Regulatory T-cells in chronic graft-versus-host disease following extracorporeal photopheresis: correlation with skin and global organ responses, and ability to taper steroids

Background: Induction of immune tolerance by an increase in regulatory T (Treg) cells after extracorporeal photopheresis (ECP) is thought to contribute to how ECP exerts its therapeutic effect in patients with chronic graft-versus-host disease (cGvHD). We investigated whether percentages and absolute counts of Treg cells changed post-ECP, and examined correlation with response. Methods: Absolute counts and % of CD4+ T cells and Treg cells (CD4 + CD25 + FOXP3 + CD127dim/-) were evaluated using flow cytometry in 32 patients with cGvHD treated by ECP for a minimum of 3 months, and up to 12 months. CD4+ or Treg cells at baseline to 12 months post-ECP were compared with changes in skin disease scores or global organ involvement, or the ability to taper steroids, at 14, 28, and 56 weeks. Results: Regulatory T cells % increased significantly above any overall changes in CD4+ % at 6, 9, and 12 months post-ECP. There was no statistically significant association between Treg cells and skin or steroid response, whereas a larger increase in CD4+ count from baseline to 1 to 3 months corresponded to increased odds of being able to reduce steroid dose by 50% or greater at 14 weeks. Skin and global organ responders at 28 weeks had higher median Treg cell counts 3 months post-ECP than nonresponders, as did steroid responders at 56 weeks who were 12 months post-ECP. Conclusions: Regulatory T cell counts and % varied greatly among cGvHD patients, and the increase post-ECP was not significant until 6 months. No clear correlation was found between Treg cells and clinical improvement, suggesting that increases in Treg cell numbers and/or proportions are not driving the mechanism leading to a response after ECP

Short-time scaling behavior of growing interfaces

The short-time evolution of a growing interface is studied within the framework of the dynamic renormalization group approach for the Kadar-Parisi-Zhang (KPZ) equation and for an idealized continuum model of molecular beam epitaxy (MBE). The scaling behavior of response and correlation functions is reminiscent of the ``initial slip'' behavior found in purely dissipative critical relaxation (model A) and critical relaxation with conserved order parameter (model B), respectively. Unlike model A the initial slip exponent for the KPZ equation can be expressed by the dynamical exponent z. In 1+1 dimensions, for which z is known exactly, the analytical theory for the KPZ equation is confirmed by a Monte-Carlo simulation of a simple ballistic deposition model. In 2+1 dimensions z is estimated from the short-time evolution of the correlation function.Comment: 27 pages LaTeX with epsf style, 4 figures in eps format, submitted to Phys. Rev.

Quasi Stable Black Holes at the Large Hadron Collider

We adress the production of black holes at LHC and their time evolution in space times with compactified space like extra dimensions. It is shown that black holes with life times of hundred fm/c can be produced at LHC. The possibility of quasi-stable remnants is discussed.Comment: 4 pages, 3 figures, typos removed, omitted factors included, accepted for publicatio

Understanding the Spatial Clustering of Severe Acute Respiratory Syndrome (SARS) in Hong Kong

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated

Bulk dynamics for interfacial growth models

We study the influence of the bulk dynamics of a growing cluster of particles on the properties of its interface. First, we define a {\it general bulk growth model} by means of a continuum Master equation for the evolution of the bulk density field. This general model just considers arbitrary addition of particles (though it can be easily generalized to consider substraction) with no other physical restriction. The corresponding Langevin equation for this bulk density field is derived where the influence of the bulk dynamics is explicitly shown. Finally, when it is assumed a well-defined interface for the growing cluster, the Langevin equation for the height field of this interface for some particular bulk dynamics is written. In particular, we obtain the celebrated Kardar-Parisi-Zhang (KPZ) equation. A Monte Carlo simulation illustrates the theoretical results.Comment: 6 pages, 2 figure

Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development

Malaria is one of the most dangerous infectious diseases due to its high infection and mortality rates, especially in the tropical belt. Plasmodium falciparum (P. falciparum), the most virulent malaria parasite in humans, was recently reported to develop resistance against the final efficient antimalarial drug, artemisinin. Little is known about the resistance mechanisms, which further complicates the problem as a proper counteraction is unable to be taken. Hence, the understanding of drug mode of action and its molecular target is valuable knowledge that needs to be considered to develop the next generation of antimalarial drugs. P. falciparum protein kinase (Pf PK) is an attractive target for antimalarial chemotherapy due to its vital roles in all P. falciparum life stages. Moreover, overall structural differences and the presence of unique Pf PKs that are absent in human kinome, suggesting specific inhibition of Pf PK without affecting human cells is achievable. To date, at least 86 eukaryotic protein kinases have been identified in P. falciparum kinome, by which less than 40 were validated as potential targets at the erythrocytes stage. In this review, recent progress of the furthest validated Pf PKs; Pf Nek-1, Pf CDPK1, Pf CDPK4, Pf PKG, and Pf CLK-3 will be briefly discussed. © 2020, Malaysian Society for Parasitology. All rights reserved

Non-Linear Stochastic Equations with Calculable Steady States

We consider generalizations of the Kardar--Parisi--Zhang equation that accomodate spatial anisotropies and the coupled evolution of several fields, and focus on their symmetries and non-perturbative properties. In particular, we derive generalized fluctuation--dissipation conditions on the form of the (non-linear) equations for the realization of a Gaussian probability density of the fields in the steady state. For the amorphous growth of a single height field in one dimension we give a general class of equations with exactly calculable (Gaussian and more complicated) steady states. In two dimensions, we show that any anisotropic system evolves on long time and length scales either to the usual isotropic strong coupling regime or to a linear-like fixed point associated with a hidden symmetry. Similar results are derived for textural growth equations that couple the height field with additional order parameters which fluctuate on the growing surface. In this context, we propose phenomenological equations for the growth of a crystalline material, where the height field interacts with lattice distortions, and identify two special cases that obtain Gaussian steady states. In the first case compression modes influence growth and are advected by height fluctuations, while in the second case it is the density of dislocations that couples with the height.Comment: 9 pages, revtex

Markers of cardiac dysfunction in cognitive impairment and dementia

Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD). We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia. A case–control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale. We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64–49.79) and dementia (OR: 16.89; 95%CI: 2.02–142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23–48.58). These associations were independent of other vascular risk factors. In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD

Phenomenology of Randall-Sundrum Black Holes

We explore the phenomenology of microscopic black holes in the $S^1/Z_2$ Randall-Sundrum (RS) model. We consider the canonical framework in which both gauge and matter fields are confined to the brane and only gravity spills into the extra dimension. The model is characterized by two parameters, the mass of the first massive graviton $(m_1)$, and the curvature $1/\ell$ of the RS anti-de Sitter space. We compute the sensitivity of present and future cosmic ray experiments to various regions of $\ell$ and $m_1,$ and compare with that of Runs I and II at the Tevatron. As part of our phenomenological analysis, we examine constraints placed on $\ell$ by AdS/CFT considerations.Comment: Version to appear in Physical Review D; contains additional analysis on sensitivity of OW

Warp propagation in astrophysical discs

Astrophysical discs are often warped, that is, their orbital planes change with radius. This occurs whenever there is a non-axisymmetric force acting on the disc, for example the Lense-Thirring precession induced by a misaligned spinning black hole, or the gravitational pull of a misaligned companion. Such misalignments appear to be generic in astrophysics. The wide range of systems that can harbour warped discs - protostars, X-ray binaries, tidal disruption events, quasars and others - allows for a rich variety in the disc's response. Here we review the basic physics of warped discs and its implications.Comment: To be published in Astrophysical Black Holes by Haardt et al., Lecture Notes in Physics, Springer 2015. 19 pages, 2 figure