Cooperative phagocytosis underlies macrophage immunotherapy of solid tumours and initiates a broad anti-tumour IgG response

Macrophages are abundant in solid tumours and typically associate with poor prognosis, but macrophage clusters in tumour nests have also been reported as beneficial even though dispersed macrophages would have more contacts with cancer cells. Here, by maximizing both phagocytic activity and macrophage numbers, we discover cooperative phagocytosis by low entropy clusters in rapidly growing engineered immuno-tumouroids. The results fit the calculus of proliferation-versus-engulfment, and rheological measurements and molecular perturbations provide a basis for understanding phagocytic disruption of a tumour's cohesive forces in soft cellular phases. The perturbations underscore the utility of suppressing a macrophage checkpoint in combination with an otherwise ineffective tumour-opsonizing monoclonal antibody, and the approach translates in vivo to tumour elimination that durably protects mice from re-challenge and metastasis. Adoptive transfer of engineered macrophages increases the fraction of mice that eliminate tumours and potentially overcomes checkpoint blockade challenges in solid tumours like insufficient permeation of blocking antibodies and on-target, off-tumour binding. Finally, anti-cancer IgG induced in vivo are tumour-specific but multi-epitope and contribute to a phagocytic feedback that drives macrophage clustering in vitro. Given that solid tumours remain challenging for immunotherapies, durable anti-tumour responses here illustrate unexpected advantages in maximizing net phagocytic activity.

Hyperconcentrated Mucus Unifies Submucosal Gland and Superficial Airway Dysfunction in Cystic Fibrosis

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway CF model revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Utilizing proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, proteomics analyses of CF sputum revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and within SMGs of the CF lung.

The Need to Accurately Define and Measure the Properties of Particles

When dealing with powders, a fundamental knowledge of their physical parameters is indispensable, with different methods and approaches proposed in literature. Results obtained differ widely and it is important to define standards to be applied, both toward the methods of investigation and the interpretation of experimental results. The present research intends to propose such standards, while defining general rules to be respected. Firstly, the problem of defining the particle size is inspected. It was found that describing the size of a particle is not as straightforward as one might suspect. Factors of non-sphericity and size distributions make it impossible to put ‘size’ in just one number. Whereas sieving can be used for coarser particles of a size in excess of about 50 µm, instrumental techniques span a wide size range. For fine particles, the occurrence of cohesive forces needs to be overcome and solvents, dispersants and sample mixing need to be applied. Secondly, the shape of the particles is examined. By defining sphericity, irregularly shaped particles are described. Finally, the density of particles, of particle assemblies and their voidage (volume fraction of voids) and the different ways to investigate them are explored.

THE CONCEPT OF WIND AND DUST IN THE QUR’ĀN; A Study of Surah Ibrahim (14):18

The article explains of one verses from the verse of amtal, namely Ibrahim verse 18 which discusses the interpretation of the tafsir scholars who explain the action committed by infidels and the ashes that are dust by strong winds when the wind blowns. The related example is the dust which blown by the wind because the dust turns out to be nothing and you will not be able to do anything if you are faced with strong winds in the high wind season, surely the dust will fly everywhere chaotically and will not be able to return to original place. Besides that, the dust that is contained in the Qur’ān is flying dust, where the flying dust has a negative impact and unbenefit to human health and the environment. This fact provides a very broad discourse enrichment, that the wind can occur if one day there is air pressure in the horizontal direction, there will be a movement of air mass transfer from a place with high air pressure to a place with low air pressure. Dust particles are known as small numbers of particles that are lifted up by the force of wind stress. The value of the wind stress force in this event is expressed by the fluid or threshold. This threshold depends not only on the properties of the fluid, but also on the gravity and cohesive forces between the particles which oppose the lift force of the fluid

Fifth fundamental force and unification of fundamental forces

There are four known fundamental forces of nature and there is a need to combine them into a unified theory. Progress has been made toward this goal but gravity remains an issue. However, the four forces are body forces that act on points. They together do not make the universe a closed system. Here, I identify a surface force, which acts outward normal to the surface of the universe. Further, using water drop hanging in a vacuum as a model, I provide a formula to find the magnitude of this force. The fifth force is generated by surface tension, a property of dark energy. On the other hand, matter particles interact with each other through cohesive forces and with dark matter through adhesive forces. I give a range of functional forms of all cohesive and adhesive forces and present an equation that unifies all the forces of nature.

