Highly Ordered Monolayers of µm-Sized Polystyrene Spheres Studied by Grazing-Incidence Small-Angle X-ray Scattering, Simulations, and Geometrical Calculations.

Unraveling the two-dimensional (2D) structural ordering of colloidal particles assembled at a flat surface is essential for understanding and optimizing their physical properties. So far, grazing-incidence small-angle X-ray scattering (GISAXS) has been widely used to determine crystallographic information on 2D self-assembled structures of nanosize objects. However, solving the structure of 2D lattices consisting of micrometer (µm)-sized objects still remains a challenge using scattering methods. Here, a model 2D SCALMS (supported catalytically active liquid metal solution) template is fabricated from µm-sized polystyrene (PS) spheres that form a monolayer on top of the flat solid support. GISAXS patterns of the sample were collected for rotation angles around its surface normal in steps of 3°. For every rotation angle, different Bragg-type interference maxima along the out-of-plane (qz) direction were observed. On the basis of simulations of GISXAS patterns of single domains of ordered particle arrangements using the distorted wave Born approximation (DWBA) and validation against a simple geometrical scattering model, the interference maxima could nicely be interpreted to originate from a monolayer of the µm-sized spherical particles which are arranged in domains of hexagonal 2D paracrystalline order. This novel GISAXS evaluation technique serves as a proof of principle for determining the µm-size periodicity of 2D crystalline domains and demonstrates its potential to spatially resolve the relative orientations of such domains with respect to a reference direction.

Erratum: Fast Domain Wall Motion Governed by Topology and Œrsted Fields in Cylindrical Magnetic Nanowires [Phys. Rev. Lett. 123, 217201 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.217201.

Fast Domain Wall Motion Governed by Topology and Œrsted Fields in Cylindrical Magnetic Nanowires.

While the usual approach to tailor the behavior of condensed matter and nanosized systems is the choice of material or finite-size or interfacial effects, topology alone may be the key. In the context of the motion of magnetic domain walls (DWs), known to suffer from dynamic instabilities with low mobilities, we report unprecedented velocities >600 m/s for DWs driven by spin-transfer torques in cylindrical nanowires made of a standard ferromagnetic material. The reason is the robust stabilization of a DW type with a specific topology by the Œrsted field associated with the current. This opens the route to the realization of predicted new physics, such as the strong coupling of DWs with spin waves above >600 m/s.

Residue concentration of cefquinome after intramammary dry cow therapy and short dry periods.

Short dry periods and their effects on milk production, reproductive performance, as well as cow and udder health have been widely studied. A dearth of information is available about the consequences of short dry periods on the residue concentrations of dry cow antibiotics in milk after calving. The objective of our study was to determine the residue concentration of a dry cow antibiotic in milk after short dry periods during the colostrum period and early lactation. Quarters of 19 dry cows were treated with an intramammary (IMM) dry cow antibiotic containing 150 mg of cefquinome on d 21, 14, and 7 before calculated calving date. One quarter of each cow did not receive treatment and served as negative control. After calving, quarter foremilk samples were collected twice daily until 21 d and once daily until 36 d after IMM dry cow treatment (i.e., end of withdrawal period). A total of 588 foremilk samples from odd milking numbers were chosen for the determination of the residue concentration of cefquinome using HPLC-tandem mass spectrometry until the residue concentration fell below the limit of quantification (1 ng/g), which occurred at the latest in milking number 37. The dry period length of the treated quarters was categorized in 3 dry period groups ranging from 1 to 7 d (4.8 ± 2.4), 8 to 14 d (11.5 ± 2.3), and 15 to 26 d (19.5 ± 3.3; ±SEM), in dry period group 1, 2, and 3, respectively. In dry period group 1, the cefquinome concentration increased after calving until the third milking and decreased considerably until the fifth milking. In dry period group 2, the cefquinome concentration peaked at the second milking and decreased considerably until the fifth milking as well. There was no increase in cefquinome after calving in dry period group 3. Up to the 37th milking, the cefquinome concentration was higher in dry period group 1 than in dry period group 2 and 3. On average, 31.3 ± 1.2, 19.0 ± 1.1, and 6.7 ± 0.8 milkings and 19.4 ± 0.4, 20.6 ± 0.5, and 24.1 ± 0.7 d after treatment were necessary for the concentration of cefquinome to fall below the maximum residue limit (MRL) in dry period group 1, 2, and 3, respectively. These results indicate that shorter dry periods lead initially to higher cefquinome residues in milk. The residue concentration after experimental short dry periods still falls below the MRL within the recommended withdrawal period for milk of 36 d after IMM dry cow treatment. For the sake of food safety and economics, these short dry periods should not be used in the dry cow management, as they lead up to a maximum of 31.3 ± 1.2 milkings and 19.4 ± 0.4 d after treatment with cefquinome residues above the MRL. Therefore, a considerable number of milkings have to be discarded due to long withdrawal periods after calving.

Retention modes of manure-fecal coliforms in soil under saturated hydraulic condition.

Manures are important soil nutrient conditioners and source of several pathogenic bacteria that potentially contribute to groundwater and surface water pollution. The best management practices need a solid understanding of manure sources, concentrations, and strategies to limit the number of bacteria in natural soil environment. In this study, a series of soil column experiments were conducted to investigate how bacteria mobility can potentially be influenced by retention mechanisms while moving through undisturbed saturated soil. This was assessed by bacteria retention profiles and mobility indices including the maximum transported (Cmax-T) and retained (Cmax-R) concentrations, filtration coefficient (λf) and the maximum depth of bacteria transport (Zmax). Three different soil samples (sandy, loamy and silty clay loam) were enriched with three types of manures (cow, sheep, and poultry), placed on top of three soil columns (16 cm diameter, 30 cm height) with an equivalent of 10 Mg ha-1 (dry basis) summing up to a total of 36 columns. Leaching was performed under saturated steady-state conditions (i.e., 1.62 cm min-1) for a duration of 4 pore volumes. After percolation, soil columns were sliced into six 5-cm interval layers and slices were characterized for retained bacteria. Results showed irregular exponential or quasi-exponential bacteria retention profiles for cow and sheep manures, whereas uniform-shaped profiles occurred for poultry manure. The latter variant also switched to exponential shape for the sandy soil at the highest and lowest Cmax-T and Cmax-R values due to higher pore water velocity. The λf and the Zmax values were also found to be affected by soil texture and manure origin. The λf was higher for poultry manure due to higher free-cell transport of bacteria most probably induced by higher amount of soluble mobile components. However, the greater amounts of transported wooden materials released from cow and sheep manures acted as harbors for bacteria. Accordingly, the filtration rate decreased and tailing effects for bacteria transport increased. The results also suggest that the practices and strategies for using manures could be optimized according to the respective transport behavior to manage the bacteria retention with respect to soil and manure types to reduce soil and water pollution.

The clinical picture of cachexia: a mosaic of different parameters (experience of 503 patients).

BACKGROUND: Despite our growing knowledge about the pathomechanisms of cancer cachexia, a whole clinical picture of the cachectic patient is still missing. Our objective was to evaluate the clinical characteristics in cancer patients with and without cachexia to get the whole picture of a cachectic patient. METHODS: Cancer patients of the University Clinic "Klinikum rechts der Isar" with gastrointestinal, gynecological, hematopoietic, lung and some other tumors were offered the possibility to take part in the treatment concept including a nutrition intervention and an individual training program according to their capability. We now report on the first 503 patients at the time of inclusion in the program between March 2011 and October 2015. We described clinical characteristics such as physical activity, quality of life, clinical dates and food intake. RESULTS: Of 503 patients with cancer, 131 patients (26.0%) were identified as cachectic, 369 (73.4%) as non-cachectic. The change in cachexia were 23% reduced capacity performance (108 Watt for non-cachectic-patients and 83 Watt for cachectic patients) and 12% reduced relative performance (1.53 Watt/kg for non-cachectic and 1.34 Watt/kg for cachectic patients) in ergometry test. 75.6% of non-cachectic and 54.3% of cachectic patients still received curative treatment. CONCLUSION: Cancer cachectic patients have multiple symptoms such as anemia, impaired kidney function and impaired liver function with elements of mild cholestasis, lower performance and a poorer quality of life in the EORTC questionnaire. Our study reveals biochemical and clinical specific features of cancer cachectic patients.

Bacterial mobilization and transport through manure enriched soils: Experiment and modeling.

A precise evaluation of bacteria transport and mathematical investigations are useful for best management practices in agroecosystems. In this study, using laboratory experiments and modeling approaches, we assess the transport of bacteria released from three types of manure (cow, sheep, and poultry) to find the importance of the common manures in agricultural activities in soil and water pollution. Thirty six intact soil columns with different textures (sandy, loamy, and silty clay loam) were sampled. Fecal coliform leaching from layers of the manures on the soil surface was conducted under steady-state saturated flow conditions at 20 °C for up to four Pore Volumes (PVs). Separate leaching experiments were conducted to obtain the initial concentrations of bacteria released from the manures (Co). Influent (Co) and effluent (C) bacteria concentrations were measured by the plate-count method and the normalized concentrations (C/C0) were plotted versus PV representing the breakthrough curves (BTCs). Transport parameters were predicted using the attachment/detachment model (two-kinetic site) in HYDRUS-1D. Simulations fitted well the experimental data (R2 = 0.50-0.96). The attachment, detachment, and straining coefficients of bacteria were more influenced by the soils treated with cow manure compared to the sheep and poultry manures. Influent curves of fecal coliforms from the manures (leached without soil) illustrated that the poultry manure had the highest potential to pollute the effluent water from the soils in term of concentration, but the BTCs and simulated data related to the treated soils illustrated that the physical shape of cow manure was more important to both straining and detachment of bacteria back into the soil solution. Detachment trends of bacteria were observed through loam and silty clay loam soils treated with cow manure compared to the cow manure enriched sandy soil. We conclude that management strategies must specifically minimize the effect of fecal coliform concentrations before field application, especially for the combination of poultry and cow manures, which has higher solubility and tailing behavior, respectively. Interestingly, the addition of sheep manure with all three soils had the lowest mobilization of bacteria. We also suggest studying the chemistry of soil solution affected by manures to present all relevant information which affect bacterial movement through soils during leaching.

Predictive mathematical models of cancer signalling pathways.

Complex intracellular signalling networks integrate extracellular signals and convert them into cellular responses. In cancer cells, the tightly regulated and fine-tuned dynamics of information processing in signalling networks is altered, leading to uncontrolled cell proliferation, survival and migration. Systems biology combines mathematical modelling with comprehensive, quantitative, time-resolved data and is most advanced in addressing dynamic properties of intracellular signalling networks. Here, we introduce different modelling approaches and their application to medical systems biology, focusing on the identifiability of parameters in ordinary differential equation models and their importance in network modelling to predict cellular decisions. Two related examples are given, which include processing of ligand-encoded information and dual feedback regulation in erythropoietin (Epo) receptor signalling. Finally, we review the current understanding of how systems biology could foster the development of new treatment strategies in the context of lung cancer and anaemia.

Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood.

MOTIVATION: Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model parameters are determined by the amount and quality of experimental data. This knowledge is essential for further investigation of model predictions. For this reason a major topic in modeling is identifiability analysis. RESULTS: We suggest an approach that exploits the profile likelihood. It enables to detect structural non-identifiabilities, which manifest in functionally related model parameters. Furthermore, practical non-identifiabilities are detected, that might arise due to limited amount and quality of experimental data. Last but not least confidence intervals can be derived. The results are easy to interpret and can be used for experimental planning and for model reduction. AVAILABILITY: An implementation is freely available for MATLAB and the PottersWheel modeling toolbox at http://web.me.com/andreas.raue/profile/software.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Self-assembled hybrid organic-MoS3-nanoparticle catalyst for light energy conversion.

We present photocatalytically active, stable polymer-amorphous-MoS3-nanoparticle hybrid structures in aqueous solution. Below 10 nm MoS3 particles in the polymer exhibit an up to 7.5-fold increased photocatalytic activity compared to the neat nanoparticles without any additional photosensitizer. Supramolecular interactions are key in directing the structure formation of the hybrid assembly. The hybrid structures bear potential as novel affordable photocatalysts for solar energy conversion.

Regulatory demands on data quality for the environmental risk assessment of pharmaceuticals.

The evaluation of the quality of data and their use within the review of environmental risk assessment of human as well as veterinary pharmaceuticals is described from a regulatory point of view. A definition and differentiation in three categories for the reliability of data are given. Existing criteria relating to international testing standards for categorising reliability are adopted for their use within the environmental risk assessment of pharmaceuticals. A systematic documentation of evaluating reliability for literature data as well as for experimental studies (effect and environmental fate studies) is proposed. The data quality criteria are defined in order to increase the transparency of the evaluation process in Germany and thus the quality of the environmental risk assessment of pharmaceuticals.

Short-term exposure to the organotin compound triphenyltin modulates esterified steroid levels in females of Marisa cornuarietis.

Long-term exposures to organotin compounds have shown alterations on endogenous steroid levels in gastropods together with the development of imposex. However, information regarding short-term effects of these compounds on the endocrine system of gastropods is lacking. This work aimed at investigating those responses in the ramshorn snail Marisa cornuarietis by looking at both endogenous levels of free and esterified steroids and the metabolism of the androgen precursor androstenedione by digestive gland/gonad microsomal fractions. One-week exposure to the organotin compound triphenyltin (TPT) led to a significant increase in esterified testosterone (60-85%) and a decrease in esterified estradiol (50-84%) in females, but had no effect on males. The observed alterations in esterified steroids were not directly related to changes in P450 aromatase activity that remained unchanged in exposed females. The enzymes involved in the metabolism of the androgen precursor androstenedione, namely 17beta-hydroxysteroid dehydrogenases and 5alpha-reductases, were not significantly altered by TPT exposure, suggesting that such enzymes are not primary targets of TPT in M. cornuarietis. Additional studies are needed to fully understand the significance of the observed alterations in females and their potential relationship with the development of imposex.

Ordered nanopore arrays with large interpore distances via one-step anodization.

Preparation of pre-patterned alumina substrates using bottom-up techniques compatible with nanotechnology applications is still a challenge. We present a novel methodology to achieve superior order in 'anodic' alumina with large interpore distances by a convenient one-step anodization process. The use of transparent insulators renders such anodic layers applicable as templates for nanostructured photovoltaic or photoelectrochemical devices.

Adenosine(5') oligophospho-(5') guanosines and guanosine(5') oligophospho-(5') guanosines in human platelets.

We isolated and identified nucleoside(5') oligophospho-(5') nucleosides containing adenosine and guanosine (ApnG; n = 3-6) as well as diguanosine polyphosphates (GpnG; n = 3-6) in human platelets. For identification, UV spectrometry, matrix-assisted laser desorption/ionization, postsource decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic cleavage experiments were used. The adenosine(5') oligophospho-(5') guanosines act as vasoconstrictors and growth factors. The diguanosine polyphosphates are potent modulators of growth in vascular smooth muscle cells, but do not affect vascular tone.

The effect of organotin compounds on gender specific androstenedione metabolism in the freshwater ramshorn snail Marisa cornuarietis.

In a recent study, we demonstrated that androstenedione was mainly converted to testosterone (T) and 5alpha-dihydrotestosterone (DHT) by digestive gland/gonad complex microsomal fractions isolated from male Marisa cornuarietis, whereas it was primarily metabolized to 5alpha-dihydroandrostenedione (DHA) by females. In the present work, the sexual dimorphic metabolism of androstenedione was further investigated, and attributed to a higher 17beta-hydroxysteroid dehydrogenase activity in males than in females. Thereafter, the hypothesis was tested that the metabolism of androstenedione might be affected by exposure to tributyltin (TBT) and triphenyltin (TPT), which are known to induce the development of imposex in several gastropod species. The in vitro metabolism of androstenedione, particularly the formation of DHA and DHT, was inhibited by both compounds. However, in vivo experiments showed no significant alteration in the metabolism of androstenedione in males, but a marginal (TBT) and a significant (TPT) inhibition of the formation of DHA in females exposed for 150 days to concentrations that had significantly induced the development of imposex. The ratio DHT+T/DHA, a possible indicator of metabolic androgenization, tended to increase (0.43 versus 0.35, p=0.06) in TPT exposed females. However, this ratio never reached values comparable to those found in males (11+/-1).

The tissue renin-angiotensin systems in cardiovascular disease.

The renin-angiotensin system, in its classic definition, is known as an endocrine system that exerts its actions through the effector peptide, angiotensin II, in various organs to act as a vasoconstrictor and a regulator of salt and volume homeostasis. The availability of more sensitive methods to study the biochemistry and pharmacology as well as the molecular biology of the RAS has expanded our knowledge of the system and provided new perspectives of autocrine and paracrine functions of the RAS in cardiovascular regulation. One of the more exciting of these recently described actions is the possible involvement of the RAS in the adaptive processes related to cardiovascular hypertrophy and angiogenesis.

Preoperative Serum Bilirubin and Lactate Levels Predict Postoperative Morbidity and Mortality in Liver Surgery: A Single-Center Evaluation.

BACKGROUND AND AIMS: In spite of huge developments in liver surgery during the last decades, morbidity and mortality continue to pose problems in this field. The aim of this study was to identify preoperative predictors for postoperative mortality and morbidity in liver surgery. MATERIAL AND METHODS: In a single-center study, an extensive analysis of a prospective database, including clinical criteria and laboratory tests of patients undergoing liver surgery between July 2007 and July 2012 was performed. Cutoff values of selected laboratory tests were calculated. RESULTS: In all, 337 patients were included in the study. Univariate analysis showed a statistically significant association of preoperative bilirubin, lactate, hemoglobin levels, platelet count, and prothrombin time with postoperative morbidity and mortality. Multivariate analysis revealed preoperatively elevated serum bilirubin and lactate levels as independent predictors for increased postoperative morbidity and mortality after liver surgery. CONCLUSIONS: The identified laboratory values showed a statistically significant association with postoperative morbidity and mortality in liver surgery and might be helpful in preoperative patient selection.

