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Computational modeling of the melt pool dynamics in laser-based powder bed fusion metal additive manufacturing (PBF-LB/M) promises to shed light on fundamental mechanisms of defect generation. These processes are accompanied by rapid evaporation so that the evaporation-induced recoil pressure and cooling arise as major driving forces for fluid dynamics and temperature evolution. The magnitude of these interface fluxes depends exponentially on the melt pool surface temperature, which, therefore, has to be predicted with high accuracy. The present work utilizes a diffuse interface finite element model based on a continuum surface flux (CSF) description of interface fluxes to study dimensionally reduced thermal two-phase problems representative for PBF-LB/M in a finite element framework. It is demonstrated that the extreme temperature gradients combined with the high ratios of material properties between metal and ambient gas lead to significant errors in the interface temperatures and fluxes when classical CSF approaches, along with typical interface thicknesses and discretizations, are applied. It is expected that this finding is also relevant for other types of diffuse interface PBF-LB/M melt pool models. A novel parameter-scaled CSF approach is proposed, which is constructed to yield a smoother temperature field in the diffuse interface region, significantly increasing the solution accuracy. The interface thickness required to predict the temperature field with a given level of accuracy is less restrictive by at least one order of magnitude for the proposed parameter-scaled approach compared to classical CSF, drastically reducing computational costs. Finally, we showcase the general applicability of the parameter-scaled CSF to a 3D simulation of stationary laser melting of PBF-LB/M considering the fully coupled thermo-hydrodynamic multi-phase problem, including phase change.

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Accurate measurement of core temperature is of utmost importance during on-pump cardiac surgery, for detection of hypothermia before cardiopulmonary bypass (CPB), guidance of temperature management on CPB, active rewarming on CPB and guidance of warming therapy after CPB. Most temperature measurement methods are known to become inaccurate during rapid changes in core temperature and suffer from delayed detection of temperature changes. Zero-heat-flux temperature (ZHF) measurement from the lateral forehead may be an alternative, non-invasive method quantifying the core temperature. A prospective, observational, multicentre study was conducted in one hundred patients scheduled for on-pump coronary artery bypass grafting. Core temperatures were measured every minute by two zero-heat-flux thermometer (SpotOn™) and a bladder thermometer and a pulmonary artery catheter (PAC) in the period after induction of anesthesia until CPB. Accuracy and precision of both methods were compared against core temperature measured in the pulmonary artery using the method of Bland and Altman. A high accuracy (around 0.1 °C) and a very good precision (Limits of agreement (LoA) - 0.6; 0.4 °C) were found between zero-heat-flux thermometer and core temperature measured by PAC. Among the two ZHF thermometers the bias was negligible (- 0.003 °C) with narrow LoA of - 0.42 °C and 0.41 °C. In contrast, bias between bladder temperature and PAC temperature was large (0.51 °C) with corresponding LoA of - 0.06 °C and 1.1 °C. ZHF thermometers are in contrast to bladder temperature a reliable core temperature monitor in cardiac surgery during the period after induction of anestesia until CPB. The zero-heat-flux method can provide clinicians reliably with continuous and non-invasive measurements of core temperature in normothermic and mild hypothermic temperature ranges and therefore can be helpful to guide temperature management.

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In this study, simultaneous positron emission tomography (PET)/magnetic resonance (MR) imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-d-glucose (18F-FDG), 11C-choline, and 18F-fluorothymidine (18F-FLT) to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.

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Persistent infections with human papillomavirus type 16 (HPV16), HPV18, or HPV31 are necessary for the development of cervical cancer, implying that HPVs have evolved immunoevasive mechanisms. Recent global transcriptome analyses indicated that these HPV types downregulate the constitutive expression of interferon (IFN)-stimulated genes (ISGs), but the underlying mechanism is not well understood. Comparative analyses of ISG transcription in keratinocytes with complete HPV16, -18, and -31 genomes revealed that antiviral genes (IFIT1 and MX1), genes involved in IFN signaling (STAT1), proapoptotic genes (TRAIL and XAF1), and pathogen recognition receptors (TLR3, RIG-I, and MDA5) are inhibited to similar extents by HPV16, -18, and -31. The lower expression of pathogen receptors in HPV-positive cells correlated with a greatly impaired induction of IFN-ß and also of IFN-λ1, -2, and -3 upon receptor stimulation. IFN-κ is constitutively expressed in normal keratinocytes and is strongly repressed by HPV16, -18, and -31. ISGs downregulated in HPV-positive cells can be reactivated by IFN-κ expression. The viral E6 and E7 oncogenes are sufficient for IFN-κ repression, with E6 being mainly responsible. E6 inhibits IFN-κ transcription independently from binding to PDZ proteins. IFN-κ expression can be activated in only one cell line by E6AP knockdown but can be activated in all tested HPV-positive cells by addition of a DNA methyltransferase inhibitor, suggesting that HPVs modulate DNA methylation. Taken together, these results suggest that carcinogenic HPVs target IFN-κ by different pathways in keratinocytes to inhibit both antiviral ISGs and pathogen recognition receptors, which in turn reduces the expression of inducible IFNs.

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