Verification of the accuracy of the SIR model in forecasting based on the improved SIR model with a constant ratio of recovery to infection rate by comparing with monitored second wave data.

The temporal evolution of second and subsequent waves of epidemics such as Covid-19 is investigated. Analytic expressions for the peak time and asymptotic behaviours, early doubling time, late half decay time, and a half-early peak law, characterizing the dynamical evolution of number of cases and fatalities, are derived, where the pandemic evolution exhibiting multiple waves is described by the semi-time SIR model. The asymmetry of the epidemic wave and its exponential tail are affected by the initial conditions, a feature that has no analogue in the all-time SIR model. Our analysis reveals that the immunity is very strongly increasing in several countries during the second Covid-19 wave. Wave-specific SIR parameters describing infection and recovery rates we find to behave in a similar fashion. Still, an apparently moderate change of their ratio can have significant consequences. As we show, the probability of an additional wave is however low in several countries due to the fraction of immune inhabitants at the end of the second wave, irrespective of the ongoing vaccination efforts. We compare with alternate approaches and data available at the time of submission. Most recent data serves to demonstrate the successful forecast and high accuracy of the SIR model in predicting the evolution of pandemic outbreaks as long as the assumption underlying our analysis, an unchanged situation of the distribution of variants of concern and the fatality fraction, do not change dramatically during a wave. With the rise of the α variant at the time of submission the second wave did not terminate in some countries, giving rise to a superposition of waves that is not treated by the present contribution.

Reconfigurable artificial microswimmers with internal feedback.

Self-propelling microparticles are often proposed as synthetic models for biological microswimmers, yet they lack the internally regulated adaptation of their biological counterparts. Conversely, adaptation can be encoded in larger-scale soft-robotic devices but remains elusive to transfer to the colloidal scale. Here, we create responsive microswimmers, powered by electro-hydrodynamic flows, which can adapt their motility via internal reconfiguration. Using sequential capillary assembly, we fabricate deterministic colloidal clusters comprising soft thermo-responsive microgels and light-absorbing particles. Light absorption induces preferential local heating and triggers the volume phase transition of the microgels, leading to an adaptation of the clusters' motility, which is orthogonal to their propulsion scheme. We rationalize this response via the coupling between self-propulsion and variations of particle shape and dielectric properties upon heating. Harnessing such coupling allows for strategies to achieve local dynamical control with simple illumination patterns, revealing exciting opportunities for developing tactic active materials.

Characterization of radical types, penetration profile and distribution pattern of the topically applied photosensitizer THPTS in porcine skin ex vivo.

The topical photodynamic therapy (PDT) is mainly used in the treatment of dermato-oncological diseases. The distribution and functionality of the photosensitizer Tetrahydroporphyrin-Tetratosylat (THPTS) was investigated using microscopic and spectroscopic methods after topical application to excised porcine skin followed by irradiation. The distribution of THPTS was determined by two-photon tomography combined with fluorescence lifetime imaging (TPT/FLIM) and confocal Raman microspectroscopy (CRM). The radicals were quantified and characterized by electron paramagnetic resonance (EPR) spectroscopy. Results show a penetration depth of THPTS into the skin down to around 12 ± 5 µm. A penetration of THPTS through the stratum corneum was not clearly observable after 1 h penetration time, but cannot be excluded. The irradiation within the phototherapeutic window (spectral range of visible and near infrared light in the range ≈ 650-850 nm) is needed to activate THPTS. An incubation time of 10 min showed the highest radical production. A longer incubation time affected the functionality of THPTS, whereby significant less radicals were detectable. During PDT mainly reactive oxygen species (ROS) and lipid oxygen species (LOS) are produced. Overall, the irradiation dose per se influences the radical types formed in skin. While ROS are always prominent at low doses, LOS increase at high doses, independent of previous skin treatment and the irradiation wavelength used.

Influence of physical-mechanical properties on SPF in sunscreen formulations on ex vivo and in vivo skin.

