Blood particulate analogue fluids: A review

Microfluidics has proven to be an extraordinary working platform to mimic and study blood flow phenomena and the dynamics of components of the human microcirculatory system. However, the use of real blood increases the complexity to perform these kinds of in vitro blood experiments due to diverse problems such as coagulation, sample storage, and handling problems. For this reason, interest in the development of fluids with rheological properties similar to those of real blood has grown over the last years. The inclusion of microparticles in blood analogue fluids is essential to reproduce multiphase effects taking place in a microcirculatory system, such as the cell-free layer (CFL) and Fähraeus–Lindqvist effect. In this review, we summarize the progress made in the last twenty years. Size, shape, mechanical properties, and even biological functionalities of microparticles produced/used to mimic red blood cells (RBCs) are critically exposed and analyzed. The methods developed to fabricate these RBC templates are also shown. The dynamic flow/rheology of blood particulate analogue fluids proposed in the literature (with different particle concentrations, in most of the cases, relatively low) is shown and discussed in-depth. Although there have been many advances, the development of a reliable blood particulate analogue fluid, with around 45% by volume of microparticles, continues to be a big challengeThis research was funded by the Spanish Ministry of Science and Education Grant No. PID2019-108278RB-C32 / AEI / 10.13039/501100011033, and Junta de Extremadura (Spain) Grant Nos. GR18175 and IB18005 (partially financed by FEDER funds). The authors also acknowledge the Fundação para a Ciência e a Tecnologia (FCT) for partially financing the research under the strategic grants UIDB/04077/2020, UIDB/00532/2020, and the project NORTE-01-0145-FEDER030171 (PTDC/EME-SIS/30171/2017) funded by COMPETE2020, NORTE 2020, PORTUGAL 2020, Lisb@2020, and FEDE

Hochauflösende Fourier-Transform-Infrarot-Spektroskopie der dreiatomigen Moleküle HCP, DCP und HBS

