an elongated sense, with the general public, and in a lateral sense, of dialogue between peers. Apprehensions that privilege disjunctions, and not caesuras between new epistemological developments and established theories can contribute to a feeling of dispersive expansion of the universe of discourse in psychoanalysis. Finally, we analyze the challenge that represents the vulgarization of brilliant formulations, subject to a process of epistemological kitschization and subtraction of its subversive aspects.

Las intuiciones originales de Freud se volvieron verticales en profundidades teórico-clínicas y se horizontalizaron volviéndose populares. En ambas direcciones, el movimiento trajo nuevos retos para la comunicación, tanto en sentido alargado, con el público en general, como en sentido lateral, de diálogo entre pares. Las aprehensiones que privilegian las disyunciones y las no vacilaciones entre los nuevos desarrollos epistemológicos y las teorías establecidas pueden contribuir a un sentimiento de expansión dispersiva del universo del discurso en psicoanálisis. Finalmente, analizamos el desafío que representa la vulgarización de formulaciones brillantes, sometidas a un proceso de kitschización epistemológica y sustracción de sus aspectos subversivos.

Les intuitions originales de Freud sont devenues verticales dans les profondeurs théorico-cliniques et horizontalisées devenant populaires. Dans les deux sens, le mouvement a apporté de nouveaux défis de communication, à la fois dans un sens allongé, avec le grand public, et dans un sens latéral, de dialogue entre pairs. Les appréhensions qui privilégient les disjonctions, et non les césures entre les nouveaux développements épistémologiques et les théories établies peuvent contribuer à un sentiment d'expansion dispersive de l'univers du discours en psychanalyse. Enfin, nous analysons le défi que représente la vulgarisation de formulations brillantes, soumises à un processus de kitschisation épistémologique et de soustraction de ses aspects subversifs.

Utility of Extrapolating Human S1500+ Genes to the Whole Transcriptome: Tunicamycin Case Study.

The TempO-Seq S1500+ platform(s), now available for human, mouse, rat, and zebrafish, measures a discrete number of genes that are representative of biological and pathway co-regulation across the entire genome in a given species. While measurement of these genes alone provides a direct assessment of gene expression activity, extrapolating expression values to the whole transcriptome (~26 000 genes in humans) can estimate measurements of non-measured genes of interest and increases the power of pathway analysis algorithms by using a larger background gene expression space. Here, we use data from primary hepatocytes of 54 donors that were treated with the endoplasmic reticulum (ER) stress inducer tunicamycin and then measured on the human S1500+ platform containing ~3000 representative genes. Measurements for the S1500+ genes were then used to extrapolate expression values for the remaining human transcriptome. As a case study of the improved downstream analysis achieved by extrapolation, the "measured only" and "whole transcriptome" (measured + extrapolated) gene sets were compared. Extrapolation increased the number of significant genes by 49%, bringing to the forefront many that are known to be associated with tunicamycin exposure. The extrapolation procedure also correctly identified established tunicamycin-related functional pathways reflected by coordinated changes in interrelated genes while maintaining the sample variability observed from the "measured only" genes. Extrapolation improved the gene- and pathway-level biological interpretations for a variety of downstream applications, including differential expression analysis, gene set enrichment pathway analysis, DAVID keyword analysis, Ingenuity Pathway Analysis, and NextBio correlated compound analysis. The extrapolated data highlight the role of metabolism/metabolic pathways, the ER, immune response, and the unfolded protein response, each of which are key activities associated with tunicamycin exposure that were unrepresented or underrepresented in one or more of the analyses of the original "measured only" dataset. Furthermore, the inclusion of the extrapolated genes raised "tunicamycin" from third to first upstream regulator in Ingenuity Pathway Analysis and from sixth to second most correlated compound in NextBio analysis. Therefore, our case study suggests an approach to extend and enhance data from the S1500+ platform for improved insight into biological mechanisms and functional outcomes of diseases, drugs, and other perturbations.