IL -10 gene therapy for the treatment of pulmonary inflammation

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important regulatory role in inflammatory diseases. The overall goal of this research is to investigate the potential therapeutic effect of IL-10 gene therapy for the treatment of pulmonary inflammation and to develop appropriate gene delivery and expression systems for efficient gene transfer to the lung. We evaluated various liposomal and non-liposomal agents including LipofectAMINE RTM, LipofectinRTM, DOTAP, DEAE-dextran, and the DNA condensing agent protamine sulfate for their ability to promote gene transfection in macrophages. We have developed an efficient transfection protocol which is at least 20--25 fold superior to frequently used protocols for macrophage transfection. However, gene transfection in macrophages is still low. Since macrophages are known to be highly susceptible to endotoxin stimulation and endotoxin is a major contaminant of plasmid DNA preparations used in most transfection studies, we investigated the effect of endotoxin on gene transfer and the role of reactive oxygen species (ROS) in the process. Our results indicate that this decreased transfection was dependent on ROS-mediated cellular toxicity induced by endotoxin and that ·OH radicals play a major role in this process. The mechanism of anti-inflammatory action of IL-10 is incompletely understood. The present study also investigates the possible role of ROS in NF-kappaB activation and IkappaBalpha degradation and their inhibition by IL-10 in macrophages. Addition of IL-10 inhibited both IkappaBalpha degradation and generation of ·OH radicals in response to LPS stimulation. These results provide, for the first time, direct evidence for the role of IL-10 in ROS-dependent NF-kappaB activation. The next step was to develop a protocol for in vivo gene transfer. Cationic liposomes represent a class of nonviral vectors that hold great promise as gene delivery vehicles. However, recent studies have shown that they may be associated with some toxicity. We tested the hypothesis that the positive charge of liposomes is a key determinant of toxicity. ROS play a key role in cationic lipid-mediated toxicity. Finally, we established an efficient gene transfer protocol that results in clinically relevant concentrations of IL-10 protein that can downregulate mouse lung inflammation in response to LPS stimulation

Approximating the multi-level bottleneck assignment problem.

We consider the multi-level bottleneck assignment problem (MBA). This problem is described in the recent book 'Assignment Problems' by Burkard et al. (2009) on pages 188-189. One of the applications described there concerns bus driver scheduling.We view the problem as a special case of a bottleneck m-dimensional multi-index assignment problem. We give approximation algorithms and inapproximability results, depending upon the completeness of the underlying graph. Keywords: bottleneck problem; multidimensional assignment; approximation; computational complexity; efficient algorithm.Bottleneck problem; Multidimensional assignment; Approximation; Computational complexity; Efficient algorithm;

Green Hydrogen from stranded or soon to be stranded offshore oil and gas Platforms

With hydrogen being touted world over as the missing link in the renewable energy for decarbonization, the major corporations and countries around the world are beginning to embrace it, resulting in millions of dollars of investments throughout the ecosystem. An interesting trend shows a lot of traditional oil and gas companies are also pivoting their stands and parallelly investing in the hydrogen infrastructure space. The ability of hydrogen to be transported via existing pipelines either through blending with ammonia or via refurbishment of the pipelines provides additional incentives for those corporations involved in the downstream activities within the oil and gas network. This thesis gives an overview of one such scenario where possible investments can be made by the oil and gas companies to leverage their pre-existing infrastructure in order to divest, pilot and better prepare themselves for a hydrogen economy in the future. It also facilitates a way for the faster adoption of technology via investments in proven wind energy to generate green hydrogen in the offshore structures.Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminan

Thermal history of a metamorphic core complex

Fission track (FT) thermochronology studies of lower plate rocks of the Ruby Mountains-East Humbolt Range metamorphic core complex provide important constraints on the timing an nature of major middle Tertiary extension of northeast Nevada. Rocks analyzed include several varieties of mylonitic orthogneiss as well as amphibolitic orthognesses from the non-mylonitic infrastructural core. Oligocene-age porphyritic biotite granodiorite of the Harrison Pass pluton was also studied. The minerals dated include apatite, zircon, and sphene and were obtained from the same rocks that have been previously studied. FT ages are concordant and range in age from 26.4 Ma to 23.8 Ma, with all showing overlap at 1 sigma between 25.4 to 23.4 Ma. Concordancy of all FT ages from all structural levels indicates that the lower plate cooled rapidly from temperatures above approx. 285 C (assumed sphene closure temperature (2)) to below approx. 150 C (assumed apatite closure temperature) near the beginning of the Miocene. This suggests that the lower plate cooled at a rate of at least approx. 36 deg C/Ma during this event. Rapid cooling of the region is considered to reflect large-scale tectonic denudation (intracrustal thinning), the vertical complement to intense crustal extension. FT data firmly establish the upper limit on the timing of mylonitization during detachment faulting and also coincide with the age of extensive landscape disruption

Multidimensional Binary Vector Assignment problem: standard, structural and above guarantee parameterizations

In this article we focus on the parameterized complexity of the Multidimensional Binary Vector Assignment problem (called \BVA). An input of this problem is defined by $m$ disjoint sets $V^1, V^2, \dots, V^m$, each composed of $n$ binary vectors of size $p$. An output is a set of $n$ disjoint $m$-tuples of vectors, where each $m$-tuple is obtained by picking one vector from each set $V^i$. To each $m$-tuple we associate a $p$ dimensional vector by applying the bit-wise AND operation on the $m$ vectors of the tuple. The objective is to minimize the total number of zeros in these $n$ vectors. mBVA can be seen as a variant of multidimensional matching where hyperedges are implicitly locally encoded via labels attached to vertices, but was originally introduced in the context of integrated circuit manufacturing. We provide for this problem FPT algorithms and negative results ($ETH$-based results, $W$[2]-hardness and a kernel lower bound) according to several parameters: the standard parameter $k$ i.e. the total number of zeros), as well as two parameters above some guaranteed values.Comment: 16 pages, 6 figure

Facets of the axial three-index assignment polytope

We revisit the facial structure of the axial 3-index assignment polytope. After reviewing known classes of facet-defining inequalities, we present a new class of valid inequalities, and show that they are facets of this polytope. This answers a question posed by Qi and Sun~\cite{QiSun00}. Moreover, we show that we can separate these inequalities in polynomial time

Large-magnitude miocene extension in the central Mojave Desert: Implications for Paleozoic to Tertiary paleogeography and tectonics

This is the published version. Copyright 1990 American Geophysical Union. All Rights Reserved.The main Cenozoic extensional structure in the central Mojave Desert is the Waterman Hills detachment fault, which places brittlely deformed synorogenic Miocene rocks on ductilely and cataclastically deformed footwall rocks. New data are presented regarding the timing, distribution, magnitude, and significance of early Miocene extension in the area. The mylonitic fabric in the lower plate was formed at 23 Ma, based on a zircon U/Pb age from a synmylonitic intrusion. Upper plate strata consist of rhyolite flows overlain by sedimentary rocks that were apparently deposited during extensional faulting. These strata were tilted, folded, and intruded by synkinematic rhyolite plugs that are cut off at the detachment fault. Potassium metasomatism of the rhyolitic rocks is pervasive. Upper plate detrital sediment was derived from the rhyolitic rocks and from metamorphic and plutonic basement rocks not present in the area. The probable source of the exotic basement clasts is the Alvord Mountain area, presently located 35 km east-northeast of the Waterman Hills area. This source was probably much nearer to the Waterman Hills during deposition of the synorogenic deposits and has been subsequently shifted by extensional deformation. Distinctive Mesozoic plutonic rocks provide a possible tie between upper and lower plate rocks. Similar poikilitic gabbro bodies in the Goldstone area and the Iron Mountains suggest slip on the Waterman Hills detachment fault to be about 40–50 km. This is also consistent with other offset markers, such as the western edge of a Mesozoic dike swarm. When 15–20 km(?) of Tertiary extension is restored, Paleozoic eugeoclinal rocks are placed structurally above their miogeoclinal counterparts. Combined with the distribution of Triassic and Jurassic rocks, this implies post-Early Triassic and pre-Late Jurassic stacking of these lithologies