A new energy saving load adaptive counterbalance valve

The paper shows standard circuits with load reactive and non load reactive counterbalance valves. A Matlab simulation based on a linear model for the circuit with load reactive counterbalance valves shows what parameters have a significant influence on the stability of the system. The most important parameters of the counterbalance valve that influence the stability are pilot gain and relief gain. The factors describe how pilot pressure and load pressure affect the flow across the counterbalance valve. A new counterbalance valve (patent pending) has the pilot gain and relief gain required for stability only in operating ranges that require the parameters for stability. When the load is not moving or the counterbalance valve is not required for positive (non overrunning) loads, the new valve has a higher pilot ratio, which means that the valve opens further at lower inlet pressures. The new counterbalance valves saves about 30% power compared with a standard counterbalance valve that has the same parameters for stability when it is lowering an overrunning load. The standard counterbalance can be replaced with the new load adaptive valve in the same cavity. The paper shows test results and the design of the valve

Framework for holistic online optimization of milling machine conditions to enhance machine efficiency and sustainability

This study addresses the challenge of the optimization of milling in industrial production, focusing on developing and applying a novel framework for optimising manufacturing processes. Recognising a gap in current methods, the research primarily targets the underutilisation of advanced data analysis and machine learning techniques in industrial settings. The proposed framework integrates these technologies to refine machining parameters more effectively than conventional approaches. The research method involved the development of the framework for the realisation and analysis of measurement data from milling machines, focusing on six machine parts and employing a machine learning system for optimization and evaluation. The developed and realised framework in the form of a software demonstrator showed its applicability in different experiments. This research enables easy deployment of data-driven techniques for sustainable industrial practices, highlighting the potential of this framework for transforming manufacturing processes.Ministry of Science, Research and Arts of the Federal State of Baden-Württember

Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages

Oxygen is a critical parameter proposed to modulate the functions of chondrocytes ex-vivo as well as in damaged joints. This article investigates the effect of low (more physiological) oxygen percentage on the biosynthetic and catabolic activity of human articular chondrocytes (HAC) at different phases of in vitro culture

Historical Newspaper Content Mining: Revisiting the impresso Project's Challenges in Text and Image Processing, Design and Historical Scholarship

impresso. Media Monitoring of the Past is an interdisciplinary research project in which a team of computational linguists, designers and historians collaborate on the datafication of a multilingual corpus of digitised historical newspapers. The primary goals of the project are to improve text mining tools for historical text, to enrich historical newspapers with (semi-) automatically generated data and to integrate such data into historical research workflows by means of a newly developed user interface. In this paper we discuss our efforts to overcome inherent challenges and to integrate text mining and data visualisation applications in general historical research practices which are characterised by search operations as well as the need to create topical collections

Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury.

Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. Accordingly, there is a need for more predictive tools to assess hepatotoxicity risk in drug discovery. Three-dimensional (3D) spheroid hepatic cultures have emerged as promising tools to assess mechanisms of hepatotoxicity, as they demonstrate enhanced liver phenotype, metabolic activity, and stability in culture not attainable with conventional two-dimensional hepatic models. Increased sensitivity of these models to drug-induced cytotoxicity has been demonstrated with relatively small panels of hepatotoxicants. However, a comprehensive evaluation of these models is lacking. Here, the predictive value of 3D human liver microtissues (hLiMT) to identify known hepatotoxicants using a panel of 110 drugs with and without clinical DILI has been assessed in comparison to plated two-dimensional primary human hepatocytes (PHH). Compounds were treated long-term (14 days) in hLiMT and acutely (2 days) in PHH to assess drug-induced cytotoxicity over an 8-point concentration range to generate IC50 values. Regardless of comparing IC50 values or exposure-corrected margin of safety values, hLiMT demonstrated increased sensitivity in identifying known hepatotoxicants than PHH, while specificity was consistent across both assays. In addition, hLiMT out performed PHH in correctly classifying hepatotoxicants from different pharmacological classes of molecules. The hLiMT demonstrated sufficient capability to warrant exploratory liver injury biomarker investigation (miR-122, HMGB1, α-GST) in the cell-culture media. Taken together, this study represents the most comprehensive evaluation of 3D spheroid hepatic cultures up to now and supports their utility for hepatotoxicity risk assessment in drug discovery

