Localized wave structures: Solitons and beyond.

The review is concerned with solitary waves and other localized structures in the systems described by a variety of generalizations of the Korteweg-de Vries (KdV) equation. Among the topics we focus upon are "radiating solitons," the generic structures made of soliton-like pulses, and oscillating tails. We also review the properties of solitary waves in the generalized KdV equations with the modular and "sublinear" nonlinearities. Such equations have an interesting class of solutions, called compactons, solitary waves defined on a finite spatial interval. Both the properties of single solitons and the interactions between them are discussed. We show that even minor non-elastic effects in the soliton-soliton collisions can accumulate and result in a qualitatively different asymptotic behavior. A statistical description of soliton ensembles ("soliton gas"), which emerges as a major theme, has been discussed for several models. We briefly outline the recent progress in studies of ring solitons and lumps within the framework of the cylindrical KdV equation and its two-dimensional extension. Ring solitons and lumps (2D solitons) are of particular interest since they have many features in common with classical solitons and yet are qualitatively different. Particular attention is paid to interactions between the objects of different geometries, such as the interaction of ring solitons and shear flows, ring solitons and lumps, and lumps and line solitons. We conclude our review with views of the future developments of the selected lines of studies of localized wave structures in the theory of weakly nonlinear, weakly dispersive waves.

Outcomes of diagnosed COVID-19 cancer patients: concerning results of a systematic review.

Since the outbreak of coronavirus disease 2019 (COVID-19), malignancy was shown to be prevalent in COVID-19 patients. This systematic review's searches were conducted in MEDLINE(R), Embase, Web of Science, and Scopos. Considered for inclusion were all reports on outcomes of cancer patients diagnosed with COVID-19. A total of 1099 references were identified through database searching and manual search. Finally, 17 references comprising 88 cancer patients, diagnosed with COVID-19, were included. Prevalence of cancer patients with COVID-19 was shown to range from 0.9% to 3%. The evidence suggested a severe clinical course of 50.6% in COVID-19 diagnosed cancer patients and a mortality rate of 34.5%. Subgroup analysis according to recent anti-cancer treatment showed a similar pattern, with the most concerning results in patients receiving recent immunotherapy/immunosuppressive treatment. COVID-19 morbidity and mortality among cancer patients should be reduced by consideration of testing asymptomatic COVID-19 cancer patients, reduction of hospital visits, and consideration of anti-cancer treatment.

On heating of tissues by shear waves generated by ultrasound.

An additional heating caused by the shear wave generated by an ultrasonic wave incident on a soft tissue boundary is considered for different tissue parameters and wave frequencies in the MHz range. The shear wave structure and the space-time dynamics of the temperature field are studied for three realistic examples of tissue parameters. It is shown that in viscous tissues the shear component can significantly contribute to the heating in a narrow layer near the boundary.

Self-synchronization in an ensemble of nonlinear oscillators.

The paper describes the results of study of a system of coupled nonlinear, Duffing-type oscillators, from the viewpoint of their self-synchronization, i.e., generation of a coherent field (order parameter) via instability of an incoherent (random-phase) initial state. We consider both the cases of dissipative coupling (e.g., via the joint radiation) and reactive coupling in a Hamiltonian system.

Beyond the KdV: Post-explosion development.

Several threads of the last 25 years' developments in nonlinear wave theory that stem from the classical Korteweg-de Vries (KdV) equation are surveyed. The focus is on various generalizations of the KdV equation which include higher-order nonlinearity, large-scale dispersion, and a non-local integral dispersion. We also discuss how relatively simple models can capture strongly nonlinear dynamics and how various modifications of the KdV equation lead to qualitatively new, non-trivial solutions and regimes of evolution observable in the laboratory and in nature. As the main physical example, we choose internal gravity waves in the ocean for which all these models are applicable and have genuine importance. We also briefly outline the authors' view of the future development of the chosen lines of nonlinear wave theory.

Radiation force in nonlinear, focused beams.

The effect of cumulative nonlinear distortions in a focused ultrasonic wave on the dissipative radiation force (RF) is analyzed using a simplified analytical model separating the stages of geometrical focusing and the subsequent diffraction in the focal area. It is shown that in the absence of shocks, nonlinear steepening can significantly amplify the RF as compared with a harmonic wave. Two different types of dissipation, one corresponding to a classical viscous fluid and another typical of many biological tissues, are considered.

Internal solitons in laboratory experiments: comparison with theoretical models.

Nonlinear internal solitary waves observed in laboratory experiments are discussed from the standpoint of their relation to different soliton theories, from the classical integrable models such as the Korteweg-de Vries, Gardner, Benjamin-Ono, and Joseph-Kubota-Ko-Dobbs equations and their modifications, through the nonintegrable models describing higher-order nonlinear effects, viscosity, rotation, and cylindrical spreading, to the strongly nonlinear models. First, these theoretical models are briefly described and, then, laboratory data and their comparison with the theory are presented.

Perturbation theory for kinks and its application for multisoliton interactions in hydrodynamics.

Using an integrable Gardner equation as an example, a perturbation theory is developed for systems in which limiting-amplitude solitons exist in the form of a pair of distanced kinks. Approximate equations describing multisoliton interactions are derived and further used for modeling the evolution of an arbitrary set of solitons. The results are compared with an exact solution and numerical results. The theory is applied to data from observation of a train of strongly nonlinear internal waves in the ocean.

Nonlinear wave interactions in bubble layers.

Due to the large compressibility of gas bubbles, layers of a bubbly liquid surrounded by pure liquid exhibit many resonances that can give rise to a strongly nonlinear behavior even for relatively low-level excitation. In an earlier paper [Druzhinin et al., J. Acoust. Soc. Am. 100, 3570 (1996)] it was pointed out that, by exciting the bubbly layer in correspondence of two resonant modes, so chosen that the difference frequency also corresponds to a resonant mode, it might be possible to achieve an efficient parametric generation of a low-frequency signal. The earlier work made use of a simplified model for the bubbly liquid that ignored the dissipation and dispersion introduced by the bubbles. Here a more realistic description of the bubble behavior is used to study the nonlinear oscillations of a bubble layer under both single- and dual-frequency excitation. It is found that a difference-frequency power of the order of 1% can be generated with incident pressure amplitudes of the order of 50 kPa or so. It appears that similar phenomena would occur in other systems, such as porous waterlike or rubberlike media.

Application of three-dimensional resonant acoustic spectroscopy method to rock and building materials.

This paper presents the experimental and theoretical results of applying resonant acoustic spectroscopy (RAS) to determine elastic parameters and losses in such consolidated granular materials as rock and building bricks. First, the theoretical aspects of the RAS method are outlined. A computer code for the rectangular and cylindrical samples was developed and tested. The results of experiments on specimens of rock and ceramic brick are then described. Finally, a modification of the previously published RUS algorithm is presented which permits a significant reduction in computing time for elongated samples.

Selective recruitment of neutrophils and lymphocytes by thrombin: a role for NF-kappaB.

With the use of a whole blood laminar flow chamber system, we examined the types of leukocytes, adhesion molecules and the role of nuclear factor-kappaB (NF-kappaB) in thrombin-induced leukocyte recruitment. Primary human umbilical vein endothelial cells (HUVEC) stimulated with thrombin induced a significant increase in P-selectin-dependent neutrophil recruitment. Unexpectedly, brief thrombin stimulation (3 min) of endothelium also induced a significant lymphocyte recruitment 4 h later in addition to neutrophil recruitment. E-selectin antibody reduced neutrophil recruitment by >90%, whereas vascular adhesion molecule-1 (VCAM-1)/alpha4-integrin were primarily responsible for lymphocyte recruitment. To examine whether NF-kappaB contributed to leukocyte recruitment 4 h post thrombin stimulation, we treated HUVEC with the NF-kappaB inhibitor MG-132 for 1 h before thrombin stimulation. MG-132 significantly reduced the number of rolling (77.1%) and adherent (79.9%) leukocytes compared with thrombin stimulation alone. The inhibitor was more effective at preventing lymphocyte than neutrophil recruitment, consistent with its greater effect on VCAM-1 versus E-selectin expression. Tumor necrosis factor-alpha- and MG-132-treated HUVEC displayed no inhibition of leukocyte recruitment despite a decrease in NF-kappaB activation. In summary, thrombin causes predominant neutrophil recruitment via rapid P-selectin expression but also a delayed E-selectin- and VCAM-1-dependent neutrophil and lymphocyte recruitment via de novo protein synthesis. Although NF-kappaB mobilization was essential for thrombin-mediated VCAM-1-dependent recruitment, it only partially contributed to E-selectin-dependent recruitment.

Functional alpha4-integrin: a newly identified pathway of neutrophil recruitment in critically ill septic patients.

Using a novel flow chamber assay system and whole blood, we show that leukocytes from septic individuals have a four-fold elevation of adhesion, but not rolling, on a P-selectin/beta2-integrin substrate. Most leukocytes from septic patients (but not healthy controls) that bound vascular cell adhesion molecule 1 (VCAM-1) were neutrophils. All adhesion was inhibited with an antibody specific for the VCAM-1 ligand alpha4-integrin. The alpha4-integrin was present on neutrophils from septic patients but not on neutrophils from patients with localized bacterial infections. The plasma milieu of septic patients was sufficient to induce neutrophils from healthy subjects to bind VCAM-1 under flow conditions. This is the first description of alpha4-integrin/VCAM-1 pathway of neutrophil recruitment in human disease. This pathway may provide a new therapeutic target to reduce inappropriate neutrophil adhesion without altering the normal yet critical beta2-integrin-mediated adhesive function of neutrophils.

Translational inhibition of E-selectin expression stimulates P-selectin-dependent neutrophil recruitment.

Although known for its role in hemostasis, there is a growing body of evidence that thrombin can induce leukocyte recruitment and contribute to the inflammatory response. An in vitro parallel-plate flow chamber was used to systematically examine thrombin-induced neutrophil interactions with human endothelium. Stimulation of endothelial cells with thrombin (1 U/ml) resulted in an immediate, P-selectin-dependent increase in neutrophil rolling and adhesion that was comparable in magnitude to optimal levels of histamine (the classical inducer of P-selectin). However, thrombin, but not histamine, induced a delayed (4 h) E-selectin-dependent rolling similar to that of tumor necrosis factor-alpha, suggesting that thrombin has the unique ability to recruit neutrophils by an early P-selectin and a delayed E-selectin pathway. Surprisingly, inhibition of E-selectin expression with the general protein synthesis inhibitor cycloheximide induced P-selectin expression 4 h after thrombin stimulation. Cycloheximide and thrombin (4 h) induced sufficient P-selectin-dependent rolling to recruit as many neutrophils as were recruited with 4 h of stimulation with thrombin alone. Histamine in the presence of cycloheximide or cycloheximide alone did not evoke the P-selectin response at 4 h, suggesting that this was not due to direct cycloheximide induction of P-selectin. Treatment of endothelium with tumor necrosis factor-alpha (an E-selectin inducer) and cycloheximide also eliminated E-selectin expression but, much like thrombin, induced P-selectin expression and neutrophil recruitment. In conclusion, inhibition of E-selectin via protein synthesis inhibition activates the protein synthesis-independent pathway of P-selectin expression to support adequate leukocyte recruitment.

Antithrombin and ischemia/reperfusion.

Acute inflammation, a localized response that occurs in various diseases, is characterized by neutrophil infiltration into tissues. This process requires neutrophils to initially tether and roll along the endothelium of postcapillary venules before undergoing firm adhesion and emigration out of the vasculature into the tissues. Recently, thrombin has been implicated at multiple sites in the inflammatory cascade, and may represent an important link between inflammation and thrombosis. Our recent studies demonstrate that thrombin is an important mediator of neutrophil-dependent injury in ischemia-reperfusion injury. Furthermore, antithrombin concentrate may be therapeutically efficacious in ischemia-reperfusion injury, as it is capable of attenuating the thrombin-mediated effects on neutrophil-endothelial interactions.

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NO-depleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations.

A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process.

The aim of this study was to identify the molecular mechanisms involved in neutrophil adhesion to immobilized platelets with particular focus on the possible existence of a juxtacrine system for neutrophil-platelet interactions. Platelets were immobilized onto collagen (type I)-coated coverslips that were placed in a flow chamber and neutrophils were perfused across these confluent monolayers at a shear stress of 1 to 4 dynes/cm2. Neutrophils rolled, and a significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin was expressed in very large quantities on the surface of platelets and mediated all of the rolling, whereas the beta2-integrin mediated firm adhesion. An activation mechanism for adhesion was necessary inasmuch as fixed neutrophils continued to roll on immobilized platelets, but did not adhere. Platelets adherent to collagen produced significant levels of platelet-activating factor (PAF). Accordingly, the firm adhesion of neutrophils to platelets was significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of only the platelets with acetylhydrolase, which converts membrane-associated PAF to lyso-PAF, prevented 60% of the adhesion. These data suggest that PAF, on the surface of platelets, mediated a significant portion of the adhesive interaction. Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs but not dextran sulfate) to the platelets caused rolling neutrophils to immediately adhere, an event that was not observed on histamine or thrombin-treated endothelium or P-selectin transfectants. These data support the view that a juxtacrine activation process exists on immobilized platelets for neutrophils. This process can be greatly enhanced on platelets and may involve a signaling mechanism through P-selectin.

Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell interactions.

Recently, it was reported that preconditioning reduced leukocyte adhesion following ischemia-reperfusion (I/R). We further examined the effects of preconditioning and adenosine not only on neutrophil adhesion but also on neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a decrease in neutrophil rolling velocity; a profound increase in neutrophil rolling, adhesion, and microvascular dysfunction; and a reduction in venular shear rates associated with 60 min ischemia and 60 min reperfusion in the feline mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and microvascular dysfunction but did not affect the flux of rolling neutrophils. Adenosine deaminase A1 and A2 adenosine-receptor antagonists had only minor effects on the preconditioning responses. Pretreatment of vessels with exogenous adenosine reduced neutrophil adhesion and microvascular permeability and improved neutrophil rolling velocity and shear forces associated with I/R, but the flux of rolling neutrophils was not affected. Finally, in vitro experiments revealed that adenosine had absolutely no direct effect on neutrophil-endothelial cell interactions. In conclusion, our data suggest that adenosine plays only a minor role in preconditioned vessels and that adenosine per se may not directly affect neutrophil-endothelial cell interactions.

Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion.

BACKGROUND: P-selectin has recently been shown to be essential for leukocyte rolling after the reperfusion of ischemic mesentery. However, the mediators responsible for neutrophil rolling in ischemic microvessels remain entirely unclear. METHODS AND RESULTS: Intravital microscopy was used to examine leukocyte kinetics in a feline mesentery ischemia/reperfusion model. Sixty minutes of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. Pretreatment with the endogenous antithrombotic agent antithrombin III (ATIII) infused as a bolus (250 U/kg) reduced neutrophil rolling and adhesion to preischemic levels during reperfusion. No effect was seen with heat-inactive ATIII. Importantly, ATIII posttreatment also significantly reduced neutrophil rolling and adhesion during reperfusion, suggesting that ATIII can reverse the leukocyte recruitment response induced by ischemia/reperfusion. Vascular permeability was also reduced by 50% after ATIII administration. To determine whether ATIII could reverse thrombin-induced rolling directly, neutrophil rolling was performed on human endothelium in flow chambers. Indeed, thrombin-induced rolling, but not histamine-induced rolling, could be rapidly reversed with ATIII on endothelium, suggesting that ATIII affects thrombin rather than directly affecting neutrophils or the endothelium. CONCLUSIONS: This study demonstrates for the first time that thrombin plays an important role in ischemia-induced leukocyte rolling and adhesion and that ATIII can be used therapeutically postreperfusion to attenuate the leukocyte recruitment response in inflammation without the nonspecific effects associated with anti-adhesion molecule therapy.