DoorGym: A Scalable Door Opening Environment And Baseline Agent

In order to practically implement the door opening task, a policy ought to be robust to a wide distribution of door types and environment settings. Reinforcement Learning (RL) with Domain Randomization (DR) is a promising technique to enforce policy generalization, however, there are only a few accessible training environments that are inherently designed to train agents in domain randomized environments. We introduce DoorGym, an open-source door opening simulation framework designed to utilize domain randomization to train a stable policy. We intend for our environment to lie at the intersection of domain transfer, practical tasks, and realism. We also provide baseline Proximal Policy Optimization and Soft Actor-Critic implementations, which achieves success rates between 0% up to 95% for opening various types of doors in this environment. Moreover, the real-world transfer experiment shows the trained policy is able to work in the real world. Environment kit available here: https://github.com/PSVL/DoorGym/Comment: Full version (Real world transfer experiments result

Gastric undifferentiated carcinoma, INI1-negative

Among undifferentiated carcinomas of the digestive system (DS-UC), undifferentiated gastric carcinoma (GUC) is one of the rarest epithelial malignancies of the stomach, accounting for 0.1-0.3% of all gastric carcinomas.1 The limited data on DS-UC/GUC describe them as aggressive, usually at an advanced stage and with a marked tendency to lymph node metastasis, even when still intramucosal.1,2 While for other gastric neoplasms (both epithelial and lymphoid), there are definite etiological correlations, i.e., with infectious agents (Helicobacter pylori or EBV), both the etiology and the molecular pathways of GUC remain largely unknown: the few data available suggest dedifferentiation from a glandular neoplasm (indeed, cases are described in which areas of well-differentiated gastric adenocarcinoma coexist with GUC); however, this assumption is not always proved, neither from a morphological nor a molecular point of view. Other data indicate a correlation between the alteration of molecular pathways linked to the SWI/SNF chromatin-remodeling complex, with loss mainly of SMARCB1 (INI1) and some histological forms of GUC, in particular the rhabdoid histotype.3-6 Several variants of DS-UC/GUC are described: anaplastic with marked cellular pleomorphism, sarcomatoid, with osteoclast-like giant cells and lymphoepithelioma-like;1 however, the aforementioned INI1-negative rhabdoid is the most commonly reported histo-molecular variant, both in the stomach and in the whole digestive system.3-6 It is worth mentioning that the most frequent location of INI1-negative tumors is in the head and neck region, while gastroenteric ones are extremely rare.7 The photo above refers to an 84-year-old woman found unconscious at home due to an unknown cause. On admission to the hospital, jaundice and acute liver failure were observed together with the presence of a mesogastric mass strongly suspected on radiology to be neoplastic. Before any further diagnostic/therapeutic steps could be taken, death occurred. The autopsy reveals the presence of a large antral neoplasm with a maximum diameter of 5.5 cm (Figure 1A), with numerous perigastric and peripancreatic enlarged lymph nodes of metastatic significance. The voluminous neoplasia causes ab-extrinsic compression of the extrahepatic biliary tract, macroscopically justifying jaundice found at admission. The liver shows multiple intraparenchymal whitish dots, while the other organs examined, both abdominal (intra- and extraperitoneal) and thoracic and intracranial, show no significant macroscopic lesions. Figure 1 A - macroscopic view of the gastric mucosa with a large centrally depressed and ulcerated antral neoplasm (scale bar = 5 cm); B - photomicrograph of the gastric lesion, showing the presence of a neoplasm with atypical non-cohesive, round/rhabdoid cells, with scant cytoplasm and frequent mitotic figures (H&E, 60x); C - immunohistochemistry, showing focal positivity ‘dot-like’ for epithelial membrane antigen (EMA); D - immunohistochemistry of liver metastases, indicating loss of expression for INI1 in the neoplastic cells (on the left), whereas INI1 expression is retained in the nuclei of hepatocytes (on the right).: Microscopically, the neoplasm is composed of medium-sized undifferentiated/rhabdoid cells with numerous mitoses, intratumoral necrosis, and intermingled lymphocytes (Figure 1B). The neoplasm infiltrates the gastric wall also with serosa involvement and lymphatic and hematic embolization, which corresponds histologically to widespread lymph node and hepatic metastatic localization (the latter also explains the liver failure clinically observed). Immunohistochemistry shows a focal positivity for MNF116 broad-spectrum cytokeratins and a dot-like expression of EMA (Figure 1C) and Vimentin. At the same time, it is negative for muscle markers (Actin, Desmin, Myogenin, Calponin, and Caldesmon), neuroendocrine markers (Chromogranin, Synaptophysin, NSE, and CD56), hematolymphoid lineage markers (CD45, CD3, CD20, CD79alpha, CD68, CD138, MPO) and melanocytic markers (S100, Melan-A, HMB-45). EBV, CD99, CD117, SALL4, and Glypican3 were also negative. Finally, the absence of expression of INI1 (Figure 1D) is noteworthy. From a strictly microscopic point of view, the features of the neoplastic cells suggest the differential diagnosis between a GUC, an EBV-associated carcinoma with lymphoid stroma, an aggressive lymphoma, a metastatic melanoma, a germ cell neoplasm, a PEComa, and a rhabdomyosarcoma (or other types of sarcomas with epithelioid/rhabdoid pattern).1 Based on the overall immunomorphological data, which allows us to exclude the other aforementioned hypotheses, we make the final diagnosis of GUC with rhabdoid morphological aspects and, according to the literature, lack of immunophenotypic expression for INI1