Pulmonary cancers across different histotypes share hybrid tuft cell/ionocyte-like molecular features and potentially druggable vulnerabilities

Tuft cells are chemosensory epithelial cells in the respiratory tract and several other organs. Recent studies revealed tuft cell-like gene expression signatures in some pulmonary adenocarcinomas, squamous cell carcinomas (SQCC), small cell carcinomas (SCLC), and large cell neuroendocrine carcinomas (LCNEC). Identification of their similarities could inform shared druggable vulnerabilities. Clinicopathological features of tuft cell-like (tcl) subsets in various lung cancer histotypes were studied in two independent tumor cohorts using immunohistochemistry (n = 674 and 70). Findings were confirmed, and additional characteristics were explored using public datasets (RNA seq and immunohistochemical data) (n = 555). Drug susceptibilities of tuft cell-like SCLC cell lines were also investigated. By immunohistochemistry, 10–20% of SCLC and LCNEC, and approximately 2% of SQCC expressed POU2F3, the master regulator of tuft cells. These tuft cell-like tumors exhibited “lineage ambiguity” as they co-expressed NCAM1, a marker for neuroendocrine differentiation, and KRT5, a marker for squamous differentiation. In addition, tuft cell-like tumors co-expressed BCL2 and KIT, and tuft cell-like SCLC and LCNEC, but not SQCC, also highly expressed MYC. Data from public datasets confirmed these features and revealed that tuft cell-like SCLC and LCNEC co-clustered on hierarchical clustering. Furthermore, only tuft cell-like subsets among pulmonary cancers significantly expressed FOXI1, the master regulator of ionocytes, suggesting their bidirectional but immature differentiation status. Clinically, tuft cell-like SCLC and LCNEC had a similar prognosis. Experimentally, tuft cell-like SCLC cell lines were susceptible to PARP and BCL2 co-inhibition, indicating synergistic effects. Taken together, pulmonary tuft cell-like cancers maintain histotype-related clinicopathologic characteristics despite overlapping unique molecular features. From a therapeutic perspective, identification of tuft cell-like LCNECs might be crucial given their close kinship with tuft cell-like SCLC

Engineering of cartilage tissue constructs in a 3-dimensional perfusion bioreactor culture system under controlled oxygen tension

The most relevant results generated in this thesis can be summarized as follow: · Adult human articular chondrocytes (AHAC) from elderly individuals expanded in culture medium supplemented with the growth factors TGFβ-1, FGF-2 and PDGF and subsequently cultured in 3-d pellets had an enhanced chondrogenic capacity when exposed to more physiological (i.e. 5%) oxygen levels. · In correlation with the enhanced tissue forming capacity of AHAC from elderly donors under low oxygen tension, the mRNA expression levels of selective matrix degrading enzymes were reduced as compared to conventional in vitro oxygen culture condition. · We developed an integrated bioreactor system, which streamlines within a single device the phases of perfusion cell seeding and prolonged perfusion culture of cell seeded scaffolds in vitro. · The culturing of uniformly seeded adult human articular chondrocytes under direct perfusion, where cells are continuously exposed to a normoxic range of oxygen levels, can maintain a uniform distribution of viable cells throughout thick porous scaffolds as compared to statically cultured constructs. · The culturing of constructs uniformly seeded with adult human articular chondrocytes under a more physiological range of oxygen resulted in a higher chondrogenic differentiation as compared to culture under normoxic levels. Anyhow, this effect was less pronounced as compared to statically cultured cell constructs or micromass cell pellets, possibly due to the flow induced shear forces. · Reduced perfusion flow rates applied to chondrocytes on porous scaffolds significantly induced more cartilaginous tissue in the presents of low vs. high oxygen levels. However the effects of low oxygen were not as marked as in pellet culture