Keratinocyte Growth-Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the Acute Respiratory Distress Syndrome (ARDS). In animal models of ARDS, Keratinocyte Growth Factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown.

Objectives: To test whether KGF can attenuate alveolar injury in a human model of ARDS.

Methods: Volunteers were randomized to intravenous KGF (60 μg/kg) or placebo for 3 days, before inhaling 50μg lipopolysaccharide. Six hours later, subjects underwent bronchoalveolar lavage (BAL) to quantify markers of alveolar inflammation and cell-specific injury.

Measurements and Main Results: KGF did not alter leukocyte infiltration or markers of permeability in response to LPS. KGF increased BAL concentrations of Surfactant Protein D (SP-D), MMP-9, IL-1Ra, GM-CSF and CRP. In vitro, BAL fluid from KGF-treated subjects (KGF BAL) inhibited pulmonary fibroblast proliferation, but increased alveolar epithelial proliferation. Active MMP-9 increased alveolar epithelial wound repair. Finally, BAL from the KGF pre-treated group enhanced macrophage phagocytic uptake of apoptotic epithelial cells and bacteria compared with BAL from the placebo-treated group. This effect was blocked by inhibiting activation of the GM-CSF receptor.

Conclusions: KGF treatment increases BAL SP-D, a marker of type II alveolar epithelial cell proliferation in a human model of ALI. Additionally KGF increases alveolar concentrations of the anti-inflammatory cytokine IL-1Ra, and mediators that drive epithelial repair (MMP-9) and enhance macrophage clearance of dead cells and bacteria (GM-CSF).

Wireless Energy Harvesting and Spectrum Sharing in Cognitive Radio

A wireless energy harvesting protocol is proposed for a decode-and-forward relay- assisted secondary user (SU) network in a cognitive spectrum sharing paradigm. An expression for the outage probability of the relay-assisted cognitive network is derived subject to the following power constraints: 1) the maximum power that the source and the relay in the SU network can transmit from the harvested energy, 2) the peak interference power from the source and the relay in the SU network at the primary user (PU) network, and 3) the interference power of the PU network at the relay-assisted SU network. The results show that as the energy harvesting conversion efficiency improves, the relay- assisted network with the proposed wireless energy harvesting protocol can operate with outage probabilities below 20% for some practical applications.

Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily of secreted cysteine knot proteins that includes TGFβ₁, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.

Realizing Accelerated Cost-Effective Distributed RAID

The exponential growth in user and application data entails new means for providing fault tolerance and protection against data loss. High Performance Com- puting (HPC) storage systems, which are at the forefront of handling the data del- uge, typically employ hardware RAID at the backend. However, such solutions are costly, do not ensure end-to-end data integrity, and can become a bottleneck during data reconstruction. In this paper, we design an innovative solution to achieve a flex- ible, fault-tolerant, and high-performance RAID-6 solution for a parallel file system (PFS). Our system utilizes low-cost, strategically placed GPUs — both on the client and server sides — to accelerate parity computation. In contrast to hardware-based approaches, we provide full control over the size, length and location of a RAID array on a per file basis, end-to-end data integrity checking, and parallelization of RAID array reconstruction. We have deployed our system in conjunction with the widely-used Lustre PFS, and show that our approach is feasible and imposes ac- ceptable overhead.

Application of colloidal gas aphron suspensions produced from Sapindus mukorossi for arsenic removal from contaminated soil

