Numerical determination of the material properties of porous dust cakes

The formation of planetesimals requires the growth of dust particles through collisions. Micron-sized particles must grow by many orders of magnitude in mass. In order to understand and model the processes during this growth, the mechanical properties, and the interaction cross sections of aggregates with surrounding gas must be well understood. Recent advances in experimental (laboratory) studies now provide the background for pushing numerical aggregate models onto a new level. We present the calibration of a previously tested model of aggregate dynamics. We use plastic deformation of surface asperities as the physical model to bring critical velocities for sticking into accordance with experimental results. The modified code is then used to compute compression strength and the velocity of sound in the aggregate at different densities. We compare these predictions with experimental results and conclude that the new code is capable of studying the properties of small aggregates.Comment: Accepted for publication in A&

Compression Behaviour of Porous Dust Agglomerates

The early planetesimal growth proceeds through a sequence of sticking collisions of dust agglomerates. Very uncertain is still the relative velocity regime in which growth rather than destruction can take place. The outcome of a collision depends on the bulk properties of the porous dust agglomerates. Continuum models of dust agglomerates require a set of material parameters that are often difficult to obtain from laboratory experiments. Here, we aim at determining those parameters from ab-initio molecular dynamics simulations. Our goal is to improveon the existing model that describe the interaction of individual monomers. We use a molecular dynamics approach featuring a detailed micro-physical model of the interaction of spherical grains. The model includes normal forces, rolling, twisting and sliding between the dust grains. We present a new treatment of wall-particle interaction that allows us to perform customized simulations that directly correspond to laboratory experiments. We find that the existing interaction model by Dominik & Tielens leads to a too soft compressive strength behavior for uni and omni-directional compression. Upon making the rolling and sliding coefficients stiffer we find excellent agreement in both cases. Additionally, we find that the compressive strength curve depends on the velocity with which the sample is compressed. The modified interaction strengths between two individual dust grains will lead to a different behaviour of the whole dust agglomerate. This will influences the sticking probabilities and hence the growth of planetesimals. The new parameter set might possibly lead to an enhanced sticking as more energy can be stored in the system before breakup.Comment: 11 pages, 14 figures, accepted for publication in A&

Respiratory Syncytial Virus Infection in Patients with Hematological Diseases: Single-Center Study and Review of the Literature

Background.Respiratory syncytial virus (RSV) causes significant mortality in patients with hematological diseases, but diagnosis and treatment are uncertain. Methods.We retrospectively identified RSV-infected patients with upper or lower respiratory tract infection (RTI) by culture, antigen testing, and polymerase chain reaction from November 2002 through April 2007. Patients with severe immunodeficiency (SID; defined as transplantation in the previous 6 months, T or B cell depletion in the previous 3 months, graft-versus-host disease [grade, ⩾2], leukopenia, lymphopenia, or hypogammaglobulinemia) preferentially received oral ribavirin, intravenous immunoglobulin, and palivizumab. The remaining patients with moderate immunodeficiency (MID) preferentially received ribavirin and intravenous im munoglobulin. Results.We identified 34 patients, 22 of whom had upper RTI (10 patients with MID and 12 with SID) and 12 of whom had lower RTI (2 with MID and 10 with SID). Thirty-one patients were tested by polymerase chain reaction (100% of these patients had positive results; median RSV load, 5.46 log10 copies/mL), 30 were tested by culture (57% had positive results), and 25 were tested by antigen testing (40% had positive results). RSV-attributed mortality was 18% (6 patients died) and was associated with having ⩾2 SID factors (P=.04), lower RTI (P=.01), and preengraftment (P=.012). Among 12 patients with MID (7 of whom received treatment), no progression or death occurred. Nine patients with SID and upper RTI received treatment (7 patients received ribavirin, intravenous immunoglobulin, and palivizumab); infection progressed to the lower respiratory tract in 2 patients, and 1 patient died. Ten patients with SID and lower RTI were treated, 5 of whom died, including 4 of 6 patients who received ribavirin, intravenous immunoglobulin, and palivizumab. The duration of RSV shedding correlated with the duration of symptoms in patients with SID but exceeded symptom duration in patients with MID (P<.05). Conclusions.Lower RTI, ⩾2 SID criteria, and preengraftment are risk factors for RSV-attributed mortality. Polymerase chain reaction may optimize diagnosis and monitoring. Oral ribavirin therapy seems safe, but trials are needed to demonstrate its efficac

Integrated planning guidance material for example UWCS development

Where to be in 2050? How to facilitate change towards sustainable urban water service? Policy makers are challenged with rising and emerging change pressures on traditional urban water management practices and infrastructures. Changing social, economic and environmental patterns will affect the urban water services of tomorrow - the backbone of our society. This guide centres the urban water management transitions framework by Brown et al. 2009 characterising the evolution and the example future UWCS development. Furthermore, this guide provides information and assistance for shaping the transition towards the described, desirable urban water futures by addressing visioning, lock-in effects, tools to measure the current state of sustainability, principles of resilience, flexibility and adaptivity in terms of urban water systems and the five dimensions of UWCS sustainability regarding future pressures and trends about, among others, climate change, population growth and changing water demand.Nottarp-Heim, D.; Merkel, W.; Alegre, H.; Gormley, A.; Hein, A.; Alegre (2015). Integrated planning guidance material for example UWCS development. http://hdl.handle.net/10251/4745

External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study

Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of 30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS-independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT

Numerical Simulations of Highly Porous Dust Aggregates in the Low-Velocity Collision Regime

A highly favoured mechanism of planetesimal formation is collisional growth. Single dust grains, which follow gas flows in the protoplanetary disc, hit each other, stick due to van der Waals forces and form fluffy aggregates up to centimetre size. The mechanism of further growth is unclear since the outcome of aggregate collisions in the relevant velocity and size regime cannot be investigated in the laboratory under protoplanetary disc conditions. Realistic statistics of the result of dust aggregate collisions beyond decimetre size is missing for a deeper understanding of planetary growth. Joining experimental and numerical efforts we want to calibrate and validate a computer program that is capable of a correct simulation of the macroscopic behaviour of highly porous dust aggregates. After testing its numerical limitations thoroughly we will check the program especially for a realistic reproduction of various benchmark experiments. We adopt the smooth particle hydrodynamics (SPH) numerical scheme with extensions for the simulation of solid bodies and a modified version of the Sirono porosity model. Experimentally measured macroscopic material properties of silica dust are implemented. We calibrate and test for the compressive strength relation and the bulk modulus. SPH has already proven to be a suitable tool to simulate collisions at rather high velocities. In this work we demonstrate that its area of application can not only be extended to low-velocity experiments and collisions. It can also be used to simulate the behaviour of highly porous objects in this velocity regime to a very high accuracy.The result of the calibration process in this work is an SPH code that can be utilised to investigate the collisional outcome of porous dust in the low-velocity regime.Comment: accepted by Astronomy & Astrophysic

The Degree of t-System Remodeling Predicts Negative Force-Frequency Relationship and Prolonged Relaxation Time in Failing Human Myocardium

