Numerical study of the hydrodynamic drag force in atomic force microscopy measurements undertaken in fluids

When atomic force microscopy (AFM) is employed for in vivo study of immersed biological samples, the fluid medium presents additional complexities, not least of which is the hydrodynamic drag force due to viscous friction of the cantilever with the liquid. This force should be considered when interpreting experimental results and any calculated material properties. In this paper, a numerical model is presented to study the influence of the drag force on experimental data obtained from AFM measurements using computational fluid dynamics (CFD) simulation. The model provides quantification of the drag force in AFM measurements of soft specimens in fluids. The numerical predictions were compared with experimental data obtained using AFM with a V-shaped cantilever fitted with a pyramidal tip. Tip velocities ranging from 1.05 to 105 µm/s were employed in water, polyethylene glycol and glycerol with the platform approaching from a distance of 6000 nm. The model was also compared with an existing analytical model. Good agreement was observed between numerical results, experiments and analytical predictions. Accurate predictions were obtained without the need for extrapolation of experimental data. In addition, the model can be employed over the range of tip geometries and velocities typically utilized in AFM measurements

Cytological features of uterine tumors resembling ovarian sex-cord tumors in liquid-based cervical cytology: a potential pitfall. Report of a unique and rare case.

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are rare uterine neoplasms of uncertain etiology that resemble the sex cord tumors of the ovary and display a combined sex cord, epithelial, and smooth muscle immunophenotype. Most tumors are associated with a benign clinical course. We report the first cytological description of uterine UTROSCTs in liquid-based cervical cytology (LBC). A menopausal woman was discovered to have a uterine intraluminal polypoid mass protruding through the vagina. A Pap test was performed, and the LBC preparation showed isolated tumor cells with scant cytoplasm and slightly irregular, ovoid nuclei with fine chromatin and small nucleoli. Final histological evaluation identified a UTROSCT. This diagnostic possibility, albeit rare, should be included in the differential diagnosis when isolated malignant-appearing adenocarcinomatous cells are seen in women in the above scenario. As these features are not specific, they may result in misinterpretation with tumors that are more common and aggressive

Informe Optoel 2021

[No abstract available

Microfluidic-based immunohistochemistry for breast cancer diagnosis: a comparative clinical study.

Breast cancer is a highly heterogeneous disease. The efficacy of tailored therapeutic strategies relies on the precise detection of diagnostic biomarkers by immunohistochemistry (IHC). Therefore, considering the increasing incidence of breast cancer cases, a concomitantly time-efficient and accurate diagnosis is clinically highly relevant. Microfluidics is a promising innovative technology in the field of tissue diagnostic, enabling for rapid, reliable, and automated immunostaining. We previously reported the microfluidic-based HER2 (human epidermal growth factor receptor 2) detection in breast carcinomas to greatly correlate with the HER2 gene amplification level. Here, we aimed to develop a panel of microfluidic-based IHC protocols for prognostic and therapeutic markers routinely assessed for breast cancer diagnosis, namely HER2, estrogen/progesterone receptor (ER/PR), and Ki67 proliferation factor. The microfluidic IHC protocol for each marker was optimized to reach high staining quality comparable to the standard procedure, while concomitantly shortening the staining time to 16 min-excluding deparaffinization and antigen retrieval step-with a turnaround time reduction up to 7 folds. Comparison of the diagnostic score on 50 formaldehyde-fixed paraffin-embedded breast tumor resections by microfluidic versus standard staining showed high concordance (overall agreement: HER2 94%, ER 95.9%, PR 93.6%, Ki67 93.7%) and strong correlation (ρ coefficient: ER 0.89, PR 0.88, Ki67 0.87; p < 0.0001) for all the analyzed markers. Importantly, HER2 genetic reflex test for all discordant cases confirmed the scores obtained by the microfluidic technique. Overall, the microfluidic-based IHC represents a clinically validated equivalent approach to the standard chromogenic staining for rapid, accurate, and automated breast cancer diagnosis

A parametric study on the dynamic response of planar multibody systems with multiple clearance joints

A general methodology for dynamic modeling and analysis of multibody systems with multiple clearance joints is presented and discussed in this paper. The joint components that constitute a real joint are modeled as colliding bodies, being their behavior influenced by geometric and physical properties of the contacting surfaces. A continuous contact force model, based on the elastic Hertz theory together with a dissipative term, is used to evaluate the intra-joint contact forces. Furthermore, the incorporation of the friction phenomenon, based on the classical Coulomb’s friction law, is also discussed. The suitable contact-impact force models are embedded into the dynamics of multibody systems methodologies. An elementary mechanical system is used to demonstrate the accuracy and efficiency of the presented approach, and to discuss the main assumptions and procedures adopted. Different test scenarios are considered with the purpose of performing a parametric study for quantifying the influence of the clearance size, input crank speed and number of clearance joints on the dynamic response of multibody systems with multiple clearance joints. Additionally, the total computation time consumed in each simulation is evaluated in order to test the computational accuracy and efficiency of the presented approach. From the main results obtained in this study, it can be drawn that clearance size and the operating conditions play a crucial role in predicting accurately the dynamic responses of multibody systems.Fundação para a Ciência e a Tecnologia (FCT