The sun protection factor (SPF) is related to the selected UV filters. The objective of this study was to evaluate and compare the rheological behavior and texture profile of two sunscreen formulations and to correlate these data with the obtained SPF values. Two formulations (F1 and F2) were developed with the same type and amount of UV filters - whereby one of them also contained ethoxylated lanolin as additional film former (F2). Their rheological behavior, texture profile and in vitro and in vivo SPF were analyzed. The film-forming properties were evaluated by skin profilometry and diffuse reflectance spectroscopy. The structures of the formulations were examined by two-photon tomography combined with fluorescence lifetime imaging, and the penetration profile into the stratum corneum was investigated by tape stripping. The formulation with lanolin presented lower and constant values for physical-mechanical parameters, with a higher and better reproducible SPF. Both formulations did not penetrate the viable epidermis. In conclusion, formulations with better surface deposition on the skin surface can influence the film formation and, consequently, improve the SPF. These findings are important to improve the efficacy of sunscreen formulations and reduce the addition of UV filters.

Design and construction of a simplified, gas-driven, pressure-controlled emergency ventilator.

INTRODUCTION: Due to the COVID-19 crisis or any other mass casualty situation it might be necessary to give artificial ventilation to many affected patients. Contrarily, the worldwide availability of emergency ventilators is still a shortage, especially in developing countries. METHODS: Modes of artificial ventilation were compared and the most safe, easy to use, and lung protecting principle was optimized to fit all requirements of both emergency ventilation and cost-effective mass production. RESULTS: The presented research results describe a simplified device for a pressure-controlled ventilation which works without electricity according to a known principle. Just pressurized gas and a patient connection is required. The device enables the control of basic ventilator parameters such as peak inspiratory pressure, positive end-expiratory pressure and the ventilation frequency. Further, the device is semiadaptive to the patient's lung stiffness and automatically maintains minute volume through frequency adjustment. The machine can be manufactured by turning, milling and drilling and needs purchased components with costs less than 100 USD. A sterilization and thus a reuse is possible. DISCUSSION: The presented development does not describe a ready-to-purchase ventilator, it rather outlines a refined working principle for emergency ventilation and its easiest methods of production with a minimum of requirements. The presented research aims on providing an open-source guideline for production of an emergency ventilator using worldwide available methods and thus should inspire local researchers to do a reverse engineering and eventually to put it into operation following country-specific regulations. For long-term ventilation exceeding emergency purposes, a monitoring of alarms for disconnection and violation of desired ventilator parameters should be established. The ventilator is limited to a fixed ratio between PIP and PEEP. Moreover, the ventilation frequency depends on two parameters, which needs some training. Nevertheless, the ventilator provides basic features to enable an emergency ventilation with minimal prerequisites.

Pulling-force-induced elongation and alignment effects on entanglement and knotting characteristics of linear polymers in a melt.

We employ a primitive path (PP) algorithm and the Gauss linking integral to study the degree of entanglement and knotting characteristics of linear polymer model chains in a melt under the action of a constant pulling force applied to selected chain ends. Our results for the amount of entanglement, the linking number, the average crossing number, the writhe of the chains and their PPs and the writhe of the entanglement strands all suggest a different response at the length scale of entanglement strands than that of the chains themselves and of the corresponding PPs. Our findings indicate that the chains first stretch at the level of entanglement strands and next the PP (tube) gets oriented with the "flow." These two phases of the extension and alignment of the chains coincide with two phases related to the disentanglement of the chains. Soon after the onset of external force the PPs attain a more entangled conformation, and the number of nontrivially linked end-to-end closed chains increases. Next, the chains disentangle continuously to attain an almost unentangled conformation. Using the linking matrix of the chains in the melt, we furthermore show that these phases are accompanied by a different scaling of the homogeneity of the global entanglement in the system. The homogeneity of the end-to-end closed chains first increases to a maximum and then decreases slowly to a value characterizing a completely unlinked system.

Writhe and mutual entanglement combine to give the entanglement length.

We propose a method to estimate N(e), the entanglement length, that incorporates both local and global topological characteristics of chains in a melt under equilibrium conditions. This estimate uses the writhe of the chains, the writhe of the primitive paths, and the number of kinks in the chains in a melt. An advantage of this method is that it works for both linear and ring chains, works under all periodic boundary conditions, does not require knowing the contour length of the primitive paths, and does not rely on a smooth set of data. We apply this method to linear finitely extendable nonlinear elastic chains and we observe that our estimates are consistent with those from other studies.

High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses.

Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remission in 24 patients (37%), bone marrow remission in 5 patients (8%), complete remission (with and without normalization of peripheral blood counts) in 15 patients (23%) and molecular remission with undetectable FLT3-ITD mRNA in 10 patients (15%), respectively. Seventeen of the patients without prior allo-SCT (47%) developed sorafenib resistance after a median treatment duration of 136 days (range, 56-270 days). In contrast, allo-SCT patients developed sorafenib resistance less frequently (38%) and significantly later (197 days, range 38-225 days; P=0.03). Sustained remissions were seen exclusively in the allo-SCT cohort. Thus, sorafenib monotherapy has significant activity in FLT3-ITD AML and may synergize with allogeneic immune effects to induce durable remissions.

Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: comparison of genomic and proteomic responses and anchoring to histopathological parameters.

A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplastic and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.

Ternary protein adsorption onto brushes: strong versus weak.

Attractive interactions between proteins and polyethylene glycol (PEG) give rise to ternary adsorption within PEG brushes. Experimental evidence suggests two ternary adsorption modes: (i) weak, due to nonspecific weak attraction between PEG monomers and the surface of the protein, as exemplified by serum albumin and (ii) strong, due to strong binding of PEG segments to specific protein sites as it occurs for PEG antibodies, which can involve the terminal adsorption of free chain ends or backbone adsorption due to binding to interior chain segments. Ternary adsorption affects the capacity of brushes to repress protein adsorption. The strong adsorption of antibodies can trigger an immune response that may affect the biocompatibility of the surface. Theoretical adsorption isotherms and protein concentration profiles of the three cases are compared for "parabolic" brushes, allowing for the grafting density, 1/Sigma, and degree of polymerization of the PEG chains, N, as well as the volume and surface area of the proteins. The amount of adsorbed protein per unit area, Gamma, exhibits a mode-specific maximum in all three cases. For backbone and weak adsorption, Gamma approximately N, whereas for terminal adsorption, Gamma approximately N0. In every case, the concentration profile of adsorbed proteins, ctern(z), exhibits a maximum at zmax>0 that shifts outward as Sigma decreases; zmax=0 occurs only for weak and backbone adsorption at a high Sigma value.

[Confocal laser scanning microscopy of the urothelium]. / Konfokale Laserscanningmikroskopie von Urothel.

In order to improve the detection of flat urothelial neoplasia an improvement in optical methods might be helpful. We investigated the use of confocal laser scanning microscopy in a pilot study of specimens with bladder cancer. A total of 35 fresh ex vivo specimens of 20 human bladders of patients who underwent radical cystectomy were examined with a modified confocal laser scanning microscope (670 nm). The field size was 200x200 microm and tissue was investigated up to depths of 120 microm. Resulting data sets were reconstructed three-dimensionally by computer software. Results were compared with conventional histology. Microscopically diseased bladder mucosa showed cytological and histological criteria of malignancy which were readily identifiable by laser scanning microscopy. In all cases we were able to detect the presence of malignancy with the images generated by the confocal laser scanning technique. Atypical cellular structures and subepithelial hypervascularization were prominent features. Carcinoma in situ lesions could also be identified in many cases. Confocal laser scanning microscopy allows the analysis of cellular and epithelial architecture of the urothelium in a detail which is beyond the limitations of conventional endoscopy by white light cystoscopy. Therefore, the principle would probably be of benefit if the technical limitations can be overcome.

Exact linear hydrodynamics from the Boltzmann equation.

Exact (to all orders in Knudsen number) equations of linear hydrodynamics are derived from the Boltzmann kinetic equation with the Bhatnagar-Gross-Krook collision integral. The exact hydrodynamic equations are cast in a form which allows us to immediately prove their hyperbolicity, stability, and existence of an H theorem.

From atomistic simulation to the dynamics, structure and helical network formation of dendronized polymers: the Janus chain model.