Bispecific antibody releasing-mesenchymal stromal cell machinery for retargeting T cells towards acute myeloid leukemia blasts.

Bispecific antibodies (bsAbs) engaging T cells are emerging as a promising immunotherapeutic tool for the treatment of hematologic malignancies. Because their low molecular mass, bsAbs have short half-lives. To achieve clinical responses, they have to be infused into patients continously, for a long period of time. As a valid alternative we examined the use of mesenchymal stromal cells (MSCs) as autonomous cellular machines for the constant production of a recently described, fully humanized anti-CD33-anti-CD3 bsAb, which is capable of redirecting human T cells against CD33-expressing leukemic cells. The immortalized human MSC line SCP-1 was genetically modified into expressing bsAb at sufficient amounts to redirect T cells efficiently against CD33 presenting target cells, both in vitro and in an immunodeficient mouse model. Moreover, T cells of patients suffering from acute myeloid leukemia (AML) in blast crisis eliminated autologous leukemic cells in the presence of the bsAb secreting MSCs over time. The immune response against AML cells could be enhanced further by providing T cells an additional co-stimulus via the CD137-CD137 ligand axis through CD137L expression on MSCs. This study demonstrates that MSCs have the potential to be used as cellular production machines for bsAb-based tumor immunotherapy in the future.

Influence of an elevated nutrition risk score (NRS) on survival in patients following gastrectomy for gastric cancer.

In the last years, the impact of weight loss in patients with malignant tumors has come more and more into the focus of clinical research, as the occurrence of weight loss is often associated with a reduced survival. Weight loss can be a hint for metastases in patients suffering from malignant tumors; furthermore, these patients are usually not able to be treated with chemotherapy. The aim of the study was to show the influence of weight loss and an elevated nutrition risk score on survival following tumor resection in patients suffering from gastric cancer. In 99 patients in whom a gastrectomy due to gastric cancer was performed, the nutrition risk score was calculated and its influence on mortality, morbidity and survival was analyzed. Of the included patients, 45 % of the patients gave a history of weight loss; they had significantly more often a NRS ≥ 3. In UICC stage 1a/b, a NRS ≥ 3 was associated with a significantly reduced survival compared to patients with a NRS < 3. In early tumor stages (UICC 1a/b), a NRS ≥ 3 was associated with a significantly reduced survival, while in progressed tumor stage, the influence of a poor NRS was not significant. This seems to show that in progressed stages in patients with gastric cancer, the influence of a reduced NRS is negligible.

Differential gene expression of renin and angiotensinogen in the TGR(mREN-2)27 transgenic rat.

Transgenic rats carrying the murine Ren-2 gene represent a monogenetic model of hypertension characterized by low plasma renin and high extrarenal expression of the transgene. The hypothesis has been raised that stimulated local reninangiotensin systems may be responsible for the development of hypertension in this model. This study analyzes the effects of the converting enzyme inhibitor lisinopril, which specifically interferes with the renin-angiotensin system, and the direct vasodilator dihydralazine on the renal and extrarenal expression of renin and angiotensinogen. A comparison of gene expression between heterozygous and homozygous transgenic and normal Sprague-Dawley rats was also performed. We demonstrate high sensitivity of blood pressure toward converting enzyme inhibition in transgenic TGR(mREN-2)27 rats. In the kidney, expression of the transgene and the endogenous renin gene increased, suggesting that both are modulated by lisinopril in a similar manner. On the other hand, blood pressure reduction by dihydralazine did not abolish renal renin suppression in transgenic rats, indicating that mechanisms different from direct effects of blood pressure account for renin suppression. Homozygosity for the transgene led to increased Ren-2 expression and higher blood pressure and had opposite effects on angiotensinogen expression compared with heterozygous rats. Cardiac hypertrophy was reduced by lisinopril but not dihydralazine and was positively correlated with cardiac angiotensinogen expression. Increased angiotensin II in the adrenal gland of TGR(mREN-2)27 rats, which overexpresses the transgene, provides evidence that this leads to enhanced generation of tissue angiotensin II. We conclude that expression of the mouse transgene, the endogenous rat renin gene, and the angiotensinogen gene is subject to differential tissue-specific regulation. Reversal of cardiovascular damage with the converting enzyme inhibitor but not dihydralazine suggests that angiotensin II generated locally may be involved in the pathogenesis of hypertension and structural changes in TGR(mREN-2)27 rats.