On time-horizons based post-processing of flow forecasts

Post-processing raw stream flow forecasts are generally understood as estimating the univariate predictive density of stage or discharge values at selected future time steps, which is conditional on a single or multiple streamflow forecasts and observations up to the forecast start time to. The predictive density indicates to a forecaster in the most comprehensive way which flood level is likely to be expected. To this end, a variety of post-processing methods were proposed, which have respective strengths and weaknesses. These methods focus near-exclusively on the probabilistic forecast of the predictand at a single set future time ti, without addressing the predictive capability over the sequence of temporal sub-horizons (to, t1] ⊂ (to, t2] ⊂ … ⊂ (to, tk] nested into the overall forecast horizon. Here, we demonstrate the advantages of time-horizon dependent processing of streamflow forecasts, which evaluates the evolution of the predictive density over the sub-horizons by considering the temporal correlation among forecast ensemble members in addition to their cross-correlation with observations. The resulting probabilistic forecast consists of a multivariate distribution of stages and/or discharges at lagged forecasting times. These multivariate predictive distributions have the advantage of providing the likelihood of exceeding a critical threshold during the forecasting horizon while simultaneously offering valuable insights into the expected time of such exceedance. This approach supports not only decisions on issuing timely flood warnings but also the planing and roll-out of mitigating actions

Quantum logic gates based on coherent electron transport in quantum wires

It is shown that the universal set of quantum logic gates can be realized using solid-state quantum bits based on coherent electron transport in quantum wires. The elementary quantum bits are realized with a proper design of two quantum wires coupled through a potential barrier Numerical simulations show that (a) a proper design of the coupling barrier allows one to realize any one-qbit rotation and (b) Coulomb interaction between two qbits of this kind allows the implementation of the CNOT gate. These systems are based on a mature technology and seem to be integrable with conventional electronics

Duodenal Gastrointestinal Stromal Tumor: A Rare Disease in a Young Adult Female Patient Presenting with Life-Threatening Hemorrhage

Duodenal gastrointestinal stromal tumors (dGISTs) may be a source of life-threatening hemorrhage that leads to emergency surgical care, precluding tumor staging and the planning of an elective treatment. In this study, we report a case of potentially lethal bleeding dGIST in a young woman successfully treated by an organ-preserving elective surgery after endoscopic and angiographic hemostasis. A 26-year-old female patient was admitted to the Emergency Unit of our hospital with the complaints of hematemesis and melena in the previous 12 h. An upper endoscopy showed a 4-cm submucosal lesion, between the 2nd and 3rd part of the duodenum, in the lateral wall, with massive bleeding arising from central ulceration. Hemostasis was initially achieved endoscopically and then optimized by transarterial embolization. After a contrast-enhanced CT, the patient underwent planning elective surgery. Intraoperatively, a 3-cm lesion was confirmed and resected by excision of the full-thickness duodenum with adequate free margins. Immunohistochemical analysis of the specimen revealed to be a dGIST, with a low mitotic count (<5 mitosis/50 high power field), and tumor necrosis present in <50% of the lesion. The patient had an uneventful course

Liver transplantation for hepatocellular carcinoma in a patient with a novel telomerase mutation and steatosis

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Intercomparison of Gridded Precipitation Datasets over a Sub-Region of the Central Himalaya and the Southwestern Tibetan Plateau

Precipitation is a central quantity of hydrometeorological research and applications. Especially in complex terrain, such as in High Mountain Asia (HMA), surface precipitation observations are scarce. Gridded precipitation products are one way to overcome the limitations of ground truth observations. They can provide datasets continuous in both space and time. However, there are many products available, which use various methods for data generation and lead to different precipitation values. In our study we compare nine different gridded precipitation products from different origins (ERA5, ERA5-Land, ERA-interim, HAR v2 10 km, HAR v2 2 km, JRA-55, MERRA-2, GPCC and PRETIP) over a subregion of the Central Himalaya and the Southwest Tibetan Plateau, from May to September 2017. Total spatially averaged precipitation over the study period ranged from 411 mm (GPCC) to 781 mm (ERA-Interim) with a mean value of 623 mm and a standard deviation of 132 mm. We found that the gridded products and the few observations, with few exceptions, are consistent among each other regarding precipitation variability and rough amount within the study area. It became obvious that higher grid resolution can resolve extreme precipitation much better, leading to overall lower mean precipitation spatially, but higher extreme precipitation events. We also found that generally high terrain complexity leads to larger differences in the amount of precipitation between products. Due to the considerable differences between products in space and time, we suggest carefully selecting the product used as input for any research application based on the type of application and specific research question. While coarse products such as ERA-Interim or ERA5 that cover long periods but have coarse grid resolution have previously shown to be able to capture long-term trends and help with identifying climate change features, this study suggests that more regional applications, such as glacier mass-balance modeling, require higher spatial resolution, as is reproduced, for example, in HAR v2 10 km.Peer Reviewe

Bupivacaine myotoxicity is mediated by mitochondria

Abstract We have investigated the effects of the myotoxic local anesthetic bupivacaine on rat skeletal muscle mitochondria and isolated myofibers from flexor digitorum brevis, extensor digitorum longus, soleus, and from the proximal, striated portion of the esophagus. In isolated mitochondria, bupivacaine caused a concentration-dependent mitochondrial depolarization and pyridine nucleotide oxidation, which were matched by an increased oxygen consumption at bupivacaine concentrations of 1.5 mm or less at pH 7.4, whereas respiration was inhibited at higher concentrations. As a consequence of depolarization, bupivacaine caused the opening of the permeability transition pore (PTP), a cyclosporin A-sensitive inner membrane channel that plays a key role in many forms of cell death. In intact flexor digitorum brevis fibers bupivacaine caused mitochondrial depolarization and pyridine nucleotides oxidation that were matched by increased concentrations of cytosolic free Ca2+, release of cytochrome c, and eventually, hypercontracture. Both mitochondrial depolarization and cytochrome c release were inhibited by cyclosporin A, indicating that PTP opening rather than bupivacaine as such was responsible for these events. Similar responses to bupivacaine were observed in the soleus, which is highly oxidative. In contrast, fibers from the esophagus (which we show to be more fatigable than flexor digitorum brevis fibers) and from the highly glycolytic extensor digitorum longus didn't undergo pyridine nucleotide oxidation upon the addition of bupivacaine and were resistant to bupivacaine toxicity. These results suggest that active oxidative metabolism is a key determinant in bupivacaine toxicity, that bupivacaine myotoxicity is a relevant model of mitochondrial dysfunction involving the PTP and Ca2+ dysregulation, and that it represents a promising system to test new PTP inhibitors that may prove relevant in spontaneous myopathies where mitochondria have long been suspected to play a role

Transcriptomic Analysis of Single Isolated Myofibers Identifies miR-27a-3p and miR-142-3p as Regulators of Metabolism in Skeletal Muscle

Summary: Skeletal muscle is composed of different myofiber types that preferentially use glucose or lipids for ATP production. How fuel preference is regulated in these post-mitotic cells is largely unknown, making this issue a key question in the fields of muscle and whole-body metabolism. Here, we show that microRNAs (miRNAs) play a role in defining myofiber metabolic profiles. mRNA and miRNA signatures of all myofiber types obtained at the single-cell level unveiled fiber-specific regulatory networks and identified two master miRNAs that coordinately control myofiber fuel preference and mitochondrial morphology. Our work provides a complete and integrated mouse myofiber type-specific catalog of gene and miRNA expression and establishes miR-27a-3p and miR-142-3p as regulators of lipid use in skeletal muscle. : Chemello et al. characterize coding mRNAs and non-coding microRNAs expressed by myofibers of hindlimb mouse muscles, identifying complex interactions between these molecules that modulate mitochondrial functions and muscle metabolism. They demonstrate that specific short non-coding RNAs influence the contractile fiber composition of skeletal muscles by modulating muscle metabolism. Keywords: single myofiber, skeletal muscle metabolism, mitochondria, miRNAs, lipid

Endoscopic Submucosal Dissection for Subepithelial Tumor Treatment in the Upper Digestive Tract: A Western, Multicenter Study

Background/aims: Endoscopic submucosal dissection (ESD) has been proposed for removal of gastrointestinal subepithelial tumors (GI-SETs), but data are still scanty. This study aimed to report a case series from a western country. Patients and methods: Data of patients with upper GI-SETs suitable for ESD removal observed in 4 centers were retrospectively reviewed. Before endoscopic procedure, the lesion was characterized by endosonographic evaluation, histology, and CT scan. The en bloc resection and the R0 resection rates were calculated, as well as incidence of complications, and the 1-year follow-up was reported. Results: Data of 84 patients with esophageal (N = 13), gastric (N = 61), and duodenal (N = 10) GI-SETs were collected. The mean diameter of lesions was 26 mm (range: 12-110 mm). There were 17 gastrointestinal stromal tumors, 12 neuroendocrine tumors, 35 leiomyomas, 18 lipomas, and 2 hamartomas. En bloc and R0 resection were achieved in 83 (98.8%) and in 80 (95.2%) patients, respectively. Overall, a complication occurred in 11 (13.1%) patients, including bleeding (N = 7) and perforation (N = 4). Endoscopic approach was successful in all bleedings, but 1 patient who required radiological embolization, and in 2 perforations, while surgery was performed in the other patients. Overall, a surgical approach was eventually needed in 5 (5.9%), including 3 in whom R0 resection failed and 2 with perforation. Conclusions: Our study found that ESD may be an effective and safe alternative to surgical intervention for both benign and localized malignant GI-SETs

TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma

: This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory's trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients