Process Mining for Dynamic Modeling of Smart Manufacturing Systems: Data Requirements

Modern manufacturing systems can benefit from the use of digital tools to support both short- and long-term decisions. Meanwhile, such systems reached a high level of complexity and are frequently subject to modifications that can quickly make the digital tools obsolete. In this context, the ability to dynamically generate models of production systems is essential to guarantee their exploitation on the shop-floors as decision-support systems. The literature offers approaches for generating digital models based on real-time data streams. These models can represent a system more precisely at any point in time, as they are continuously updated based on the data. However, most approaches consider only isolated aspects of systems (e.g., reliability models) and focus on a specific modeling purpose (e.g., material flow identification). The research challenge is therefore to develop a novel framework that systematically enables the combination of models extracted through different process mining algorithms. To tackle this challenge, it is critical to define the requirements that enable the emergence of automated modeling and simulation tasks. In this paper, we therefore derive and define data requirements for the models that need to be extracted. We include aspects such as the structure of the manufacturing system and the behavior of its machines. The paper aims at guiding practitioners in designing coherent data structures to enable the coupling of model generation techniques within the digital support system of manufacturing companies

Genetic diversity of the genus Prunus based on per se evaluation of peach clonal rootstocks.

A aplicação de análises multivariadas e quantificação da divergência genética fornecem parâmetros que favorecem a seleção de porta-enxertos superiores. O objetivo deste trabalho foi avaliar a viabilidade técnica do uso de parte da diversidade genética do gênero Prunus como porta-enxerto clonal do pessegueiro ?BRS-Libra?. O pomar experimental faz parte de uma rede nacional de avaliação de porta-enxertos para prunáceas, sob a coordenação geral da Embrapa Clima Temperado. O delineamento experimental foi em blocos ao acaso e a coleta de dados ocorreu no ciclo produtivo 2016/2017. Foram realizadas análises físicas (área de secção do tronco, massa média de frutos) e química (sólidos solúveis), além da quantificação da produtividade estimada das plantas. Os dados obtidos foram submetidos ao teste de normalidade de Shapiro-Wilk, ao nível 5% de probabilidade, sendo posteriormente realizado o agrupamento dos porta-enxertos através do método hierárquico UPGMA. A realização do agrupamento resultou na formação de cinco grupos. As cultivares do grupo I, Mirabolano 29C e Marianna 2624, apresentaram incompatibilidade de enxertia com a cultivar BRS-Libra. Semelhantemente, as cultivares do grupo II apresentaram sintomas característicos de incompatibilidade de enxertia, resultando em pouco desenvolvimento. Os grupos III e IV são compostos por cultivares que apresentaram baixo e médio vigor, com boas perspectivas de uso para formar pomares em alta densidade, enquanto as cultivares do grupo V destacaram-se por apresentar alto vigor, recomendadas para pomares de baixa densidade. O uso de diferentes porta-enxertos influencia no comportamento da cultivar BRS-Libra no vigor e produção de frutos, havendo divergência genética entre eles

Neuroprotective role of phosphoserine in primary open-angle glaucoma patients

OBJECTIVE: To evaluate the neuroprotective role of phosphoserine (P-Ser) in primary open-angle glaucoma (POAG) patients and to compare its therapeutic effectiveness to placebo treatment. PATIENTS AND METHODS: Fifty-one patients (24 males and 27 females) between 35 and 61 years (average 46 years ± 3.8 SD) affected by POAG were enrolled in this study. Patients were divided in two groups: group A included 28 subjects that received an oral P-Ser treatment for 12 months; and group B included 23 subjects that received an oral placebo treatment for 12 months. Complete ophthalmological examination, standard automated perimetric examination, analysis of ON fibers via scanning laser polarimetry and glaucoma staging was performed in all patients at enrolment and 1, 3, 6, and 12 months after. Statistical analysis was performed using STATA 14.0 (Collage Station, TX, USA). RESULTS: Mean deviation (MD) and pattern standard deviation (PSD) analysis by means of 30-2 full threshold of the visual fields (VFs), retinal nerve fiber layer (RNFL) thickness by means of GDx, and IOP were considered to evaluate P-Ser therapy effectiveness in both groups. A statistically significant improvement (p<0.05) in VF, RNFL thickness and IOP compared to pre-treatment was found in patients in group A. CONCLUSIONS: Our study shows a significant improvement in several variables in patients with glaucoma treated with P-Ser compared to placebo and suggests a potential neuroprotective effect of P-Ser in treating glaucoma patients in association with the traditional hypotonic topical therapy

Patient adherence to and tolerability of self-administered interferon β-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study

<p>Abstract</p> <p>Background</p> <p>Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS).</p> <p>Methods</p> <p>BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device.</p> <p>Results</p> <p>Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (<it>P </it>= 0.821) or PASAT (<it>P </it>= 0.952) scores, or pre-study therapy (<it>P </it>= 0.303). No significant changes (baseline-Week 12) in mean HADS depression (<it>P </it>= 0.482) or anxiety (<it>P </it>= 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated. Mean MSTCQ scores for 'flu-like' symptoms (<it>P </it>= 0.022) and global side effects (<it>P </it>= 0.002) significantly improved from Week 4-12. Mean MSTCQ scores for pain at injection site and injection pain increased from Week 4-12 (<it>P </it>< 0.001). Adverse events were mild/moderate. No new safety signals were identified.</p> <p>Conclusion</p> <p>Convenience and ease of use of the autoinjection device may improve adherence and, therefore, outcomes, in patients with RRMS receiving sc IFN β-1a.</p> <p>Trial registration</p> <p>EU Clinical Trials Register (EU-CTR; <url>http://www.clinicaltrialsregister.eu</url>): 2009-013333-24</p

An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects

<p>Abstract</p> <p>Background</p> <p>The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients.</p> <p>Methods</p> <p>This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout.</p> <p>Results</p> <p>Seventy-one (96%) patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3) on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy). Ninety-four percent of patients preferred the prefilled pen over the prefilled syringe. Induction of serum neopterin levels, serving as a biomarker for type 1 interferon action, was similar to that of the prefilled syringe. The prefilled pen demonstrated a safety profile comparable to the prefilled syringe.</p> <p>Conclusions</p> <p>The prefilled pen is a safe and effective device for administration of IM IFNβ-1a and represents an alternative method for self-injection for MS patients using this therapy.</p> <p>Trial registration</p> <p>This study is registered at clinicaltrials.gov, identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00828204">NCT00828204</a></p

INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P 64 10-3 . Nine genes with a P 64 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS &amp; INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia

Observation of the Shadowing of Cosmic Rays by the Moon using a Deep Underground Detector

Using data collected by the MACRO experiment during the years 1989-1996, we show evidence for the shadow of the moon in the underground cosmic ray flux with a significance of 3.6 sigma. This detection of the shadowing effect is the first by an underground detector. A maximum-likelihood analysis is used to determine that the angular resolution of the apparatus is 0.9+/-0.3 degrees. These results demonstrate MACRO's capabilities as a muon telescope by confirming its absolute pointing ability and quantifying its angular resolution.Comment: 14 pages, 8 figures Submitted to Phys. Rev.

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199