Identification of the expressome by machine learning on omics data.

Accurate annotation of plant genomes remains complex due to the presence of many pseudogenes arising from whole-genome duplication-generated redundancy or the capture and movement of gene fragments by transposable elements. Machine learning on genome-wide epigenetic marks, informed by transcriptomic and proteomic training data, could be used to improve annotations through classification of all putative protein-coding genes as either constitutively silent or able to be expressed. Expressed genes were subclassified as able to express both mRNAs and proteins or only RNAs, and CG gene body methylation was associated only with the former subclass. More than 60,000 protein-coding genes have been annotated in the reference genome of maize inbred B73. About two-thirds of these genes are transcribed and are designated the filtered gene set (FGS). Classification of genes by our trained random forest algorithm was accurate and relied only on histone modifications or DNA methylation patterns within the gene body; promoter methylation was unimportant. Other inbred lines are known to transcribe significantly different sets of genes, indicating that the FGS is specific to B73. We accurately classified the sets of transcribed genes in additional inbred lines, arising from inbred-specific DNA methylation patterns. This approach highlights the potential of using chromatin information to improve annotations of functional genes

Industry 4.0 and sustainability: Towards conceptualization and theory

Both Industry 4.0 and sustainability have gained momentum in the academic, managerial and policy debate. Despite the relevance of the topics, the relation between Industry 4.0 and sustainability \u2013 revealed by many authors \u2013 is still unclear; literature is fragmented. This paper seeks to overcome this limit by developing a systematic literature review of 117 peer-reviewed journal articles. After descriptive and content analyses, the work presents a conceptualization and theoretical framework. The paper contributes to both theory and practice by advancing current understanding of Industry 4.0 and sustainability, especially the impact of Industry 4.0 technologies on sustainability practices and performance

Androgen deprivation and radiotherapy with or without docetaxel for localized high-risk prostate cancer: Long-term follow-up from the randomized NRG Oncology RTOG 0521 trial

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (\u3e50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel

Creation of helicopter dynamic systems digital twin using multibody simulations

International audienceThis paper presents a new approach to develop digital twins of helicopter dynamic systems. Helicopter industries attach growing attention to the development of digital twins to be more predictive of mechanical parts lifetime. The number of sensors available to measure loads during flights is limited. Complementary simulations are necessary to compute all the loads that the mechanical parts undergo. A new process is described to build these simulations fed with flights data records. Complexity of helicopters dynamics systems leads to create several local models of subsystems using a multibody dynamic formalism. A study focused on a swashplate rotor assembly is presented to illustrate this approach, including a new model of bearing and its validation based on bench tests

Algorithmic Price Discrimination and Consumer Protection. A Digital Arms Race?

none4siOnline market players are gradually gaining the capacity to adapt prices dynamically based on knowledge generated through vast amounts of data, so that, theoretically, every individual consumer can be charged the maximum price he or she is willing to pay. This has downsides for markets and society. European Union law insufficiently addresses these issues. Consumer-empowering technologies may help counter algortihmic price discruimination. We advocate for regulation to make the arms race between conumers and sellers more balanced by strengthening the digital tools available to consumer protection actors and to limit the battlefield by clarifying and refining the applica- ble rules and defining clearer categories of impermissible behaviours.openMateusz Grochowski; Agnieszka Jabłonowska; Francesca Lagioia; Giovanni SartorMateusz Grochowski; Agnieszka Jabłonowska; Francesca Lagioia; Giovanni Sarto

The future of manufacturing: A Delphi-based scenario analysis on Industry 4.0

Industry 4.0 is expected to impart profound changes to the configuration of manufacturing companies with regards to what their value proposition will be and how their production network, supplier base and customer interfaces will develop. The literature on the topic is still fragmented; the features of the emerging paradigm appear to be a contested territory among different academic disciplines. This study assumes a value chain perspective to analyze the evolutionary trajectories of manufacturing companies. We developed a Delphi-based scenario analysis involving 76 experts from academia and practice. The results highlight the most common expectations as well as controversial issues in terms of emerging business models, size, barriers to entry, vertical integration, rent distribution, and geographical location of activities. Eight scenarios provide a concise outlook on the range of possible futures. These scenarios are based on four main drivers which stem from the experts\u2019 comments: demand characteristics, transparency of data among value chain participants, maturity of additive manufacturing and advanced robotics, and penetration of smart products. Researchers can derive from our study a series of hypotheses and opportunities for future research on Industry 4.0. Managers and policymakers can leverage the scenarios in long-term strategic planning

Using supply chain databases in academic research: A methodological critique

This article outlines the main methodological implications of using Bloomberg SPLC, FactSet Supply Chain Relationships, and Mergent Supply Chain for academic purposes. These databases provide secondary data on buyer–supplier relationships that have been publicly disclosed. Despite the growing use of these databases in supply chain management (SCM) research, several potential validity and reliability issues have not been systematically and openly addressed. This article thus expounds on challenges of using these databases that are caused by (1) inconsistency between data, SCM constructs, and research questions (data fit); (2) errors caused by the databases' classifications and assumptions (data accuracy); and (3) limitations due to the inclusion of only publicly disclosed buyer–supplier relationships involving specific focal firms (data representativeness). The analysis is based on a review of previous studies using Bloomberg SPLC, FactSet Supply Chain Relationships, and Mergent Supply Chain, publicly available materials, interviews with information service providers, and the direct experience of the authors. Some solutions draw upon established methodological literature on the use of secondary data. The article concludes by providing summary guidelines and urging SCM researchers toward greater methodological transparency when using these databases

Advances in targeted Alpha therapy for prostate cancer

BACKGROUND: Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. DESIGN: In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. RESULTS: A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor (AR)-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. CONCLUSIONS: The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment

Exact Treatment of the Pauli Exclusion Operator in Nuclear Matter Calculation

Exact expressions of the Pauli exclusion operator Q in the nuclear matter calculation are presented in detail. Exact formulae are also given for the calculations of the single-particle-potential energy and the binding energy per nucleon with the exact Q operator. Numerical calculations of the G matrix in the lowest-order Brueckner theory are carried out to check the reliability of the standard angle-average approximation for the Q operator by employing the Bonn B and C NN potentials. It is observed that the exact treatment of the operator Q brings about non-negligible and attractive contributions to the binding energy.Comment: 16 pages, 3 figure