We present free energy estimates of nine 3-amidinobenzyl-1H-indole-2-carboxamide inhibitors of factor Xa. Using alchemical thermodynamic integration (TI) calculations, we estimate the difference in binding free energies with high accuracy and precision, except for mutations involving one of the amidinobenzyl rings. Crystal studies show that the inhibitors may bind in two distinct conformations, an

Introduction: Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement. The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT). Methods: Infor

The occupancy level of dwellings is an important parameter to know to determine the energy efficiency, energy use and indoor air quality, especially in low-energy buildings where the user-related energy uses, such as household electricity and domestic hot water heating, are significant parts of the energy balance in a building. For residential buildings, there is a lack of occupancy level data, wh

Background Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall an

The p(T)-differential production cross section of electrons from semileptonic decays of heavy-flavor hadrons has been measured at midrapidity in proton-proton collisions at root s = 2.76 TeV in the transverse momentum range 0.5 < p(T) < 12 GeV/c with the ALICE detector at the LHC. The analysis was performed using minimum bias events and events triggered by the electromagnetic calorimeter. Predicti

The purpose of this paper is to discuss and highlight how Cultural-Historical Activity Theory (CHAT) can contribute to the understanding of the different factors at play when a person is using augmentative and alternative communication (AAC). It is based on data from a 3-year project concerning activity-based vocabulary design of voice output communication aids (VOCAs). Four persons who used AAC a

Abstract in UndeterminedTo what extent were land markets the cause of Spanish agrarian backwardness? To address this unresolved issue, this paper uses new provincial data on average real land prices, together with a province-level variation in land productivity, to analyze the efficiency of land markets. Specifically, we test, first, whether land markets were spatially integrated and, secondly, wh

In the quest to decipher disease-associated biomarkers, miniaturized and multiplexed antibody arrays may play a central role in generating protein expression profiles, or protein maps, of crude serum samples. In this conceptual study, we explored a novel, 4-times larger pen design, enabling us to, in a unique manner, simultaneously print 48 different reagents (antibodies) as individual 78.5 μm(2)

The issue of whether major and rapid global sea-level changes existed on a preglacial Earth can be resolved by the detailed study of the Paleocene-Eocene (P-E) interval, where a large and rapid carbon isotope excursion linked to an important global warming event, the Paleocene Eocene Thermal Maximum, allows for high-resolution correlation between terrestrial, coastal and marine settings. Based pri

PURPOSETo assess children's trust in the care provided to a dying parent during the final week of life in relation to end-of-life medical information about disease, treatment, and death. METHODSThis nationwide population-based survey included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16 years, lost a parent to cancer. We asked about the children's reception of end-of-life pro

Large eddy simulation of diesel spray in a constant volume vessel as well as in an internal combustion engine has been performed. Spray is modeled using Eulerian-Lagrangian approach. The modeling involves primary and secondary break-up, the spray-induced turbulence (SIT) and the stochastic turbulence dispersion (STD) of parcels. Including SIT, based on Baharawaj et al. (2009), in coarse grids, e.g

Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson's disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared 43 patients o

One way to cool gas turbine tips is to design serpentine passages with 180A degrees turns inside the blades to fully utilize the coolant potential. It is therefore a desire to improve the cooling of the blade tips to ensure a long durability and safe operation. In the present work, a two-pass channel with a 180A degrees turn and various arrays of pin-fins mounted internally on the tip-cap is consi

Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule-delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that c

Substantial variation in milk coagulation properties has been observed among dairy cows. Consequently, raw milk from individual cows and breeds exhibits distinct coagulation capacities that potentially affect the technological properties and milk processing into cheese. This variation is largely influenced by protein composition, which is in turn affected by underlying genetic polymorphisms in the

To assess the prevalence of chronic obstructive pulmonary disease (COPD) in patients with primary Sjögren syndrome (pSS) and to study the association of COPD with cigarette smoking, radiographic features, respiratory symptoms, disease activity, and laboratory inflammatory and serological features in patients with pSS.

Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of

Large changes in solar ultraviolet radiation can indirectly affect climate(1) by inducing atmospheric changes. Specifically, it has been suggested that centennial-scale climate variability during the Holocene epoch was controlled by the Sun(2,3). However, the amplitude of solar forcing is small when compared with the climatic effects and, without reliable data sets, it is unclear which feedback me