Pathologist's approach to paediatric and neonatal eosinophilic gastrointestinal disorders

Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach. : Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist's ability in identifying an abnormal number of eosinophils in this setting of patients. : When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis. : Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like "with eosinophilic pattern" should be favoured over a specific diagnosis of "eosinophilic disorder" in order to avoid potential confusion between different entities

UTC and GNSS system time access using PPP with broadcast ephemerides

The application of precise point positioning with broadcast ephemerides (PPP-BCE) is discussed as an alternative to the established all-in-view technique for multi-GNSS time transfer. It combines the use of broadcast ephemerides with low-noise carrier-phase observations for accessing GNSS system time scales and Coordinated Universal Time (UTC) with improved precision, and can be employed on stationary as well as mobile receivers in offline or real-time analyses. Using calibrated timing receivers, the method is shown to provide estimates of the GNSS-to-GNSS time offsets (XYTOs) with an accuracy at the 2 ns level. In the absence of prior calibrations, 0.5 ns consistency across different stations is achieved for GPS, Galileo, and BeiDou-3 after adjustment of systematic biases in comparison with calibrated reference stations or broadcast XYTO values. Furthermore, access to GNSS-specific UTC realizations can be obtained through predictions of the UTC offset from GNSS system time as provided in the broadcast ephemerides of individual constellations. The overall quality of the PPP-BCE-derived receiver clock offsets from UTC is assessed using calibrated receivers at various timing laboratories along with BIPM-provided UTC-UTC(k) measurements. Over the 1.5 years covered in the study, an accuracy of 1.8 ns for GPS and 2.5 ns for Galileo is demonstrated. For BeiDou, a slightly worse accuracy of 3 ns is obtained for a single timing laboratory over 9 months

Biomechanical defects and rescue of cardiomyocytes expressing pathologic nuclear lamins

Given the clinical impact of LMNA cardiomyopathies, understanding lamin function will fulfill a clinical need and will lead to advancement in the treatment of heart failure. A multidisciplinary approach combining cell biology, atomic force microscopy (AFM) and molecular modeling was used to analyze the biomechanical properties of human lamin A/C gene (LMNA) mutations (E161K, D192G, N195K) using an in vitro neonatal rat ventricular myocyte (NRVM) model

The Cardiomyopathy Lamin A/C D192G Mutation Disrupts Whole-Cell Biomechanics in Cardiomyocytes as Measured by Atomic Force Microscopy Loading-Unloading Curve Analysis

Atomic force microscopy (AFM) cell loading/unloading curves were used to provide comprehensive insights into biomechanical behavior of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wall, myopathy and severe cardiomyopathy. Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls. Furthermore, there seems to be a connection between this lamin nuclear mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to-cell membrane adhesion. We believe that this loss of adhesion involves the cytoskeletal architecture since our microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the cytoskeleton. Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein. These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy, and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

The 10B(p,α)7Be S(E)-factor from 5 keV to 1.5 MeV using the Trojan Horse Method

The 10 B(p, α ) 7 Be reaction is the main responsible for the 10 B destruction in stellar interior [1]. In such environments this p-capture process occurs at a Gamow energy of 10 keV and takes places mainly through a resonant state (Ex = 8.701 MeV) of the compound 11 C nucleus. Thus a resonance right in the region of the Gamow peak is expected to significantly influence the behavior of the astrophysical S(E)-factor. The 10 B(p, α ) 7 Be reaction was studied via the Trojan Horse Method (THM) applied to the 2 H( 10 B, α 7 Be)n in order to extract the astrophysical S(E)-factor in a wide energy range from 5 keV to 1.5 MeV