Robust tool condition monitoring in Ti6Al4V milling based on specific force coefficients and growing self-organizing maps

Tool condition monitoring (TCM) is a mean to optimize production systems trying to use cutting tool life at its best. Nevertheless, nowadays available TCM algorithms typically lack robustness in order to be consistently applied in industrial scenarios. In this paper, an unsupervised artificial intelligence technique, based on Growing Self-Organizing Maps (GSOM), is presented in synergy with real-time specific force coefficients (SFC) estimation through the regression of instantaneous cutting forces. The conceived approach allows robustly mapping the SFC, exploiting process parameters and similarity to manage the variability of their estimation due to unmodelled phenomena, like machine dynamics and tool run-out. The devised approach allowed detecting the tool end-of-life in cutting tests with variable lubrication, machine tool and cutting speed, through the adoption of a self-starting control chart running on real-time clustered data. The solution was validated through the comparison of the GSOM framework with respect to the optimized self-starting control chart applied without GSOM clustering. The GSOM reached a root mean squared percentage error (RMSPE) of 13.2% with respect to 56.1% obtained with the analogous control chart in a full-set optimization scenario. When optimised on tests for a unique machine tool and tested on another machine tool, GSOM scored an RMSPE of 34.5%, whereas the optimized control chart scored 64.5%

Energy Efficiency of the Vulcanization Process of a Bicycle Tyre

The production of tyres is one of the most energy consuming manufacturing activities in the rubber sector. In the production cycle of a tyre, the curing operation has the maximum energy loss. This is mostly due to the extensive use of steam as a source of heat and pressure in the vulcanization process. To the author’s knowledge, no scientific work is available in the literature where the energy efficiency of a tyre vulcanization press is estimated by means of a comprehensive model of all main components, including the moulds, the press with its heated plates, the bladder and, of course, the tyre. The present work aims at filling this gap. First, the press used for developing the model is described, along with its components and its typical product, a bicycle tyre. The instruments used for measuring flow rates, temperatures and pressures are also listed. Then, a numerical model is presented, that predicts the energy transfers occurring in the vulcanization press during a full process cycle. The numerical model, developed with the software Simcenter Amesim 2021.1, has been validated by means of measurements taken at the press. The results indicate that the amount of energy which is actually consumed by the tyre for its reticulation process amounts to less than 1% of the total energy expenditure. The paper demonstrates that the tyre industry is in urgent need of an electrification conversion of the traditional steam-based processes

The use of nematodes in assessing ecological conditions in shallow waters surrounding a Mediterranean harbour facility

The spatial distribution and structure of nematode assemblages in the area surrounding the harbour of Vado Ligure (Savona, NW Mediterranean) were studied in relation to the influence of natural and anthropogenic environmental factors. Stations were selected following an “anthropogenic gradient” from sites located near the city centre and its harbour to more pristine and distant sites. Sediment quality was determined by considering both sediment granulometric and chemical parameters (hydrocarbons, heavy metals, total organic matter, proteins, carbohydrates) as well as nematode abundance, diversity, life strategies, trophic structure and assemblage composition. A high correlation between environmental characteristics and the nematode response was found. On the basis of the comparison of these results, which identified three distinct sub-areas associated with different levels of environmental quality, a set of nematode indicator genera was selected for the future evaluation of quality status

Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Activation and Inhibition of Transglutaminase 2 in Mice

Transglutaminase 2 (TG2) is an allosterically regulated enzyme with transamidating, deamidating and cell signaling activities. It is thought to catalyze sequence-specific deamidation of dietary gluten peptides in the small intestines of celiac disease patients. Because this modification has profound consequences for disease pathogenesis, there is considerable interest in the design of small molecule TG2 inhibitors. Although many classes of TG2 inhibitors have been reported, thus far an animal model for screening them to identify promising celiac drug candidates has remained elusive. Using intraperitoneal administration of the toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly(I∶C)), we induced rapid TG2 activation in the mouse small intestine. Dose dependence was observed in the activation of TG2 as well as the associated villous atrophy, gross clinical response, and rise in serum concentration of the IL-15/IL-15R complex. TG2 activity was most pronounced in the upper small intestine. No evidence of TG2 activation was observed in the lung mucosa, nor were TLR7/8 ligands able to elicit an analogous response. Introduction of ERW1041E, a small molecule TG2 inhibitor, in this mouse model resulted in TG2 inhibition in the small intestine. TG2 inhibition had no effect on villous atrophy, suggesting that activation of this enzyme is a consequence, rather than a cause, of poly(I∶C) induced enteropathy. Consistent with this finding, administration of poly(I∶C) to TG2 knockout mice also induced villous atrophy. Our findings pave the way for pharmacological evaluation of small molecule TG2 inhibitors as drug candidates for celiac disease

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

ZMIZ1 Preferably Enhances the Transcriptional Activity of Androgen Receptor with Short Polyglutamine Tract

The androgen receptor (AR) is a ligand-induced transcription factor and contains the polyglutamine (polyQ) tracts within its N-terminal transactivation domain. The length of polyQ tracts has been suggested to alter AR transcriptional activity in prostate cancer along with other endocrine and neurologic disorders. Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably augments ARQ9 induced androgen-dependent transcription on three different androgen-inducible promoter/reporter vectors. A strong protein-protein interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9 was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR activity. Using the chromatin immunoprecipitation assays (ChIP), we further demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the prostate specific antigen (PSA) gene. These results demonstrate a novel regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate cancer cells