Integrated computer-aided working-fluid design and thermoeconomic ORC system optimisation

The successful commercialisation of organic Rankine cycle (ORC) systems across a range of power outputs and heat-source temperatures demands step-changes in both improved thermodynamic performance and reduced investment costs. The former can be achieved through high-performance components and optimised system architectures operating with novel working-fluids, whilst the latter requires careful component-technology selection, economies of scale, learning curves and a proper selection of materials and cycle configurations. In this context, thermoeconomic optimisation of the whole power-system should be completed aimed at maximising profitability. This paper couples the computer-aided molecular design (CAMD) of the working-fluid with ORC thermodynamic models, including recuperated and other alternative (e.g., partial evaporation or trilateral) cycles, and a thermoeconomic system assessment. The developed CAMD-ORC framework integrates an advanced molecular-based group-contribution equation of state, SAFT-γ Mie, with a thermodynamic description of the system, and is capable of simultaneously optimising the working-fluid structure, and the thermodynamic system. The advantage of the proposed CAMD-ORC methodology is that it removes subjective and pre-emptive screening criteria that would otherwise exist in conventional working-fluid selection studies. The framework is used to optimise hydrocarbon working-fluids for three different heat sources (150, 250 and 350 °C, each with mcp = 4.2 kW/K). In each case, the optimal combination of working-fluid and ORC system architecture is identified, and system investment costs are evaluated through component sizing models. It is observed that optimal working fluids that minimise the specific investment cost (SIC) are not the same as those that maximise power output. For the three heat sources the optimal working-fluids that minimise the SIC are isobutane, 2-pentene and 2-heptene, with SICs of 4.03, 2.22 and 1.84 £/W respectively

Spatial rigid-multi-body systems with lubricated spherical clearance joints : modeling and simulation

The dynamic modeling and simulation of spatial rigid-multi-body systems with lubricated spherical joints is the main purpose of the present work. This issue is of paramount importance in the analysis and design of realistic multibody mechanical systems undergoing spatial motion. When the spherical clearance joint is modeled as dry contact; i.e., when there is no lubricant between the mechanical elements which constitute the joint, a body-to-body (typically metal-to-metal) contact takes place. The joint reaction forces in this case are evaluated through a Hertzian-based contact law. A hysteretic damping factor is included in the dry contact force model to account for the energy dissipation during the contact process. The presence of a fluid lubricant avoids the direct metal-to-metal contact. In this situation, the squeeze film action, due to the relative approaching motion between the mechanical joint elements, is considered utilizing the lubrication theory associated with the spherical bearings. In both cases, the intra-joint reaction forces are evaluated as functions of the geometrical, kinematical and physical characteristics of the spherical joint. These forces are then incorporated into a standard formulation of the system’s governing equations of motion as generalized external forces. A spatial four bar mechanism that includes a spherical clearance joint is considered here as example. The computational simulations are carried out with and without the fluid lubricant, and the results are compared with those obtained when the system is modeled with perfect joints only. From the general results it is observed that the system’s performance with lubricant effect presents fewer peaks in the kinematic and dynamic outputs, when compared with those from the dry contact joint model.Fundação para a Ciência e a Tecnologia (FCT

Macrophages exert homeostatic actions in pregnancy to protect against preterm birth and fetal inflammatory injury

Macrophages are commonly thought to contribute to the pathophysiology of preterm labor by amplifying inflammation — but a protective role has not previously been considered to our knowledge. We hypothesized that given their antiinflammatory capability in early pregnancy, macrophages exert essential roles in maintenance of late gestation and that insufficient macrophages may predispose individuals to spontaneous preterm labor and adverse neonatal outcomes. Here, we showed that women with spontaneous preterm birth had reduced CD209⁺CD206⁺ expression in alternatively activated CD45⁺CD14⁺ICAM3⁻ macrophages and increased TNF expression in proinflammatory CD45⁺CD14⁺CD80⁺HLA-DR⁺ macrophages in the uterine decidua at the materno-fetal interface. In Cd11b(DTR/DTR) mice, depletion of maternal CD11b⁺ myeloid cells caused preterm birth, neonatal death, and postnatal growth impairment, accompanied by uterine cytokine and leukocyte changes indicative of a proinflammatory response, while adoptive transfer of WT macrophages prevented preterm birth and partially rescued neonatal loss. In a model of intra-amniotic inflammation–induced preterm birth, macrophages polarized in vitro to an M2 phenotype showed superior capacity over nonpolarized macrophages to reduce uterine and fetal inflammation, prevent preterm birth, and improve neonatal survival. We conclude that macrophages exert a critical homeostatic regulatory role in late gestation and are implicated as a determinant of susceptibility to spontaneous preterm birth and fetal inflammatory injury.Nardhy Gomez-Lopez, Valeria Garcia-Flores, Peck Yin Chin, Holly M. Groome, Melanie T. Bijland, Kerrilyn R. Diener, Roberto Romero, and Sarah A. Robertso

Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1, 100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM