I'm Infected, Eat Me! Innate Immunity Mediated by Live, Infected Cells Signaling To Be Phagocytosed

Innate immunity against pathogens is known to be mediated by barriers to pathogen invasion, activation of complement, recruitment of immune cells, immune cell phagocytosis of pathogens, death of infected cells, and activation of the adaptive immunity via antigen presentation. Here, we propose and review evidence for a novel mode of innate immunity whereby live, infected host cells induce phagocytes to phagocytose the infected cell, thereby potentially reducing infection. We discuss evidence that host cells, infected by virus, bacteria, or other intracellular pathogens (i) release nucleotides and chemokines as find-me signals, (ii) expose on their surface phosphatidylserine and calreticulin as eat-me signals, (iii) release and bind opsonins to induce phagocytosis, and (iv) downregulate don’t-eat-me signals CD47, major histocompatibility complex class I (MHC1), and sialic acid. As long as the pathogens of the host cell are destroyed within the phagocyte, then infection can be curtailed; if antigens from the pathogens are cross-presented by the phagocyte, then an adaptive response would also be induced. Phagocytosis of live infected cells may thereby mediate innate immunity

The impact incentive types on organisational performance in anglo cultures: a reply to Drake, Haka and Ravenscroft (1999)

Experimental research suffers from biases introduced by experiment design choices, such as the choice of alternative incentive and reward structures. We propose that framing rewards in a broader typology when researchers make decision about which reward structures to use in an experiment will minimise the potential for a false choice bias. To highlight this problem we replicate Drake, Haka and Ravenscrofts (1999) incentive structure experiment using a simpler, more theory driven design. Drake et al (1999) propose that organisational performance maybe be better if group compensation is given in preference to individualistic compensation, within the context of an information rich environment (using activity based costing). In particular, Drake et al (1999) apply an experimental research design to test that proposition using U.S. MBA students. Their results suggest that, ceteris paribus, given a group in preference to an individualistic incentive scheme, innovation, efficiency and profitability may improve. We argue that this conclusion is inconsistent with the incentive structure choices faced by managers, the societal values of the U.S., culture and agency theories in general. A possible explanation for Drake et als (1999) result is the use of a tournament incentive scheme as the basis for individual compensation. As such, we replicate the Drake et al (1999) experiment using Australian university students and an individual profit incentive scheme as the basis for individual compensation. Our results, in contrast to Drake et al. (1999), indicate that given an individual in preference to group incentive scheme, task performance improves in an information rich environment. This experiment highlights the false choice bias that reduces the generalizability of experimental research in general and highlights the value of propositions couched in a broader reward typology

Gravity and elevation changes at Askja, Iceland

Ground tilt measurements demonstrate that Askja is in a state of unrest, and that in the period 1988 - 1991 a maximum 48 +/- 3 µrad tilt occurred down towards the centre of the caldera. This is consistent with 126 mm of deflation at the centre of the caldera with a 2.5 - 3.0 km depth to the source of deformation. The volume of the subsidence bowl is 6.2 x 106 m3. When combined with high precision microgravity measurements, the overall change in sub-surface mass may be quantified. After correction for the observed elevation change using the free air gradient of gravity measured for each station, the total change in mass is estimated to be less than 109 kg. A small residual ground inflation and net gravity increase in the eastern part of the caldera may be caused by dyke intrusion in this region. The minimum dimensions of such an intrusion or complex of intrusions are 1m width, up to 100m deep and up to several hundred metres thick

In vitro and In vivo Characterisation of Piroxicam-Loaded Dika Wax Lipospheres

Purpose: To formulate piroxicam-loaded lipospheres and evaluate their in vitro and in vivo properties.Method: Piroxicam-loaded lipospheres were prepared by hot  homogenization technique using dika wax and Phospholipon® 90G (1:1, 1:2 and 2:1) as the lipid matrix. Characterisation, based on particle sizeand morphology, pH, drug content and encapsulation efficiency, were carried out on the lipospheres. In vitro release was evaluated in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties of the piroxicam-loaded lipospheres were studied using healthy, adult Wistar rats.Result: Photomicrographs revealed spherical particles in the range of 1.66 – 3.56 ìm. The results also indicated that lipospheres formulated with lipid matrix 1:1 and containing 0.25 % piroxicam had the highest encapsulation efficiency of 84 %. In vitro release data showed that lipospheres formulated with lipid matrix having higher concentration of dika wax exhibited the fastest drug release of drug with maximum release time between 60 - 70 min. The lipospheres exhibited good anti-inflammatoryproperties with 58.6 % oedema inhibition at 5 h. Piroxicam-loaded liposheres had an ulcer index of zero while, the reference (plain piroxicam) had an ulcer index of 15.00 ± 1.23 (p < 0.05).Conclusion: Piroxicam lipospheres formulated with a mixture of dika wax and phospholipid exhibited good in vitro and in vivo properties.Keywords: Dika wax, Lipospheres, Piroxicam, Phospholipid, Ulcerogenicity, Anti-inflammator

Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis

Muscle dysfunction is a common feature of severe sepsis and multi-organ failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP-3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit ROS production. Using a murine model, we examined metabolic, cardiovascular and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3(-/-) mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Mitochondrial membrane potential was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP-3 protein abundance at 24 hours, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3(-/-) mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and phosphorylation pathway. However, UCP-3 does not play an important functional role, despite its upregulation

On Closing the Circle

Ghirardi sought to “close the circle”—to find a place for human experience of measurement outcomes within quantum mechanics. I argue that Ghirardi’s spontaneous collapse approach succeeds at this task, and in fact does so even without the postulation of a particular account of “primitive ontology”, such as a mass density distribution or a discrete “flashes”. Nevertheless, I suggest that there is a remaining ontological problem facing spontaneous collapse theories concerning the use of classical concepts like “particle” in quantum mechanical explanation at the micro-level. Neither the mass density nor the flash ontology is any help with this problem

General Form of the Color Potential Produced by Color Charges of the Quark

Constant electric charge $e$ satisfies the continuity equation $\partial_\mu j^{\mu}(x)= 0$ where $j^\mu(x)$ is the current density of the electron. However, the Yang-Mills color current density $j^{\mu a}(x)$ of the quark satisfies the equation $D_\mu[A] j^{\mu a}(x)= 0$ which is not a continuity equation ($\partial_\mu j^{\mu a}(x)\neq 0$) which implies that a color charge $q^a(t)$ of the quark is not constant but it is time dependent where $a=1,2,...8$ are color indices. In this paper we derive general form of color potential produced by color charges of the quark. We find that the general form of the color potential produced by the color charges of the quark at rest is given by \Phi^a(x) =A_0^a(t,{\bf x}) =\frac{q^b(t-\frac{r}{c})}{r}\[\frac{{\rm exp}[g\int dr \frac{Q(t-\frac{r}{c})}{r}] -1}{g \int dr \frac{Q(t-\frac{r}{c})}{r}}\]_{ab} where $dr$ integration is an indefinite integration, ~~ $Q_{ab}(\tau_0)=f^{abd}q^d(\tau_0)$, ~~$r=|{\vec x}-{\vec X}(\tau_0)|$, ~~$\tau_0=t-\frac{r}{c}$ is the retarded time, ~~$c$ is the speed of light, ~~${\vec X}(\tau_0)$ is the position of the quark at the retarded time and the repeated color indices $b,d$(=1,2,...8) are summed. For constant color charge $q^a$ we reproduce the Coulomb-like potential $\Phi^a(x)=\frac{q^a}{r}$ which is consistent with the Maxwell theory where constant electric charge $e$ produces the Coulomb potential $\Phi(x)=\frac{e}{r}$.Comment: Final version, two more sections added, 45 pages latex, accepted for publication in JHE

The mixed problem for the Laplacian in Lipschitz domains

We consider the mixed boundary value problem or Zaremba's problem for the Laplacian in a bounded Lipschitz domain in R^n. We specify Dirichlet data on part of the boundary and Neumann data on the remainder of the boundary. We assume that the boundary between the sets where we specify Dirichlet and Neumann data is a Lipschitz surface. We require that the Neumann data is in L^p and the Dirichlet data is in the Sobolev space of functions having one derivative in L^p for some p near 1. Under these conditions, there is a unique solution to the mixed problem with the non-tangential maximal function of the gradient of the solution in L^p of the boundary. We also obtain results with data from Hardy spaces when p=1.Comment: Version 5 includes a correction to one step of the main proof. Since the paper appeared long ago, this submission includes the complete paper, followed by a short section that gives the correction to one step in the proo