We present an improved procedure of generating initial conditions (ICs) for climate model hindcast experiments with specified sea surface temperature and sea ice. The motivation is to minimize errors ...in the ICs and lead to a better evaluation of atmospheric parameterizations' performance in the hindcast mode. We apply state variables (horizontal velocities, temperature, and specific humidity) from the operational analysis/reanalysis for the atmospheric initial states. Without a data assimilation system, we apply a two‐step process to obtain other necessary variables to initialize both the atmospheric (e.g., aerosols and clouds) and land models (e.g., soil moisture). First, we nudge only the model horizontal velocities toward operational analysis/reanalysis values, given a 6 h relaxation time scale, to obtain all necessary variables. Compared to the original strategy in which horizontal velocities, temperature, and specific humidity are nudged, the revised approach produces a better representation of initial aerosols and cloud fields which are more consistent and closer to observations and model's preferred climatology. Second, we obtain land ICs from an off‐line land model simulation forced with observed precipitation, winds, and surface fluxes. This approach produces more realistic soil moisture in the land ICs. With this refined procedure, the simulated precipitation, clouds, radiation, and surface air temperature over land are improved in the Day 2 mean hindcasts. Following this procedure, we propose a “Core” integration suite which provides an easily repeatable test allowing model developers to rapidly assess the impacts of various parameterization changes on the fidelity of modeled cloud‐associated processes relative to observations.
Key Points:
An improved hindcast approach is proposed for climate model hindcast experiments
This approach provides better initial conditions and improves the hindcasts
Model developers can easily assess their parameterizations using this approach
In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS ...trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity.
Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications.
Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038).
Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection.
The dormancy (DosR) regulon of Mycobacterium tuberculosis is expressed in vitro during hypoxia and low-dose nitric oxide stimulation. Tubercle bacilli are thought to encounter these conditions in ...humans during latent infection. In this study, immune responses were evaluated to 25 most strongly induced DosR-regulon-encoded proteins, referred to as latency antigens. Proliferation assays were performed using M. tuberculosis-specific T-cell lines and peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients, tuberculin skin test positive (TST+) individuals and uninfected controls. All 25 latency antigens were able to induce production of interferon-gamma (IFN-γ) by T-cell lines. Eighteen latency antigens were also recognized by PBMC of M. tuberculosis-infected individuals, which indicates expression of the DosR-regulon during natural infection. Differential analysis showed that TST+ individuals recognized more latency antigens and with a stronger cumulative IFN-γ response than TB patients, while the opposite profile was found for culture filtrate protein-10. In particular Rv1733c, Rv2029c, Rv2627c and Rv2628 induced strong IFN-γ responses in TST+ individuals, with 61%, 61%, 52% and 35% responders, respectively. In conclusion, several new M. tuberculosis antigens were identified within the DosR-regulon. Particularly strong IFN-γ responses to latency antigens were observed in latently infected individuals, suggesting that immune responses against these antigens may contribute to controlling latent M. tuberculosis infection.
In this paper, we discuss energy-efficiency improvements in core networks obtained as a result of work carried out by the GreenTouch consortium over a five-year period. A number of techniques that ...yield substantial energy savings in core networks were introduced, including (i) the use of improved network components with lower power consumption, (ii) putting idle components into sleep mode, (iii) optically bypassing intermediate routers, (iv) the use of mixed line rates, (v) placing resources for protection into a low power state when idle, (vi) optimization of the network physical topology, and (vii) the optimization of distributed clouds for content distribution and network equipment virtualization. These techniques are recommended as the main energy-efficiency improvement measures for 2020 core networks. A mixed integer linear programming optimization model combining all the aforementioned techniques was built to minimize energy consumption in the core network. We consider group 1 nations' traffic and place this traffic on a US continental network represented by the AT&T network topology. The projections of the 2020 equipment power consumption are based on two scenarios: a business as usual (BAU) scenario and a GreenTouch (GT) (i.e., BAU + GT) scenario. The results show that the 2020 BAU scenario improves the network energy efficiency by a factor of 4.23 x compared with the 2010 network as a result of the reduction in the network equipment power consumption. Considering the 2020 BAU + GT network, the network equipment improvements alone reduce network power by a factor of 20 x compared with the 2010 network. Including of all the BAU + GT energy-efficiency techniques yields a total energy efficiency improvement of 315×. We have also implemented an experimental demonstration that illustrates the feasibility of energy-efficient content distribution in IP/WDM networks.
Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that ...individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.
The Atacama Millimeter/submillimeter Array (ALMA) Phasing Project (APP) has developed and deployed the hardware and software necessary to coherently sum the signals of individual ALMA antennas and ...record the aggregate sum in Very Long Baseline Interferometry (VLBI) Data Exchange Format. These beamforming capabilities allow the ALMA array to collectively function as the equivalent of a single large aperture and participate in global VLBI arrays. The inclusion of phased ALMA in current VLBI networks operating at (sub)millimeter wavelengths provides an order of magnitude improvement in sensitivity, as well as enhancements in u-v coverage and north-south angular resolution. The availability of a phased ALMA enables a wide range of new ultra-high angular resolution science applications, including the resolution of supermassive black holes on event horizon scales and studies of the launch and collimation of astrophysical jets. It also provides a high-sensitivity aperture that may be used for investigations such as pulsar searches at high frequencies. This paper provides an overview of the ALMA Phasing System design, implementation, and performance characteristics.
We present the results of geochemical analysis of silver coinage issued by Rome and dated between the fourth and second century BCE, which are complemented by data of coinage issued by Carthage, the ...Brettii, and the Greek colony of Emporion. Each of these minting authorities represents one of the major parties involved in the struggle for hegemony in the fourth to second centuries BCE Western Mediterranean region. This study retraces how the metal supply shifts in response to the transforming power relations and how this change is related to Rome's rise to the virtually uncontested ruler of the region.
This study presents the results of compositional and lead isotopic analysis of coinage issued by the Greek colonies of Syracuse, Metapontum, Taras and Thurium in the fifth to third centuries bce. The ...data suggest that each colony in Magna Graecia, regardless of its motherland roots and despite ongoing conflicts between the cities, had access to the same silver, and that this supply was stable overall throughout their period of minting and issuing coinage. The paper retraces the silver sources of the colonies and points out a potential supply route for the metal. It includes a method development for a multi‐standard quantification approach for laser ablation‐inductively coupled‐mass spectrometry (LA‐ICP‐MS) analysis of silver.
Airway inflammation and remodeling are major features of chronic obstructive pulmonary disease (COPD), whereas pulmonary hypertension is a common comorbidity associated with a poor disease prognosis. ...Recent studies in animal models have indicated that increased arginase activity contributes to features of asthma, including allergen-induced airway eosinophilia and mucus hypersecretion. Although cigarette smoke and lipopolysaccharide (LPS), major risk factors for COPD, may increase arginase expression, the role of arginase in COPD is unknown. This study aimed to investigate the role of arginase in pulmonary inflammation and remodeling using an animal model of COPD. Guinea pigs were instilled intranasally with LPS or saline twice weekly for 12 weeks and pretreated by inhalation of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or vehicle. Repeated LPS exposure increased lung arginase activity, resulting in increased l-ornithine/l-arginine and l-ornithine/l-citrulline ratios. Both ratios were reversed by ABH. ABH inhibited the LPS-induced increases in pulmonary IL-8, neutrophils, and goblet cells as well as airway fibrosis. Remarkably, LPS-induced right ventricular hypertrophy, indicative of pulmonary hypertension, was prevented by ABH. Strong correlations were found between arginase activity and inflammation, airway remodeling, and right ventricular hypertrophy. Increased arginase activity contributes to pulmonary inflammation, airway remodeling, and right ventricular hypertrophy in a guinea pig model of COPD, indicating therapeutic potential for arginase inhibitors in this disease.
Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare ...coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo.
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