The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Internet of things

Manual of Digital Earth / Editors: Huadong Guo, Michael F. Goodchild, Alessandro Annoni .- Springer, 2020 .- ISBN: 978-981-32-9915-3Digital Earth was born with the aim of replicating the real world within the digital world. Many efforts have been made to observe and sense the Earth, both from space (remote sensing) and by using in situ sensors. Focusing on the latter, advances in Digital Earth have established vital bridges to exploit these sensors and their networks by taking location as a key element. The current era of connectivity envisions that everything is connected to everything. The concept of the Internet of Things(IoT)emergedasaholisticproposaltoenableanecosystemofvaried,heterogeneous networked objects and devices to speak to and interact with each other. To make the IoT ecosystem a reality, it is necessary to understand the electronic components, communication protocols, real-time analysis techniques, and the location of the objects and devices. The IoT ecosystem and the Digital Earth (DE) jointly form interrelated infrastructures for addressing today’s pressing issues and complex challenges. In this chapter, we explore the synergies and frictions in establishing an efficient and permanent collaboration between the two infrastructures, in order to adequately address multidisciplinary and increasingly complex real-world problems. Although there are still some pending issues, the identified synergies generate optimism for a true collaboration between the Internet of Things and the Digital Earth

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

The Longitudinal Relationship Between Satisfaction with Transitional Care and Social and Emotional Quality of Life Among Chronically Ill Adolescents

This study aimed to identify the relationship between satisfaction with transitional care and quality of life of chronically ill adolescents over time. This longitudinal study included adolescents with type I diabetes, juvenile idiopathic arthritis (JIA), and neuromuscular disorders (NMD). At baseline 138 respondents (response rate 31 %) filled in a questionnaire and 188 about 1 year later (response rate 43 %). Analysis of variance showed that adolescents with diabetes reported the highest physical quality of life, followed in order by those with NMD and JIA (p ≤ 0.01). Adolescents with diabetes reported the highest social quality of life, followed in order by those with JIA and NMD (both at p ≤ 0.001). Univariate analyses showed that satisfaction with transitional care at T0 was significantly related to emotional and physical quality of life at T1 (both at p ≤ 0.05). At T1, satisfaction with transitional care was significantly related to the emotional, physical, and social domains of quality of life (all at p ≤ 0.001). Multiple regression analyses revealed that satisfaction with transitional care at T1 was related to emotional (β -0.20; p ≤ 0.05) and social (β -0.35; p ≤ 0.01) quality of life domains over time. This indicates that lower gap scores, which measured differences between 'best care' and 'current care,' are associated with better social and emotional quality of life in this sample of adolescents. Satisfaction with transitional care and social and emotional quality of life are related over time

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

It's not too Late for the Harpy Eagle (Harpia harpyja): High Levels Of Genetic Diversity and Differentiation Can Fuel Conservation Programs

Article on the harpy eagle (Harpia harpyja) and how high levels of genetic diversity and differentiation can fuel conservation programs