First-in-man evaluation of 124I-PGN650: A PET tracer for detecting phosphatidylserine as a biomarker of the solid tumor microenvironment

Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies

The tautological ring of Mg,n via Pandharipande-Pixton-Zvonkine r-spin relations

We use relations in the tautological ring of the moduli spaces Mg,n derived by Pandharipande, Pixton, and Zvonkine from the Givental formula for the r-spin Witten class in order to obtain some restrictions on the dimensions of the tautological rings of the open moduli spacesMg,n. In particular, we give a new proof for the result of Looijenga (for n = 1) and Buryak et al. (for n > 2) that dimRg-1(Mg,n) ≤ n. We also give a new proof of the result of Looijenga (for n = 1) and Ionel (for arbitrary n > 1) that Ri(Mg,n) = 0 for i > g and give some estimates for the dimension of Ri(Mg,n) for i ≤ g - 2

Polycaprolactone Microfibrous Scaffolds to Navigate Neural Stem Cells

Fibrous scaffolds have shown promise in tissue engineering due to their ability to improve cell alignment and migration. In this paper, poly(ε-caprolactone) (PCL) fibers are fabricated in different sizes using a microfluidic platform. By using this approach, we demonstrated considerable flexibility in ability to control the size of the fibers. It was shown that the average diameter of the fibers was obtained in the range of 2.6–36.5 μm by selecting the PCL solution flow rate from 1 to 5 μL min–1 and the sheath flow rate from 20 to 400 μL min–1 in the microfluidic channel. The microfibers were used to create 3D microenvironments in order to investigate growth and differentiation of adult hippocampal stem/progenitor cells (AHPCs) in vitro. The results indicated that the 3D topography of the PCL substrates, along with chemical (extracellular matrix) guidance cues supported the adhesion, survival, and differentiation of the AHPCs. Additionally, it was found that the cell deviation angle for 44–66% of cells on different types of fibers was less than 10°. This reveals the functionality of PCL fibrous scaffolds for cell alignment important in applications such as reconnecting serious nerve injuries and guiding the direction of axon growth as well as regenerating blood vessels, tendons, and muscle tissue

The impact of responsible leadership on knowledge sharing behavior through the mediating role of person−organization fit and moderating role of higher educational institute culture

The aim of this study is to investigate the effect of responsible leadership on knowledge sharing behavior. Furthermore, we investigated the mediating role of person-organization fit in the relationship between responsible leadership and knowledge sharing behavior. Moreover, higher educational institute culture moderates the relationship between responsible leadership and person-organization fit. The data collected from 295 respondents (teachers, head of department and management staff) from universities located in different cities of China. The data were gathered at one time, and therefore, the study is cross-sectional. Because of COVID-19, there have been a few universities closed; therefore, data were also collected online. The data were analyzed quantitatively using the partial least squares (PLS)−structural equation modelling (SEM) technique. The result indicated that responsible leadership is positively and significantly influential on knowledge sharing behavior directly, and also indirectly through mediator person-organization fit. Also, the higher educational institute culture positively and significantly moderates the relationship between responsible leadership and person-organization fit

Uniaxial Tensile Properties of AS4 3D Woven Composites with Four Different Resin Systems: Experimental Results and Analysis: Property Computations

As a part of the NASA Composite Technology for Exploration project, eight different AS4 3D orthogonal woven composite panels were manufactured and were subjected to mechanical testing including uniaxial tension along the weaves' warp direction. Each set, with four different resin systems (KCR-IR6070, EP2400, RTM6, and RS-50), included weave architectures designed using 12K and 6K AS4 carbon fiber yarns. For the tension testing conducted at Room Temperature Ambient (RTA) conditions, the elastic modulus and strength of these eight panels (as-processed and thermally-cycled) were measured and compared while the potential evolution of micro-cracking before and after thermal cycling were monitored via optical microscopy and X-Ray Computed Tomography. The data set also included test results of the as-processed materials at Elevated Temperature Wet (ETW) conditions. In the second part of this study, efforts were made to compute elastic constants for AS4 6K/RTM6 and AS4 12K/RTM6 materials by implementing a finite element approach and the Multiscale Generalized Method of Cells (MSGMC) technique developed at NASA Glenn Research Center. Digimat-FE was used to model the weave architectures, assign properties, calculate yarn properties, create the finite element mesh, and compute the elastic properties by applying periodic boundary conditions to finite element models of each repeating unit cell. The required input data for MSGMC was generated using Matlab from Digimat exported weave information. Experimental and computational results were compared, and the differences and limitations in correlating to the test data were briefly discussed

High stakes and low bars: How international recognition shapes the conduct of civil wars

When rebel groups engage incumbent governments in war for control of the state, questions of international recognition arise. International recognition determines which combatants can draw on state assets, receive overt military aid, and borrow as sovereigns—all of which can have profound consequences for the military balance during civil war. How do third-party states and international organizations determine whom to treat as a state's official government during civil war? Data from the sixty-one center-seeking wars initiated from 1945 to 2014 indicate that military victory is not a prerequisite for recognition. Instead, states generally rely on a simple test: control of the capital city. Seizing the capital does not foreshadow military victory. Civil wars often continue for many years after rebels take control and receive recognition. While geopolitical and economic motives outweigh the capital control test in a small number of important cases, combatants appear to anticipate that holding the capital will be sufficient for recognition. This expectation generates perverse incentives. In effect, the international community rewards combatants for capturing or holding, by any means necessary, an area with high concentrations of critical infrastructure and civilians. In the majority of cases where rebels contest the capital, more than half of its infrastructure is damaged or the majority of civilians are displaced (or both), likely fueling long-term state weakness

Combined spectroscopy and intensity interferometry to determine the distances of the blue supergiants P Cygni and Rigel

In this paper, we report on the spatial intensity interferometry measurements within the H$\alpha$ line on two stars: the Luminous Blue Variable (LBV) supergiant \PCygni\,and the late-type B supergiant Rigel. The experimental setup has been upgraded to allow simultaneous measurement of two polarization channels and the zero baseline correlation function. Combined with simultaneous spectra measurements and based on radiative transfer models calculated with the code CMFGEN, we were able to fit our measured visibility curves to extract the stellar distances. Our distance determinations for both \PCygni\ (1.61 $\pm$ 0.18 kpc) and Rigel (0.26 $\pm$ 0.02 kpc) agree very well with the values provided by astrometry with the Gaia and Hipparcos missions, respectively. This is the first successful step towards extending the application of the Wind Momentum Luminosity Relation method for distance calibration from an LBV supergiant to a more normal late-type B supergiant

Early subretinal allograft rejection is characterized by innate immune activity

Successful subretinal transplantation is limited by considerable early graft loss, despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a non-immunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation and the neutrophil chemoattractant, KC/GRO/CINC, was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, non-immunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7 and 28 days post-operatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b & F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ε) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p<0.001) reduced between post-operative day (POD) 3 (90% ± 4%) and POD 7 (20% ± 7%). CD11b+, F4/80+ and Gr1 Ly-6G+ cells increased significantly (p<0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Co-labeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7 and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ε was low and did not differ significantly between time-points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal for the first time a critical role for innate immune mechanisms early in subretinal graft rejection. The future success of subretinal transplantation will require more emphasis on techniques to limit innate immune-mediated graft loss, rather than focusing exclusively on suppression of the adaptive immune response