Isotope shifts of 223–226,228Ra19F were measured for different vibrational levels in the electronic transition A2II1/2 ← X2Σ+. The observed isotope shifts demonstrate the particularly high ...sensitivity of radium monofluoride to nuclear size effects, offering a stringent test of models describing the electronic density within the radium nucleus. Ab initio quantum chemical calculations are in excellent agreement with experimental observations. These results highlight some of the unique opportunities that short-lived molecules could offer in nuclear structure and in fundamental symmetry studies.
A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung ...function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF.
A retrospective study was performed in 44 consecutive patients with CF aged 5-19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV1) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF75)) were recorded. Abnormal structure was defined as a composite HRCT score of >5%, the presence of bronchiectasis or air trapping >30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV1 or FEF75 below the predicted mean -1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done.
The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV1 and 62-75% for FEF75. Specificity was 43-65% for LCI, 89-100% for FEV1 and 75-88% for FEF75. LCI correlated better with HRCT scores (Rs +0.85) than FEV1 (-0.62) or FEF75 (-0.66).
LCI is a more sensitive indicator than FEV1 or FEF75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles ...in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90m3 and is operated in a 0.5T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
To investigate the influence of climatic conditions and season on milk composition, bulk tank milk was sampled on 5 occasions during a period of 15 mo from 20 Swedish dairy farms. These farms ...included 5 organic and 5 conventional farms in central Sweden and 7 traditional conventional farms and 3 conventional farms growing maize for silage in southern Sweden. Feed data and milk yield were recorded and milk was analyzed for content of fatty acids, carotenoids, and tocopherol. Differences between milk from the 2 regions and between summer and winter seasons were shown. Milk from central Sweden differed from milk from southern Sweden in that it had a higher content of carotenoids, tocopherol, short-chain fatty acids (C4–C14), C18:0, and C18:3 n-3 and a lower content of C16. Summer milk samples had a lower fat content and contained higher amounts of C18:1 cis-9 and conjugated linoleic acid cis-9,trans-11, and lower amounts of C4 to C16 compared with winter milk. Differences between farm types from central Sweden were lower content of conjugated linoleic acid cis-9,trans-11 and higher content of C18:3 n-3 in organic milk compared with conventional milk. In southern Sweden the use of maize silage caused lower milk content of carotenoids and C18:3 n-3 when compared with traditional feeding. Differences in milk composition could be related to climatic differences because legumes are more dominating in the leys of central Sweden and maize growing is limited to southern Sweden.
The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anti-cancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA ...double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-γH2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins. PFKFB3 relocalization is critical for recruitment of HR proteins, HR activity, and cell survival upon IR. We develop KAN0438757, a small molecule inhibitor that potently targets PFKFB3. Pharmacological PFKFB3 inhibition impairs recruitment of ribonucleotide reductase M2 and deoxynucleotide incorporation upon DNA repair, and reduces dNTP levels. Importantly, KAN0438757 induces radiosensitization in transformed cells while leaving non-transformed cells unaffected. In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer.
In this work, an experimental method for measuring the bulk properties and fracture loading relations for iron ore pellets is presented. Knowledge on the bulk behaviour and fracture data for iron ore ...pellets is of great importance for improving the material transportation systems and to increase the product quality. Trustworthy numerical simulations of iron ore pellets also demand reliable material data for the models. Here, instrumented confined compression tests are carried out at different load levels. Measurement data of the axial and radial stresses and the axial displacement are recorded for each test. Measurements of fractured iron ore pellets are carried out at different loads giving rise to crushing up to 20% of the total material. From the measured data, the Poisson's ratio, the bulk modulus and a plastic strain hardening function are determined. In addition, friction measurements of iron ore pellets are carried out at different loads and configurations. In conclusion, the test method developed here is usable for the determination of the bulk properties and fracture characteristics of iron ore pellets.
An experimental method for measuring the bulk properties and a fracture load relation for iron ore pellets is presented. The Poisson's ratio, the bulk modulus and a plastic strain hardening function for iron ore pellets are determined from the tests. A fracture–load relation for iron ore pellets are determined up to 20% crushed material. Display omitted
► An experimental method for iron ore pellets measurements is developed. ► Bulk properties and fracture data for iron ore pellets are measured. ► Poisson's ratio, bulk modulus and a plastic hardening function are determined. ► A fracture–load relation is also established.
Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, andWnt16−/−
mice have reduced cortical bone mass. AsWnt16expression is ...enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females isWNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblasticWnt16expression or noWnt16expression. We developed a mouse model with osteoblast-specificWnt16overexpression (Obl-Wnt16). These mice had several-fold elevatedWnt16expression in both trabecular and cortical bone compared with wild type (WT) mice.Obl-Wnt16mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L₃. Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree inObl-Wnt16mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovxObl-Wnt16mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated inWnt16−/−
mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in bothWnt16−/−
and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16-targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.
Citrobacter rodentium is an attaching and effacing pathogen used as a murine model for enteropathogenic Escherichia coli. The mucus layers are a complex matrix of molecules, and mucus swelling, ...hydration and permeability are affected by many factors, including ion composition. Here, we used the C. rodentium model to investigate mucus dynamics during infection. By measuring the mucus layer thickness in tissue explants during infection, we demonstrated that the thickness changes dynamically during the course of infection and that its thickest stage coincides with the start of a decrease of bacterial density at day 14 after infection. Although quantitative PCR analysis demonstrated that mucin mRNA increases during early infection, the increased mucus layer thickness late in infection was not explained by increased mRNA levels. Proteomic analysis of mucus did not demonstrate the appearance of additional mucins, but revealed an increased number of proteins involved in defense responses. Ussing chamber-based electrical measurements demonstrated that ion secretion was dynamically altered during the infection phases. Furthermore, the bicarbonate ion channel Bestrophin-2 mRNA nominally increased, whereas the Cftr mRNA decreased during the late infection clearance phase. Microscopy of Muc2 immunostained tissues suggested that the inner striated mucus layer present in the healthy colon was scarce during the time point of most severe infection (10 days post infection), but then expanded, albeit with a less structured appearance, during the expulsion phase. Together with previously published literature, the data implies a model for clearance where a change in secretion allows reformation of the mucus layer, displacing the pathogen to the outer mucus layer, where it is then outcompeted by the returning commensal flora. In conclusion, mucus and ion secretion are dynamically altered during the C. rodentium infection cycle.
A production technique with the capacity to significantly improve the mechanical properties of powder metallurgy (PM) parts is high-velocity compaction (HVC). To extend the usage of the HVC method, ...detailed knowledge of the HVC process is important. To facilitate the development of production processes, numerical simulations can be utilised. In the development of high-precision simulation models, constitutive data of HVC specimens at high strain rates are required. In this study, the dynamic compressive properties of cylindrical specimens made by HVC were measured using a split Hopkinson pressure bar (Kolsky bar) assembly. For this technique, a specimen is placed between two elastic bars. The impact loading is achieved by a projectile accelerating inside an air gun, which impacts the end of the input bar and generates elastic-wave propagation.
The powder material used for the experiments is a press-ready iron-based premix. Among specimens made by HVC and conventional compaction (CC), the effects of the specimen density and the strain rate on the compressive properties, such as failure stress, Young's modulus and failure behaviour, are investigated. During dynamic compression, the failure behaviour of the specimens was also recorded using a high-speed video camera. The difference in the mechanical behaviour between HVC-pressed specimens and conventionally pressed specimens are also investigated. The stress–strain curves of HVC-pressed specimens are identical to those of conventionally pressed specimens, but the failure behaviour differs are concluded.
A well-established numerical method for forming simulations also conducted for powder compaction is the finite element method (FEM). The impact loading of the powder is modelled and simulated using nonlinear three-dimensional FEM. To model the impact process, a constitutive relation for the powder behaviour is proposed, taking into account the strain rate and density variations. To capture the global response caused by cracking during impact, a damage model is implemented. The numerical results in terms of the stress and strain history in the specimen during impact are compared with the experimental measurements. In conclusion, the proposed material model captures the increase in the yield stress due to the higher strain rates and the decrease in stress due to cracking.
Display omitted
•The dynamic compressive properties of iron-powder compacts have been investigated.•The strain-rate dependence of the yield stress increases with the density.•A constitutive model is presented that considers the strain-rate dependence.•The proposed material model captures the strain rate behaviour in the material.
PDF
