H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.

Analysis of protein expression in zebrafish during gonad differentiation by targeted proteomics

The molecular mechanisms governing sex determination and differentiation in the zebrafish (Danio rerio) are not fully understood. To gain more insights into the function of specific genes in these complex processes, the expression of multiple candidates needs to be assessed, preferably on the protein level. Here, we developed a targeted proteomics method based on selected reaction monitoring (SRM) to study the candidate sex-related proteins in zebrafish which were selected based on a global proteomics analysis of adult gonads and representational difference analysis of male and female DNA, as well as on published information on zebrafish and other vertebrates. We employed the developed SRM protocols to acquire time-resolved protein expression profiles during the gonad differentiation period in vas::EGFP transgenic zebrafish. Evidence on protein expression was obtained for the first time for several candidate genes previously studied only on the mRNA level or suggested by bioinformatic predictions. Tuba1b (tubulin alpha 1b), initially included in the study as one of the potential housekeeping proteins, was found to be preferentially expressed in the adult testis with nearly absent expression in the ovary. The revealed changes in protein expression patterns associated with gonad differentiation suggest that several of the examined proteins, especially Ilf2 and Ilf3 (interleukin enhancer-binding factors 2 and 3), Raldh3 (retinaldehyde dehydrogenase type 3), Zgc:195027 (low density lipoprotein-related receptor protein 3) and Sept5a (septin 5a), may play a specific role in the sexual differentiation in zebrafish.

Luminescence Enhancement after Adding Stoppers to Europium(III) Nanozeolite L

Stopper molecules attached to nanozeolite L (NZL) boost the luminescence of confined Eu3+-β-diketonate complexes. The mechanism that is responsible was elucidated by comparing two diketonate ligands of different pKa and two aromatic imines, and by applying stationary and time resolved spectroscopy. The result is that the presence of the imidazolium based stopper is favorable to the sustainable formation of Eu3+-β-diketonate complexes with high coordination by decreasing the proton strength inside the channels of NZL. A consequence is that strongly luminescent transparent films can be prepared using aqueous suspension of the stopper modified composites.

Terahertz macrospin dynamics in insulating ferrimagnets

We investigate numerically the excitation of nonlinear magnetic interactions in a ferrite material by an energetic pump pulse of terahertz (THz) radiation. The calculations are performed by solving the coupled Maxwell and Landau-Lifshitz-Gilbert differential equations. In a time-resolved THz pump/THz probe scheme, it is demonstrated that Faraday rotation of a delayed THz probe pulse can be used to map these interactions. Our study is motivated by the ability of soft x-ray free electron lasers to perform time-resolved imaging of the magnetization process at the submicrometer and subpicosecond length and time scales.

Diurnal cycle of fossil and nonfossil carbon using radiocarbon analyses during CalNex

Radiocarbon (14C) analysis is a unique tool to distinguish fossil/nonfossil sources of carbonaceous aerosols. We present 14C measurements of organic carbon (OC) and total carbon (TC) on highly time resolved filters (3–4 h, typically 12 h or longer have been reported) from 7 days collected during California Research at the Nexus of Air Quality and Climate Change (CalNex) 2010 in Pasadena. Average nonfossil contributions of 58% ± 15% and 51% ± 15% were found for OC and TC, respectively. Results indicate that nonfossil carbon is a major constituent of the background aerosol, evidenced by its nearly constant concentration (2–3 μgC m−3). Cooking is estimated to contribute at least 25% to nonfossil OC, underlining the importance of urban nonfossil OC sources. In contrast, fossil OC concentrations have prominent and consistent diurnal profiles, with significant afternoon enhancements (~3 μgC m−3), following the arrival of the western Los Angeles (LA) basin plume with the sea breeze. A corresponding increase in semivolatile oxygenated OC and organic vehicular emission markers and their photochemical reaction products occurs. This suggests that the increasing OC is mostly from fresh anthropogenic secondary OC (SOC) from mainly fossil precursors formed in the western LA basin plume. We note that in several European cities where the diesel passenger car fraction is higher, SOC is 20% less fossil, despite 2–3 times higher elemental carbon concentrations, suggesting that SOC formation from gasoline emissions most likely dominates over diesel in the LA basin. This would have significant implications for our understanding of the on-road vehicle contribution to ambient aerosols and merits further study.

Progressive Image Denoising

Image denoising continues to be an active research topic. Although state-of-the-art denoising methods are numerically impressive and approch theoretical limits, they suffer from visible artifacts.While they produce acceptable results for natural images, human eyes are less forgiving when viewing synthetic images. At the same time, current methods are becoming more complex, making analysis, and implementation difficult. We propose image denoising as a simple physical process, which progressively reduces noise by deterministic annealing. The results of our implementation are numerically and visually excellent. We further demonstrate that our method is particularly suited for synthetic images. Finally, we offer a new perspective on image denoising using robust estimators.

Methodology for GPS Synchronization Evaluation with High Accuracy

Clock synchronization in the order of nanoseconds is one of the critical factors for time-based localization. Currently used time synchronization methods are developed for the more relaxed needs of network operation. Their usability for positioning should be carefully evaluated. In this paper, we are particularly interested in GPS-based time synchronization. To judge its usability for localization we need a method that can evaluate the achieved time synchronization with nanosecond accuracy. Our method to evaluate the synchronization accuracy is inspired by signal processing algorithms and relies on fine grain time information. The method is able to calculate the clock offset and skew between devices with nanosecond accuracy in real time. It was implemented using software defined radio technology. We demonstrate that GPS-based synchronization suffers from remaining clock offset in the range of a few hundred of nanoseconds but the clock skew is negligible. Finally, we determine a corresponding lower bound on the expected positioning error.

Accurate rotational constant and bond lengths of hexafluorobenzene by femtosecond rotational Raman coherence spectroscopy and ab initio calculations

The gas-phase rotational motion of hexafluorobenzene has been measured in real time using femtosecond (fs) time-resolved rotational Raman coherence spectroscopy (RR-RCS) at T = 100 and 295 K. This four-wave mixing method allows to probe the rotation of non-polar gas-phase molecules with fs time resolution over times up to ∼5 ns. The ground state rotational constant of hexafluorobenzene is determined as B 0 = 1029.740(28) MHz (2σ uncertainty) from RR-RCS transients measured in a pulsed seeded supersonic jet, where essentially only the v = 0 state is populated. Using this B 0 value, RR-RCS measurements in a room temperature gas cell give the rotational constants B v of the five lowest-lying thermally populated vibrationally excited states ν7/8, ν9, ν11/12, ν13, and ν14/15. Their B v constants differ from B 0 by between −1.02 MHz and +2.23 MHz. Combining the B 0 with the results of all-electron coupled-cluster CCSD(T) calculations of Demaison et al. [Mol. Phys.111, 1539 (2013)] and of our own allow to determine the C-C and C-F semi-experimental equilibrium bond lengths r e(C-C) = 1.3866(3) Å and r e(C-F) = 1.3244(4) Å. These agree with the CCSD(T)/wCVQZ r e bond lengths calculated by Demaison et al. within ±0.0005 Å. We also calculate the semi-experimental thermally averaged bond lengths r g(C-C)=1.3907(3) Å and r g(C-F)=1.3250(4) Å. These are at least ten times more accurate than two sets of experimental gas-phase electron diffraction r g bond lengths measured in the 1960s.

Thermal dependence of luminescence lifetimes and radioluminescence in quartz

During time-resolved optical stimulation experiments (TR-OSL), one uses short light pulses to separate the stimulation and emission of luminescence in time. Experimental TR-OSL results show that the luminescence lifetime in quartz of sedimentary origin is independent of annealing temperature below 500 °C, but decreases monotonically thereafter. These results have been interpreted previously empirically on the basis of the existence of two separate luminescence centers LH and LL in quartz, each with its own distinct luminescence lifetime. Additional experimental evidence also supports the presence of a non-luminescent hole reservoir R, which plays a critical role in the predose effect in this material. This paper extends a recently published analytical model for thermal quenching in quartz, to include the two luminescence centers LH and LL, as well as the hole reservoir R. The new extended model involves localized electronic transitions between energy states within the two luminescence centers, and is described by a system of differential equations based on the Mott–Seitz mechanism of thermal quenching. It is shown that by using simplifying physical assumptions, one can obtain analytical solutions for the intensity of the light during a TR-OSL experiment carried out with previously annealed samples. These analytical expressions are found to be in good agreement with the numerical solutions of the equations. The results from the model are shown to be in quantitative agreement with published experimental data for commercially available quartz samples. Specifically the model describes the variation of the luminescence lifetimes with (a) annealing temperatures between room temperature and 900 °C, and (b) with stimulation temperatures between 20 and 200 °C. This paper also reports new radioluminescence (RL) measurements carried out using the same commercially available quartz samples. Gaussian deconvolution of the RL emission spectra was carried out using a total of seven emission bands between 1.5 and 4.5 eV, and the behavior of these bands was examined as a function of the annealing temperature. An emission band at ∼3.44 eV (360 nm) was found to be strongly enhanced when the annealing temperature was increased to 500 °C, and this band underwent a significant reduction in intensity with further increase in temperature. Furthermore, a new emission band at ∼3.73 eV (330 nm) became apparent for annealing temperatures in the range 600–700 °C. These new experimental results are discussed within the context of the model presented in this paper.

Differential recruitment of brain networks during visuospatial and color processing: Evidence from ERP microstates

Recent functional magnetic resonance imaging (fMRI) studies consistently revealed contributions of fronto-parietal and related networks to the execution of a visuospatial judgment task, the so-called "Clock Task". However, due to the low temporal resolution of fMRI, the exact cortical dynamics and timing of processing during task performance could not be resolved until now. In order to clarify the detailed cortical activity and temporal dynamics, 14 healthy subjects performed an established version of the "Clock Task", which comprises a visuospatial task (angle discrimination) and a control task (color discrimination) with the same stimulus material, in an electroencephalography (EEG) experiment. Based on the time-resolved analysis of network activations (microstate analysis), differences in timing between the angle compared to the color discrimination task were found after sensory processing in a time window starting around 200ms. Significant differences between the two tasks were observed in an analysis window from 192ms to 776ms. We divided this window in two parts: an early phase - from 192ms to ∼440ms, and a late phase - from ∼440ms to 776ms. For both tasks, the order of network activations and the types of networks were the same, but, in each phase, activations for the two conditions were dominated by differing network states with divergent temporal dynamics. Our results provide an important basis for the assessment of deviations in processing dynamics during visuospatial tasks in clinical populations.

Probing the Structure, Pseudorotation, and Radial Vibrations of Cyclopentane by Femtosecond Rotational Raman Coherence Spectroscopy

Femtosecond time-resolved Raman rotational coherence spectroscopy (RCS) is employed to determine accurate rotational, vibration–rotation coupling constants, and centrifugal distortion constants of cyclopentane (C⁵H¹⁰). Its lowest-frequency vibration is a pseudorotating ring deformation that interconverts 10 permutationally distinct but energetically degenerate “twist” minima interspersed by 10 “bent” conformers. While the individual twist and bent structures are polar asymmetric tops, the pseudorotation is fast on the time scale of external rotation, rendering cyclopentane a fluxionally nonpolar symmetric top molecule. The pseudorotational level pattern corresponds to a one-dimensional internal rotor with a pseudorotation constant Bps ≈ 2.8 cm⁻¹. The pseudorotational levels are significantly populated up to l = ± 13 at 298 K; <10% of the molecules are in the l = 0 level. The next-higher vibration is the “radial” ν²³ ring deformation mode at 273 cm⁻¹, which is far above the pseudorotational fundamental. Femtosecond Raman RCS measurements were performed in a gas cell at T = 293 K and in a pulsed supersonic jet at T ≈ 90 K. The jet cooling reduces the pseudorotational distribution to l < ±8 and eliminates the population of ν²³, allowing one to determine the rotational constant as A0 = B0 = 6484.930(11) MHz. This value is ∼300 times more precise than the previous value. The fit of the RCS transients reveals that the rotation–pseudorotation coupling constant αe,psB = −0.00070(1) MHz is diminutive, implying that excitation of the pseudorotation has virtually no effect on the B0 rotational constant of cyclopentane. The smallness of αe,psB can be realized when comparing to the vibration–rotation coupling constant of the ν²³ vibration, αe,23B = −9.547(1) MHz, which is about 10⁴ times larger.

Noninvasive 4D pressure difference mapping derived from 4D flow MRI in patients with repaired aortic coarctation: comparison with young healthy volunteers

To assess spatial and temporal pressure characteristics in patients with repaired aortic coarctation compared to young healthy volunteers using time-resolved velocity-encoded three-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) and derived 4D pressure difference maps. After in vitro validation against invasive catheterization as gold standard, 4D flow MRI of the thoracic aorta was performed at 1.5T in 13 consecutive patients after aortic coarctation repair without recoarctation and 13 healthy volunteers. Using in-house developed processing software, 4D pressure difference maps were computed based on the Navier-Stokes equation. Pressure difference amplitudes, maximum slope of pressure amplitudes and spatial pressure range at mid systole were retrospectively measured by three readers, and twice by one reader to assess inter- and intraobserver agreement. In vitro, pressure differences derived from 4D flow MRI showed excellent agreement to invasive catheter measurements. In vivo, pressure difference amplitudes, maximum slope of pressure difference amplitudes and spatial pressure range at mid systole were significantly increased in patients compared to volunteers in the aortic arch, the proximal descending and the distal descending thoracic aorta (p < 0.05). Greatest differences occurred in the proximal descending aorta with values of the three parameters for patients versus volunteers being 19.7 ± 7.5 versus 10.0 ± 2.0 (p < 0.001), 10.9 ± 10.4 versus 1.9 ± 0.4 (p = 0.002), and 8.7 ± 6.3 versus 1.6 ± 0.9 (p < 0.001). Inter- and intraobserver agreements were excellent (p < 0.001). Noninvasive 4D pressure difference mapping derived from 4D flow MRI enables detection of altered intraluminal aortic pressures and showed significant spatial and temporal changes in patients with repaired aortic coarctation.

