Offline parameter estimation using EnKF and maximum likelihood error covariance estimates: Application to a subgrid-scale orography parameterization

International audienceRecent works show that the parameters controlling the parameterizations of the physical processes in climate models can be estimated from observations using filtering techniques. In this paper, we propose an offline parameter estimation approach, without estimating the state of the climate model. It is based on the Ensemble Kalman Filter (EnKF) and an iterative estimation of the error covariance matrices and of the background state using a maximum likelihood algorithm. The technique is implemented in a subgrid-scale orography (SSO) parameterization scheme that works in a single vertical column. First, the parameter estimation technique is evaluated using twin experiments. Then, the technique is used with synthetic observations to estimate how the parameters of the SSO scheme should change when the resolution of the input orography dataset of a general circulation model is increased. Our analysis reveals that when the resolution of the orography dataset increases, the scheme should take into account the dynamical sheltering that can occur at low levels between mountain peaks located within the same gridbox area

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation

Modular Mass Spectrometric Tool for Analysis of Composition and Phosphorylation of Protein Complexes

The combination of high accuracy, sensitivity and speed of single and multiple-stage mass spectrometric analyses enables the collection of comprehensive sets of data containing detailed information about complex biological samples. To achieve these properties, we combined two high-performance matrix-assisted laser desorption ionization mass analyzers in one modular mass spectrometric tool, and applied this tool for dissecting the composition and post-translational modifications of protein complexes. As an example of this approach, we here present studies of the Saccharomyces cerevisiae anaphase-promoting complexes (APC) and elucidation of phosphorylation sites on its components. In general, the modular concept we describe could be useful for assembling mass spectrometers operating with both matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) ion sources into powerful mass spectrometric tools for the comprehensive analysis of complex biological samples

Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations

The mid-Holocene (6,000 years ago) is a standard experiment for the evaluation of the simulated response of global climate models using paleoclimate reconstructions. The latest mid-Holocene simulations are a contribution by the Palaeoclimate Model Intercomparison Project (PMIP4) to the current phase of the Coupled Model Intercomparison Project (CMIP6). Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the northern hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2 K cooler that the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Neither this difference nor the improvement in model complexity and resolution seems to improve the realism of the simulations. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on climate sensitivity and feedback strength

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

DataSheet_1_Promising clinical outcome after body gamma knife radiotherapy for mediastinal follicular dendritic cell sarcoma with thoracic spine invasion and iliac metastasis: A case report and literature review.docx

BackgroundFollicular dendritic cell sarcoma (FDCS) is a rare type of intermediate grade tumor. Mediastinal FDCS with spinal invasion has not been well described. The treatment options include surgical resection and radiation therapy. The body gamma knife is a stereotactic body radiotherapy (SBRT) technology that is widely used in China. The pathological evaluation of a bone lesion after a body gamma knife procedure has not been reported. Here, we report a case of a patient with FDCS with thoracic spine invasion and iliac metastasis treated with surgery and body gamma knife.Case summaryA 36-year-old male patient was hospitalized at Zhongshan Hospital, Fudan University, due to a gradually aggravated pain on the lateral side of the left scapula for 6 months. Imaging examination showed neoplastic lesions on the left side of C7-T2 invading the vertebral body of T1, T2, and caput costae of the second rib and suspected metastasis in the left ilium. FDCS was diagnosed after performing a computed tomography (CT)-guided core needle biopsy, and the thoracic lesion was surgically resected. The body gamma knife was used as an adjuvant radiotherapy for the thoracic lesion and a primary therapy for the left ilium lesion. Iliac bone lesion resection was performed at Zhongshan Hospital, Fudan University, 10 weeks after RT. Compared with the biopsy report, the body gamma knife treatment resulted in a pathological complete response (PCR). The magnetic resonance imaging (MRI) examinations showed stable disease of the thoracic lesion after body gamma knife radiosurgery.ConclusionThis case report describes the treatment of mediastinal FDCS with thoracic spinal invasion and iliac metastasis. The promising outcome suggests that separation surgery is an effective treatment option for mediastinal FDCS with spinal column invasion. It also demonstrates the application prospects of the body gamma knife treatment in malignant lesions of the axial bones.</p

Characterization of Soybean Protein Isolate-Food Polyphenol Interaction via Virtual Screening and Experimental Studies

(1) Background: Protein–polyphenol interactions have been widely studied regarding their influence on the properties of both protein and the ligands. As an important protein material in the food industry, soybean protein isolate (SPI) experiences interesting changes through polyphenols binding. (2) Methods: In this study, a molecular docking and virtual screening method was established to evaluate the SPI–polyphenol interaction. A compound library composed of 33 commonly found food source polyphenols was used in virtual screening. The binding capacity of top-ranking polyphenols (rutin, procyanidin, cyanidin chloride, quercetin) was validated and compared by fluorescence assays. (3) Results: Four out of five top-ranking polyphenols in virtual screening were flavonoids, while phenolic acids exhibit low binding capacity. Hydrogen bonding and hydrophobic interactions were found to be dominant interactions involved in soybean protein–polyphenol binding. Cyanidin chloride exhibited the highest apparent binding constant (Ka), which was followed by quercetin, procyanidin, and rutin. Unlike others, procyanidin addition perturbed a red shift of SPI fluorescence, indicating a slight conformational change of SPI. (4) Conclusions: These results suggest that the pattern of SPI–polyphenol interaction is highly dependent on the detailed structure of polyphenols, which have important implications in uncovering the binding mechanism of SPI–polyphenol interaction

Soft tissue recurrence of giant cell tumor of the bone: Prevalence and radiographic features

Aim: Recurrence of giant cell tumor of bone (GCTB) in the soft tissue is rarely seen in the clinical practice. This study aims to determine the prevalence of soft tissue recurrence of GCTB, and to characterize its radiographic features. Methods: A total of 291 patients treated by intralesional curettage for histologically diagnosed GCTB were reviewed. 6 patients were identified to have the recurrence of GCTB in the soft tissue, all of whom had undergone marginal resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic features of soft tissue recurrence were classified into 3 types. Type I was defined as soft tissue recurrence with peripheral ossification, type II was defined as soft tissue recurrence with central ossification, and type III was defined as pure soft tissue recurrence without ossification. Demographic data including period of recurrence and follow-up duration after the second surgery were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate functional outcomes. Results: The overall recurrence rate was 2.1% (6/291). The mean interval between initial surgery and recurrence was 11.3 ± 4.1 months (range, 5â17). The recurrence lesions were located in the thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2 patients. According to the classification system mentioned above, 2 patients were classified with type I, 1 as type II and 3 as type III. After the marginal excision surgery, all patients were consistently followed up for a mean period of 13.4 ± 5.3 months (range, 6â19), with no recurrence observed at the final visit. All the patients were satisfied with the surgical outcome. According to the MSTS scale, the mean postoperative functional score was 28.0 ± 1.2 (range, 26â29). Conclusions: The classification of soft tissue recurrence of GCTB may be helpful for the surgeon to select the appropriate imaging procedure to detect the recurrence. In addition, the marginal resection can produce a favorable outcome for the patients. Keywords: Giant cell tumor of bone, Recurrence, Prevalence, Radiographic feature