The normally positive cardiac force-frequency relationship (FFR) becomes flat or negative in chronic heart failure (HF). Here we explored if remodeling of the cardiomyocyte transverse tubular system (t-system) is associated with alterations in FFR and contractile kinetics in failing human myocardium. Left-ventricular myocardial slices from 13 failing human hearts were mounted into a biomimetic culture setup. Maximum twitch force (F), 90% contraction duration (CD90), time to peak force (TTP) and time to relaxation (TTR) were determined at 37 degrees C and 0.2-2 Hz pacing frequency. F-1(Hz)/F-0.(5)(Hz) and F-2(Hz)/F-0.(5)(Hz) served as measures of FFR, intracellular cardiomyocyte t-tubule distance (Delta TT) as measure of t-system remodeling. Protein levels of SERCA2, NCX1, and PLB were quantified by immunoblotting. F-1(Hz)/F-0.(5)(Hz) (R-2 = 0.82) and F-2(Hz)/F-0.(5)(Hz) (R-2 = 0.5) correlated negatively with Delta TT, i.e., samples with severe t-system loss exhibited a negative FFR and reduced myocardial wall tension at high pacing rates. PLB levels also predicted F-1(Hz)/F-0.(5)(Hz), but to a lesser degree (R-2 = 0.49), whereas NCX1 was not correlated (R-2 = 0.02). CD90 correlated positively with Delta TT (R-2 = 0.39) and negatively with SERCA2/PLB (R-2 = 0.42), indicating that both the t-system and SERCA activity are important for contraction kinetics. Surprisingly, Delta TT was not associated with TTP (R-2 = 0) but rather with TTR (R-2 = 0.5). This became even more pronounced when interaction with NCX1 expression was added to the model (R-2 = 0.79), suggesting that t-system loss impairs myocardial relaxation especially when NCX1 expression is low. The degree of t-system remodeling predicts FFR inversion and contraction slowing in failing human myocardium. Moreover, together with NCX, the t-system may be important for myocardial relaxation

Aplastic anemia and concomitant autoimmune diseases

The association of aplastic anemia (AA) with other autoimmune diseases (AID) has been described but so far not systematically evaluated. We assessed the incidence and the outcome of concomitant AID in a retrospective, single-center study of 243 patients with severe AA treated between 1974 and 2006 with either immunosuppression (186) or hematopoietic stem cell transplantation (57) and a median follow-up time of 9.3years (0-33). Clinically manifest AID were observed in 24 out of 243 (10 ± 3.7%) patients. Age at diagnosis of AA was significantly younger in patients without AID compared to patients with AID (median, 20 versus 52years; P < 0.001). In 12 patients where the diagnosis of AID was done before AA therapy, response to antithymocyte globulin was good for AA (ten out of 12) but not for AID (2 out of 12). In 13 patients in which AID occurred after first-line therapy, the median time to the AID was 7years (range 3months-27.5years

Mocravimod, a Selective Sphingosine-1-Phosphate Receptor Modulator, in Allogeneic Hematopoietic Stem Cell Transplantation for Malignancy

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option for patients with acute myelogenous leukemia. Outcomes are limited by leukemia relapse, graft-versus-host disease (GVHD), and abnormal immune reconstitution. Mocravimod (KRP203) is an oral sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod retains T cell effector function, a main differentiator to immunosuppressants. In preclinical models, mocravimod improves survival by maintaining graft-versus-leukemia (GVL) activity while reducing GVHD. In patients undergoing allo-HSCT for hematological malignancies, mocravimod is postulated to prevent GVHD by redistributing allogeneic donor T cells to lymphoid tissues while allowing a sufficient GVL effect in the lymphoid, where malignant cells usually reside. The primary objective of this study was to assess the safety and tolerability of mocravimod in patients undergoing allo-HSCT for hematologic malignancies. Secondary objectives were to determine the pharmacokinetic profiles of mocravimod and its active metabolite mocravimod-phosphate in this patient group, as well as to assess GVHD-free, relapse free survival at 6 months after the last treatment. In this 2-part, single- and 2-arm randomized, open-label trial, we evaluated the safety, tolerability, and pharmacokinetics of mocravimod in allo-HSCT recipients (ClinicalTrials.gov identifier NCT01830010). Patients received either 1 mg or 3 mg mocravimod per day on top of standard of care GVHD prophylaxis with either cyclosporine A/methotrexate or tacrolimus/methotrexate. We found that mocravimod can be safely added to standard treatment regimens in patients with hematologic malignancies requiring allo-HSCT. Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplantation outcomes. Our results indicate that mocravimod is safe and support a larger study to investigate its efficacy in a homogeneous acute myelogenous leukemia patient population undergoing allo-HSCT