It is the purpose of this paper to establish a bottom-up multiscale approach for dendronized polymers. Based on our understanding of the phenomenology of an atomistic model for this class of polymers, we introduce a "Janus chain" (JC) model which adds a vectorial degree of freedom (Janus vector)--related to the sectorial amphiphilicity--to each segment of the linear backbone of a (classical) uncharged, semiflexible, and multibead chain representation of a polymer. The JC features induced polymeric curvature and ultimately triggers complexation. JC parameters related to the topology and chemical details are obtained from the atomistic level. Available experimental observations including the formation of superstructures and double helical conformations are well reproduced by the JC model. JC is efficiently solved via Brownian dynamics simulation and can be seen as a member of a universality class which is one (two) level(s) above the magnetic (semiflexible) chain model. It therefore should allow to model not only dendronized polymers but also structures belonging to the same class-exhibiting induced (or spontaneous) curvature--such as single stranded DNA and actin filaments.

Transplantation strategies in AML: AMLCG data.

Allogeneic stem cell transplantation (allo-SCT) is considered the most potent postremission therapy for acute myeloid leukemia (AML). Its superior antileukemic activity is largely ascribed to the powerful graft-versus-leukemia (GvL) effects exerted by donor lymphocytes. However, due to considerable treatment-related lethality the gains in relapse prevention do not necessarily translate into survival advantages in the overall patient population. Therefore, allo-SCT for adult patients with AML in first complete remission (CR1) is currently recommended only for younger and medically fit patients who are at intermediate to high risk of relapse and have an HLA-identical sibling donor. Stem cell allografting from alternative donors in CR1 is considered an option for high risk patients as defined by cytogenetic abnormalities or incomplete response after one course of induction chemotherapy and should usually be performed in the context of a clinical protocol.

Low-level viraemia of hepatitis B virus in an anti-HBc- and anti-HBs-positive blood donor.

summary In many countries, screening of hepatitis B virus (HBV) in blood donors is limited to HBsAg testing. However, if anti-HBc testing and sensitive HBV nucleic acid amplification testing (NAT) for routine screening are not prescribed, HBV viraemia might remain unrecognized. A clinically inconspicuous HBsAg-negative 35-year-old female blood donor was detected with anti-HBc antibodies following the introduction of anti-HBc screening of donors. Based on her history, she had seroconverted to anti-HBs positive (titre >7000 IU/L) after vaccination. Blood donations were routinely tested HBV-DNA negative by minipool NAT. The individual donor samples were reinvestigated by an ultrasensitive NAT with a lower detection limit of 3.8 IU/mL. Intermittent HBV viraemia was detected over a 7-year period from this donor, with a concentration ranging from 8 to 260 IU/mL. In the subsequent donor-directed lookback study, no post-transfusion hepatitis was detected. Low-level HBV viraemia in simultaneous anti-HBc- and anti-HBs-positive blood donors could only be identified with enhanced sensitivity individual polymerase chain reaction assays and is not detectable by pool HBV NAT.

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P

Thermophysical properties of gases, liquids, and solids composed of particles interacting with a short-range attractive potential.

A short-range polynomial interaction potential is introduced which has both a repulsive core and an attractive part. It is cut off smoothly such that its first and second derivatives vanish at the cutoff distance. The potential therefore enables efficient simulation studies of a model material that exhibits similarities to a full (but computationally expensive) classical Lennard-Jones system. Thermophysical properties of the model are calculated by (nonequilibrium) molecular dynamics computer simulations and compared with analytical results. Among the quantities studied is the pressure as a function of the density for various temperatures. Equations of state for the fluid and the solid are tested. The coexistence of gaseous, (metastable) liquid, and fcc solid phases is found for a range of temperatures. Bulk and shear moduli are computed. The response of the system to a shear deformation with a constant shear rate is analyzed. The liquid shows viscoelastic behavior that can be described with a Maxwell model. The solid behaves as an elastic medium up to a finite deformation and then undergoes a transition to plastic flow, which is stick-slip-like at small shear rates and continuous at higher ones.

Pressure of fluids and solids composed of particles interacting with a short-range repulsive potential

A simple short range repulsive potential (SR), with an even smoother cut off than the Weeks-Chandler-Andersen (WCA)-Lennard-Jones potential, yields practically the same pressure, both in the fluid state and for the fcc solid, when the potential parameters are chosen such that the forces are the same at the distance where the the two potential curves are equal to k(B)T. The comparison of the pressure for the SR and the WCA systems is based on molecular dynamics computer simulations. The fluid branch of the equation of state is rather well described by a modified Carnahan-Starling expression.