Probing regolith-covered surfaces in low gravity

The surfaces of many planetary bodies, including asteroids, moons, and planets, are composed of rubble-like grains held together by varying levels of gravitational attraction and cohesive forces. Future instrumentation for operation on, and interacting with, such surfaces will require efficient and effective design principles and methods of testing. Here we present results from the EMPANADA experiment (Ejecta-Minimizing Protocols for Applications Needing Anchoring or Digging on Asteroids) which flew on several reduced gravity parabolic flights. EMPANADA studies the effects of the insertion of a flexible probe into a granular medium as a function of ambient gravity. This is done for an idealized 2D system as well as a more realistic 3D sample. To quantify the dynamics inside the 2D granular material we employ photoelasticity to identify the grain-scale forces throughout the system, while in 3D experiments we use simulated regolith. Experiments were conducted at three different levels of gravity: martian, lunar, and microgravity. In this work, we demonstrate that the photoelastic technique provides results that complement traditional load cell measurements in the 2D sample, and show that the idealized system exhibits similar behaviour to the more realistic 3D sample. We note that the presence of discrete, stick-slip failure events depends on the gravitational acceleration.

MATERIALI CON BAGNABILITÀ CONTROLLATA. UN’ISPIRAZIONE DALLA NATURA

The wettability of solid surfaces is the result of the balance between adhesive and cohesive forces. When adhesive forces at the solid/liquid interface prevail over the cohesive forces in the liquid, the drops will spread over the solid leading to a good wetting as in the case of water over an hydrophilic surface. When instead the adhesive forces are weak, the liquid will not wet the surface remaining in droplets, as water on a polymer. Natural materials exhibit tailored wetting behavior: for instance, certain leaves and insects present superhydrophobic properties. By mimicking what nature creates in an exemplary way, the wetting properties of systems can be tailored experimentally to obtain materials with great applicative impact. The possible applications of such phenomena are very numerous and span from biomaterials to antistain materials, from antifog surfaces to systems for the protection of cultural heritage.

Fragmentation or Coherence? Does International Dispute Settlement Achieve Comprehensive Justice?

The debate about whether international law is fragmented or coherent is no arid discussion. If fragmentation is in the ascendancy, many commentators argue that something needs to be done. It is, of course, vital for the success of any legal system to achieve some level of predictability and certainty and to consistently deliver comprehensive justice. A legal system must, first and foremost, be a justice system, if there is any point to its existence. If it is not, then there may be another debate about whether it may be called a ‘legal’ system or a ‘justice’ system at all. I will review the debate between various leading commentators and analyse their proposals. My review of a number of different aspects and areas of international law shows that although fragmentation is apparent, the level of coherence in international law is far more surprising than fragmentation, which is inevitable, just as it is in the development of national law in, say, a federal polity. Just when international law seems to be fragmented somewhere, coherence is being achieved elsewhere. The result may be characterised as a kind of ‘equilibrium’ in which antagonistic and cohesive forces in international law keep one another in check, somehow balancing the other out. International law is capable of delivering comprehensive justice even if, at times, it may seem unlikely or elusive.

Regimes of Memory in the Context of Autocratic Breakthroughs

Global climate change, migration waves, Brexit, Trump’s presidency, the politics of Putin’s Russia, the narrow-minded technocratic executive leadership of the EU, and the constitutional crisis in Spain, present old, reborn, and new challenges to the integrative and cohesive forces of the diversity and openness of Europe. The current autocratic breakthroughs in Hungary and Poland are part of these phenomena. This introductory article focuses on the common preconditions of autocratic breakthroughs, especially on the uncertainties, anxieties and fears rooted in unprocessed traumatic experiences. They have created the possibility of pitting the case of the community against the case of liberty, producing powder-kegs of political hysteria in which the political language of national egotism and regimes of memory strongly connect with each other.