Das Molekül HCP wurde durch eine Pyrolyse von CH3PCl2 hergestellt. Die hochauflösenden FT-IR-Spektren der Knickschwingung [ny]2 und der Streckschwingungen [ny]1 und [ny]3 von HC12P und H13CP in grund- und angeregten Zuständen wurden in Absorption gemessen. Die Messungen wurden in Wellenlängenbereichen bis 3400 cm-1 mit einem Bruker IFS 120 HR Interferometer, bei verschiedenen spektralen Auflösungen bis 0.0016 cm-1, durchgeführt. Durch die Analyse der FT-IR-Spektren konnten 29 P,R-Zweige und 18 Q-Zweige für HC12P und H13CP zugeordnet werden. Für H13CP konnten 6 P,R-Zweige und 4 Q-Zweige zugeordnet werden. Zum ersten male konnte durch eine experimentelle Rotations-Vibrationsanalyse der Fermi-Resonanzpolyaden (020)/(001), (030)/(011) und (040)/(021)/(002) die entsprechenden Fermi-Resonanz-Ausserdiagonalmatrixelemente ermittelt werden. Hochauflösende FT-IR Emissionsmessungen konnten an HCP ebenfalls durchgeführt werden. Die Emissionsspektren wurden im Bereich der Knickschwingung [ny]2 aufgenommen. HCP wurde in einer Meßzelle aus Mineralquarzglas bei Temperaturen bis 1400°C synthetisiert. Die Pyrolyseprodukte wurden direkt im Reaktionsrohr gemessen. Es konnten spektroskopische Konstanten eines effektiven Hamiltonoperators für lineare Moleküle inclusive Fermi-Resonanzparametern für H12CP und H13CP ermittelt werden. Das Molekül DCP wurde durch eine Pyrolyse von CDCl2PH2 hergestellt. Aufgrund der natürlichen Häufigkeit von 13C entstand neben D12CP auch D13CP. Hochauflösende FT-IR-Spektren wurden mit einem BRUKER IFS 120 HR Fourier Transform Spektrometer aufgenommen an das eine White-Typ Meßzelle mit einer Absorptionsweglänge von 13.12 m angeschlossen war. In den Wellenlängenbereichen 400 - 600, 600 - 800, 1900 - 2700, 3300 - 4200, 4600 - 5500 und 4500 - 4900 cm-1 wurden Messungen mit Auflösungen von 0.00189, 0.00189, 0.00356, 0.0070, 0.0097 und 0.0167 cm-1 durchgeführt. Folgende Rotations-Vibrations-Bandensysteme von D12CP konnten gemessen und zugeordnet werden: die Grundschwingung [ny]2, Hotbands der [ny]2 = 1, 2, 3, 4 und der [ny]3 = 1, 2, 4, wie auch der [ny]1 = 1, 2 und verschiedene Kombinationszustände (v1v2l2v3) = 011, 110, 012, 210, 014 und 220. Eine komplette Fermi-Resonanzanalyse der folgenden Polyaden: (100)/(002), (110)/(012) und (200)/(004)/(102) konnte durchgeführt werden. Zustände der Polyaden (022)/(120) und (210)/(014)/(112) konnten nur teilweise zugeordnet werden. Die Fermi-Resonanzanalyse dieser Systeme wurde durch eine Abschätzung der Termwerte der Zustände (022) und (014) möglich. Die fundamentalen Obertonbanden der Knickschwingung von D13CP und ihrer Hotbands für [ny]2 = 1, 2 wie auch der [ny]1 Fundamentalen und [ny]3 = 2 konnten ebenfalls zugeordnet werden. Die Fermi-Resonanzanalyse von D13CP konnte vollständig für die Diade (100)/002) ausgeführt werden. Zum ersten Male wurden in dieser Arbeit folgende Bandensysteme von D12CP zugeordnet: (004) - (000), (001) - (010), (011) - (020),(011) - (001), (030) - (020), (040) - (030) und für D13CP: (010) - (000), (020) - (010), (100) - (000) and (002) - (000). Spektroskopische Konstanten inklusive Fermi-Resonanzparametern für D12CP und D13CP des effektiven Hamiltonians für lineare Moleküle werden mitgeteilt. Durch die Analyse der FT-IR-Spektren konnten 35 P,R-Zweige und 19 Q-Zweige für D12CP zugeordnet werden. Für D13CP konnten 6 P,R-Zweige und 4 Q-Zweige zugeordnet werden. Das dreiatomige Molekül HBS wurde durch eine Reaktion von Bor und Schwefel bei 1100 °C hergestellt. Die hochauflösenden FT-IR-Spektren der Streckschwingungen [ny]1 und [ny]3 von HBS und seinen Isotopomeren wurden in grund- und angeregten Rotations-Vibrationsschwingungszuständen in Absorption gemessen. Die hochauflösenden FT-IR-Spektren wurden mit einem BRUKER IFS 120 HR Fourier Transform Spektrometer in einer 40 cm langen Meßzelle aufgenommen. HBS ist ein sehr instabiles Molekül, es wurde außerhalb der Meßzelle erzeugt und durch die Meßzelle gepumt. Weiterhin wurden Infrarotmessungen von HBS mit dem Giessener Diodenlaserspektrometer (TDL) durchgeführt. Alle Linienpositionen inklusive der Kalibrationsdaten und und Plots der Übersichtsspektren werden im Anhang mitgeteilt.Samples of HCP were synthesized by pyrolysis of CH3PCl2. The High Resolution FTIR-Spectra of the bending vibration [ny]2 and the