Improving 4D plan quality for PBS-based liver tumour treatments by combining online image guided beam gating with rescanning.

Pencil beam scanned (PBS) proton therapy has many advantages over conventional radiotherapy, but its effectiveness for treating mobile tumours remains questionable. Gating dose delivery to the breathing pattern is a well-developed method in conventional radiotherapy for mitigating tumour-motion, but its clinical efficiency for PBS proton therapy is not yet well documented. In this study, the dosimetric benefits and the treatment efficiency of beam gating for PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data sets, which give realistic 4DCT extracting motion information from 4DMRI. The value of 4DCT(MRI) is its capability of providing not only patient geometries and deformable breathing characteristics, but also includes variations in the breathing patterns between breathing cycles. In order to monitor target motion and derive a gating signal, we simulate time-resolved beams' eye view (BEV) x-ray images as an online motion surrogate. 4DDCs have been performed using three amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived from either pre-implanted fiducial markers or the diaphragm. In addition, gating has also been simulated in combination with up to 19 times rescanning using either volumetric or layered approaches. The quality of the resulting 4DDC plans has been quantified in terms of the plan homogeneity index (HI), total treatment time and duty cycle. Results show that neither beam gating nor rescanning alone can fully retrieve the plan homogeneity of the static reference plan. Especially for variable breathing patterns, reductions of the effective duty cycle to as low as 10% have been observed with the smallest gating rescanning window (3 mm), implying that gating on its own for such cases would result in much longer treatment times. In addition, when rescanning is applied on its own, large differences between volumetric and layered rescanning have been observed as a function of increasing number of re-scans. However, once gating and rescanning is combined, HI to within 2% of the static plan could be achieved in the clinical target volume, with only moderately prolonged treatment times, irrespective of the rescanning strategy used. Moreover, these results are independent of the motion surrogate used. In conclusion, our results suggest image guided beam gating, combined with rescanning, is a feasible, effective and efficient motion mitigation approach for PBS-based liver tumour treatments.

Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to nitazoxanide and metronidazole.

OBJECTIVES The characterization of differential gene expression in Giardia lamblia WB C6 strain C4 resistant to metronidazole and nitazoxanide using microarray technology and quantitative real-time PCR. METHODS In a previous study, we created and characterized the G. lamblia WB C6 clone C4 resistant to nitazoxanide and metronidazole. In this study, using a microarray-based approach, we have identified open-reading frames (ORFs) that were differentially expressed in C4 when compared with its wild-type WB C6. Using quantitative real-time PCR, we have validated the expression patterns of some of those ORFs, focusing on chaperones such as heat-shock proteins in wild-type and C4 trophozoites. In order to induce an antigenic shift, trophozoites of both strains were subjected to a cycle of en- and excystation. Expression of selected genes and resistance to nitazoxanide and metronidazole were investigated after this cycle. RESULTS Forty of a total of 9115 ORFs were found to be up-regulated and 46 to be down-regulated in C4 when compared with wild-type. After a cycle of en- and excystation, resistance of C4 to nitazoxanide and metronidazole was lost. Resistance formation and en-/excystation were correlated with changes in expression of ORFs encoding for major surface antigens such as the variant surface protein TSA417 or AS7 ('antigenic shift'). Moreover, expression patterns of the cytosolic heat-shock protein HSP70 B2, HSP40, and of the previously identified nitazoxanide-binding proteins nitroreductase and protein disulphide isomerase PDI4 were correlated with resistance and loss of resistance after en-/excystation. C4 trophozoites had a higher thermotolerance level than wild-type trophozoites. After en-/excystation, this tolerance was lost. CONCLUSIONS These results suggest that resistance formation in Giardia to nitazoxanide and metronidazole is correlated with altered expression of genes involved in stress response such as heat-shock proteins.