Electromechanical drilling of a 300 m core in a dry hole at Summit, Greenland

During the EUROCORE project in 1989 at Summit, Central Greenland, a 304.8-m long ice core of 105mm diameter was retrieved with an electromechanical drill. A dry drilling technique was used in order to minimise contamination of the ice. A special drill head with a small chipping depth was designed to assure minimal fracturing of the core. The quality was excellent to the depth of 180m, but then deteriorated due to increasing brittleness of the ice. Down to 280m we were able to maintain the mean length of unbroken core pieces above 0.1m by reducing the pitch from 7 to 2mm. The sticking of the consequently finer chips to the drill barrels was reduced by treating the barrels repeatedly with a silicone-based wax solution. Hole enlargement cutters near the upper end of the drill head prevented the drill from becoming stuck due to borehole closure

In situ analysis of transforming growth factor-βs (TGF-β1, TGF-β2, TGF-β3and TGF-3 type II receptor expression in malignant melanoma

We have analysed, by in situ hybridization, mRNA expression of TGF-β1, TGF-β2, TGF-β3, and of TGF-β type II receptor in benign melanocytic naevi, primary melanomas, and in skin metastases of malignant melanomas. Our results show that melanoma progression correlates with overexpression of TGF-β. All skin metastases and most primary melanomas invasive to Clark's level IV-V revealed specific TGF-β2 mRNA and protein expression. However, expression of this cytokine was not observed in benign melanocytic lesions and was detected only in one of five early primary melanomas investigated. Some primary melanomas and skin metastases also revealed specific TGF-β1 mRNA signals although expression of this isoform was not found in benign naevi. TGF-β3 expression, which was only barely detectable in benign melanocytic lesions, was enhanced in some skin metastases. Interestingly, the epidermis overlaying melanomas revealed lower levels of TGF-β3 mRNA expression than epidermis of healthy skin or epidermis adjacent to benign naevi, thereby suggesting that paracrine mechanisms between tumour cells and keratinocytes may influence melanoma development. In primary melanomas TGF-β type II receptor mRNA signals were much more heterogeneously distributed when compared to benign melanocytic naevi, suggesting variable degrees of TGF-β resistance among melanoma cells within individual lesions. However, melanoma progression appeared not to be correlated with a complete loss of TGF-β type II receptor gene expression, since all skin metastases revealed clearly detectable although heterogeneous levels of TGF-β type II receptor mRNA expressio

Rancang Bangun Mesin Ball Mill Untuk Memperkecil Partikel Pasir Silica Bekas Inti Cor

Banyaknya industri yang bergerak dalam bidang pengecoran logam, bayak menyisakan pasir silica bekas inti cor logam, dikarenakan pasir silica yang sudah digunakan sebagai inti cor sudah tidak dapat digunakan kembali, sehingga para usaha industri pengecoran harus membeli pasir silika untuk proses pengecoran berikutnya. Salah satu cara agar pasir silika bekas inti cor dapat digunkan kembali adalah dengan cara mendaur ulang pasir tersebut. Oleh karena itu inovasi pengolahan limbah pasir silika bekas inti menggunakan mesin penghancur dan penghalus pasir dengan menggunakan mesin ball mill. Rancang bangun mesin ball mill ini berfungsi untuk menghancurkan dan memperhalus pasir silica bekas inti, dengan cara pasir silika yang berada pada drum mesin ball mill akan digiling dan ditumbuk menggunakan bola baja yang mempunyai diameter yang berbeda. Prinsip kerja mesin ball mill adalah ketika drum yang berisi limbah pasir inti dan bola baja di putar maka bola baja akan bergesekan dan berbenturan yang mengakibatkan berubahnya bentuk pasir yang awalnya berupa bongkahan menjadi halus dan partikel pasir semakin kecil, maka akan bisa digunakan kembali karena partikel pasir lebih kecil dan daya ikat antara partikel semakin besar. Mekanisme mesin ball mill ini dirancang untuk menghancurkan dan memperhalus pasir silica bekas inti cor secara cepat dan merata, dengan menggunakan bola baja berdiameter 20 mm dan 25 mm, jumlah bola baja yang digunakan bervariasi serta pada penggilingan menggunakan variasi putaran

Estimation of Absolute Scale in Monocular SLAM Using Synthetic Data

This paper addresses the problem of scale estimation in monocular SLAM by estimating absolute distances between camera centers of consecutive image frames. These estimates would improve the overall performance of classical (not deep) SLAM systems and allow metric feature locations to be recovered from a single monocular camera. We propose several network architectures that lead to an improvement of scale estimation accuracy over the state of the art. In addition, we exploit a possibility to train the neural network only with synthetic data derived from a computer graphics simulator. Our key insight is that, using only synthetic training inputs, we can achieve similar scale estimation accuracy as that obtained from real data. This fact indicates that fully annotated simulated data is a viable alternative to existing deep-learning-based SLAM systems trained on real (unlabeled) data. Our experiments with unsupervised domain adaptation also show that the difference in visual appearance between simulated and real data does not affect scale estimation results. Our method operates with low-resolution images (0.03MP), which makes it practical for real-time SLAM applications with a monocular camera

Topical bioavailability of triamcinolone acetonide: effect of dose and application frequency

The application frequency of topical corticosteroids is a recurrently debated topic. Multiple-daily applications are common, although a superior efficacy compared to once-daily application is not unequivocally proven. Only few pharmacokinetic studies investigating application frequency exist. The aim of the study was to investigate the effect of dose (Experiment 1) and application frequency (Experiment 2) on the penetration of triamcinolone acetonide (TACA) into human stratum corneum (SC) in vivo. The experiments were conducted on the forearms of 15 healthy volunteers. In Experiment 1, single TACA doses (300μg/cm2 and 100μg/cm2) dissolved in acetone were applied on three sites per arm. In experiment 2, single (1×300μg/cm2) and multiple (3×100μg/cm2) TACA doses were similarly applied. SC samples were harvested by tape stripping after 0.5, 4 and 24h (Experiment 1) and after 4, 8 and 24h (Experiment 2). Corneocytes and TACA were quantified by UV/VIS spectroscopy and HPLC, respectively. TACA amounts penetrated into SC were statistically evaluated by a paired-sample t-test. In Experiment 1, TACA amounts within SC after application of 1×300μg/cm2 compared to 1×100μg/cm2 were only significantly different directly after application and similar at 4 and 24h. In Experiment 2, multiple applications of 3×100μg/cm2 yielded higher TACA amounts compared to a single application of 1×300μg/cm2 at 4 and 8h. At 24h, no difference was observed. In conclusion, using this simple vehicle, considerable TACA amounts were retained within SC independently of dose and application frequency. A low TACA dose applied once should be preferred to a high dose, which may promote higher systemic exposur

Correction: TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP.

The original version of this article contained an error in the name of one of the co-authors (Erika Owsley). This has been corrected in the PDF and HTML versions

TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP.

The pediatric immune deficiency X-linked proliferative disease-2 (XLP-2) is a unique disease, with patients presenting with either hemophagocytic lymphohistiocytosis (HLH) or intestinal bowel disease (IBD). Interestingly, XLP-2 patients display high levels of IL-18 in the serum even while in stable condition, presumably through spontaneous inflammasome activation. Recent data suggests that LPS stimulation can trigger inflammasome activation through a TNFR2/TNF/TNFR1 mediated loop in xiap-/- macrophages. Yet, the direct role TNFR2-specific activation plays in the absence of XIAP is unknown. We found TNFR2-specific activation leads to cell death in xiap-/- myeloid cells, particularly in the absence of the RING domain. RIPK1 kinase activity downstream of TNFR2 resulted in a TNF/TNFR1 cell death, independent of necroptosis. TNFR2-specific activation leads to a similar inflammatory NF-kB driven transcriptional profile as TNFR1 activation with the exception of upregulation of NLRP3 and caspase-11. Activation and upregulation of the canonical inflammasome upon loss of XIAP was mediated by RIPK1 kinase activity and ROS production. While both the inhibition of RIPK1 kinase activity and ROS production reduced cell death, as well as release of IL-1β, the release of IL-18 was not reduced to basal levels. This study supports targeting TNFR2 specifically to reduce IL-18 release in XLP-2 patients and to reduce priming of the inflammasome components

Dying for change: A roadmap to refine the fish acute toxicity test after 40 years of applying a lethal endpoint

The fish acute toxicity test (TG203; OECD, 2019) is frequently used and highly embedded in hazard and risk assessment globally. The test estimates the concentration of a chemical that kills 50% of the fish (LC50) over a 96 h exposure and is considered one of the most severe scientific procedures undertaken. Over the years, discussions at the Organisation for Economic Co-operation and Development (OECD) have resulted in changes to the test which reduce the number of fish used, as well as the development of a (potential) replacement test (TG236, OECD, 2013). However, refinement of the mortality endpoint with an earlier (moribundity) endpoint was not considered feasible during the Test Guideline’s (TG) last update in 2019. Several stakeholders met at a UK-based workshop to discuss how TG203 can be refined, and identified two key opportunities to reduce fish suffering: (1) application of clinical signs that predict mortality and (2) shortening the test duration. However, several aspects need to be addressed before these refinements can be adopted. TG203 has required recording of major categories of sublethal clinical signs since its conception, with the option to record more detailed signs introduced in the 2019 update. However, in the absence of guidance, differences in identification, recording and reporting of clinical signs between technicians and laboratories is likely to have generated piecemeal data of varying quality. Harmonisation of reporting templates, and training in clinical sign recognition and recording are needed to standardise clinical sign data. This is critical to enable robust data-driven detection of clinical signs that predict mortality. Discussions suggested that the 96 h duration of TG203 cannot stand up to scientific scrutiny. Feedback and data from UK contract research organisations (CROs) conducting the test were that a substantial proportion of mortalities occur in the first 24 h. Refinement of TG203 by shortening the test duration would reduce suffering (and test failure rate) but requires a mechanism to correct new results to previous 96 h LC50 data. The actions needed to implement both refinement opportunities are summarised here within a roadmap. A shift in regulatory assessment, where the 96 h LC50 is a familiar base for decisions, will also be critical

Core drilling through a temperate alpine glacier (Vernagtferner, Oetztal Alps) in 1979

In 1979 a core drilling project was carried out on Vernagtferner in the Oetztal Alps (Austria). This report describes the field work of the drilling project, the recovered core material and the occurrence of water in the boreholes and compiles the succeding investigation program