stretching vibrations [ny]1 and [ny]3 of HC12P and H13CP in ground and excitetd states have been measured in absorption. The measurements were performed in ranges up to 3400 cm-1 with a Bruker IFS 120 HR interferometer at various resolutions up to 0.0016 cm-1. Through the analysis of the spectra 29 P,R-branches and 18 Q-branches could be assigned for H12CP. For H13CP 6 P,R-branches and 4 Q-branches could also be assigned. For the first time an experimental vibrational-rotational analysis of the Fermi-resonance polyads (020)/(001), (030)/(011) and (040)/(021)/(002) could be given. The Fermi-resonance off-diagonal matrix elements for the polyads are presented. High resolution FT-IR emission mesurements of HCP were performed for the first time for HCP. Spectra were recorded in the range of the bending vibration [ny]2. HCP was synthesized and heated up to 1400 °C in a high temperature furnace. The products of the pyrolysis were directly measured in the reaction cell. Spectroscopic constants including Fermi-resonance parameters for H12CP and H13CP of the effective Hamiltonian for linear molecules are given. Samples of DCP were synthesized by pyrolysis of CDCl2PH2 (deuterodichloromethylphosphane). D13CP was present in natural abundance. High resolution FT-IR spectra were measured with a BRUKER IFS 120 HR Fourier transform spectrometer using a White-type cell with absorption path lengths up to 13.12 m. The wavenumber regions measured were 400 - 600, 600 - 800, 1900 - 2700, 3300 - 4200, 4600 - 5500 and 4500 - 4900 cm-1 with resolutions of 0.00189, 0.00189, 0.00356, 0.0070, 0.0097 and 0.0167 cm-1, respectively. In the lowest wavenumber region the [ny]2 fundamental band, hotbands from [ny]2 = 1, 2, 3, 4, and [ny]3 = 1, 2, 4 as well as n1 = 1, 2 and several combination states (v1v2l2v3) = 011, 110, 012, 210, 014 and 220 were assigned and analyzed. A complete Fermi-resonance analysis of the following polyads (100)/(002), (110)/(012) and (200)/(004)/(102) could be given. The polyads (022)/(120) and (210)/(014)/(112) were observed partially and the Fermi-resonance analysis was possible approximating one missing level for each polyad. The fundamental and overtone bands of the bending vibration of D13CP, and its hotbands from [ny]2 = 1, 2, as well as the [ny]1 fundamental and [ny]3 = 2 band were also assigned and analyzed. The Fermi-resonance analysis of D13CP, could be given for the dyad (100)/002). The bands for D12CP observed for the first time in this work are: (004) - (000), (001) - (010), (011) - (020),(011) - (001), (030) - (020), (040) - (030), and for D13CP : (010) - (000),(020) - (010), (100) - (000) and (002) - (000). Spectroscopic constants including Fermi-resonance parameters for D12CP and D13CP of the effective Hamiltonian for linear molecules are given. Through the analysis of the spectra 35 P,R-branches and 19 Q-branches could be assigned for D12CP. For D13CP 6 P,R-branches and 4 Q-branches could be assigned. Samples of HBS were synthesized by the reaction of Boron and Sulfur at 1100° C. The High Resolution FT-IR-Spectra of the stretching vibrations [ny]1 and [ny]3 of HBS and its isotopomers in ground and excitetd states have been measured in absorption. High resolution spectra were measured with a BRUKER IFS 120 HR Fourier transform spectrometer using a 40 cm long cell. HBS is an unstable molecule, it was produced outside the glastube and pumped trough the measurement aparatus. High resolution infrared measurements of HBS were also performed using the Giessen diode laser spectrometer (TDL). All line positions including the calibration data and overview plots of all spectra are given in the addendum

Ising cubes with enhanced surface couplings

Using Monte Carlo techniques, Ising cubes with ferromagnetic nearest-neighbor interactions and enhanced couplings between surface spins are studied. In particular, at the surface transition, the corner magnetization shows non-universal, coupling-dependent critical behavior in the thermodynamic limit. Results on the critical exponent of the corner magnetization are compared to previous findings on two-dimensional Ising models with three intersecting defect lines.Comment: 4 pages, 2 figures included, submitted to Phys. Rev.

Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B