Colloidal gas aphron dispersions (CGAs) can be described as a system of microbubbles suspended homogenously in a liquid matrix. This work examines the performance of CGAs in comparison to surfactant solutions for washing low levels of arsenic from an iron rich soil. Sodium Dodecyl Sulfate (SDS) and saponin, a biodegradable surfactant, obtained from Sapindus mukorossi or soapnut fruit were used for generating CGAs and solutions for soil washing. Column washing experiments were performed in down-flow and up flow modes at a soil pH of 5 and 6 using varying concentration of SDS and soapnut solutions as well as CGAs. Soapnut CGAs removed more than 70% arsenic while SDS CGAs removed up to 55% arsenic from the soil columns in the soil pH range of 5–6. CGAs and solutions showed comparable performances in all the cases. CGAs were more economical since it contains 35% of air by volume, thereby requiring less surfactant. Micellar solubilization and low pH of soapnut facilitated arsenic desorption from soil column. FT-IR analysis of effluent suggested that soapnut solution did not interact chemically with arsenic thereby facilitating the recovery of soapnut solution by precipitating the arsenic. Damage to soil was minimal arsenic confirmed by metal dissolution from soil surface and SEM micrograph.

Investigation of Finish-cut of Microelectrodischarge Milling for Nano Surface Finish

In this article, the machining conditions to achieve nanometric surface roughness in finish cut microelectrodischarge milling were investigated. For a constant gap voltage, the effect of feed rate and capacitance was studied on average surface roughness (Ra) and maximum peak-to-valley roughness height (Ry). Statistical models were developed using a three-level, two-factor experimental design. The developed models minimized Ra and Ry by desirability function approach. Maximum desirability was found to be more than 98%. The minimum values of Ra and Ry were 23 and 173 nm, respectively, for 1.00 μm s-1 feed rate and 0.01 nF capacitance. Verification experiments were conducted to check the accuracy of the models, where the responses were found to be very close to the predicted values. Thus, the developed models can be used to generate nanometric level surface finish, which are useful for many applications in microelectromechanical systems.

Investigation of Machining Parameters for Multiple Response Optimization in Microelectrodischarge Milling

This paper investigated the influence of three micro electrodischarge milling process parameters, which were feed rate, capacitance, and voltage. The response variables were average surface roughness (R a ), maximum peak-to-valley roughness height (R y ), tool wear ratio (TWR), and material removal rate (MRR). Statistical models of these output responses were developed using three-level full factorial design of experiment. The developed models were used for multiple-response optimization by desirability function approach to obtain minimum R a , R y , TWR, and maximum MRR. Maximum desirability was found to be 88%. The optimized values of R a , R y , TWR, and MRR were 0.04, 0.34 μm, 0.044, and 0.08 mg min−1, respectively for 4.79 μm s−1 feed rate, 0.1 nF capacitance, and 80 V voltage. Optimized machining parameters were used in verification experiments, where the responses were found very close to the predicted values.

Towards more flexible Architecture Description Languages for industrial applications

Architecture Description Languages (ADLs) have emerged in recent years as a tool for providing high-level descriptions of software systems in terms of their architectural elements and the relationships among them. Most of the current ADLs exhibit limitations which prevent their widespread use in industrial applications. In this paper, we discuss these limitations and introduce ALI, an ADL that has been developed to address such limitations. The ALI language provides a rich and flexible syntax for describing component interfaces, architectural patterns, and meta-information. Multiple graphical architectural views can then be derived from ALI's textual notation.

Performance Evaluation of Two-Stage Electrokinetic Washing as Soil Remediation Method for Lead Removal using Different Wash Solutions

The study explores the application of a two-stage electrokinetic washing system on remediation of lead (Pb) contaminated soil. The process involved an initial soil washing, followed by an electrokinetic process. The use of electrokinetic process in soil washing not only provided additional driving force for transporting the desorbed Pb away from the soil but also reduced the high usage of wash solution. In this study, the effect of NaNO3, HNO3, citric acid and EDTA as wash solutions on two-stage electrokinetic washing system were evaluated. The results revealed that a two-stage electrokinetic washing process enhanced Pb removal efficiency by 2.52-9.08% and 4.98-20.45% in comparison to a normal electrokinetic process and normal washing process, respectively. Low pH and adequate current were the most important criteria in the removal process as they provided superior desorption and transport properties. The effect of chelating by EDTA was less dominant as it delayed the removal process by forming a transport loop in anode region between Pb ion and complexes. HNO3 was not suitable as wash solution in electrokinetic washing in spite of offering highest removal efficiency as it caused pH fluctuation in the cathode chamber, corroded graphite anode and showed high power consumption. In contrast, citric acid not only yielded high Pb removal efficiency with low power consumption but also maintained a low soil: solution ratio of 1 g: <1 mL, stable pH and electrode integrity. Possible transport mechanisms for Pb under each wash solution are also discussed in this work.

Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery

The design of a non-viral gene delivery vehicle capable of delivering and releasing a functional nucleic acid cargo intracellularly remains a formidable challenge. For systemic gene therapy to be successful a delivery vehicle is required that protects the nucleic acid cargo from enzymatic degradation, extravasates from the vasculature, traverses the cell membrane, disrupts the endosomal vesicles and unloads the cargo at its destination site, namely the nucleus for the purposes of gene delivery. This manuscript reports the extensive investigation of a novel amphipathic peptide composed of repeating RALA units capable of overcoming the biological barriers to gene delivery both in vitro and in vivo. Our data demonstrates the spontaneous self-assembly of cationic DNA-loaded nanoparticles when the peptide is complexed with pDNA. Nanoparticles were < 100 nm, were stable in the presence of serum and were fusogenic in nature, with increased peptide α-helicity at a lower pH. Nanoparticles proved to be non-cytotoxic, readily traversed the plasma membrane of both cancer and fibroblast cell lines and elicited reporter-gene expression following intravenous delivery in vivo. The results of this study indicate that RALA presents an exciting delivery platform for the systemic delivery of nucleic acid therapeutics.

The CACTOS Vision of Context-Aware Cloud Topology Optimization and Simulation

Recent advances in hardware development coupled with the rapid adoption and broad applicability of cloud computing have introduced widespread heterogeneity in data centers, significantly complicating the management of cloud applications and data center resources. This paper presents the CACTOS approach to cloud infrastructure automation and optimization, which addresses heterogeneity through a combination of in-depth analysis of application behavior with insights from commercial cloud providers. The aim of the approach is threefold: to model applications and data center resources, to simulate applications and resources for planning and operation, and to optimize application deployment and resource use in an autonomic manner. The approach is based on case studies from the areas of business analytics, enterprise applications, and scientific computing.

Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia

Background Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.

Methods Adult sheep (30–40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10¹¹ CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10⁶ hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10⁶ hMSCs/kg, n=4.

Results By 24 h, the PaO₂/FiO₂ ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO₂/FiO₂ of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9–5.8] vs control: 6.7 g wet/g dry [IQR 6.4–7.5] (p=0.01)). The hMSCs had no adverse effects.

Conclusions Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.

Operator systems from discrete groups

We express various sets of quantum correlations studied in the theoretical physics literature in terms of different tensor products of operator systems of discrete groups. We thus recover earlier results of Tsirelson and formulate a new approach for the study of quantum correlations. To do this we formulate a general framework for the study of operator systems arising from discrete groups. We study in detail the operator system of the free group Fn on n generators, as well as the operator systems of the free products of finitely many copies of the two-element group Z2. We examine various tensor products of group operator systems, including the minimal, the maximal, and the commuting tensor products. We introduce a new tensor product in the category of operator systems and formulate necessary and sufficient conditions for its equality to the commuting tensor product in the case of group operator systems.

Characterisations of the weak expectation property

We use representations of operator systems as quotients to deduce various characterisations of the weak expectation property (WEP) for C∗ -algebras. By Kirchberg’s work on WEP, these results give new formulations of Connes’ embedding problem.

Interactions of a non-thermal atmospheric pressure plasma effluent with PC-3 prostate cancer cells

The effect of a radio-frequency driven, microscale non thermal atmospheric pressure plasma jet operated in helium with vol. 0.3% molecular oxygen gas admixture, on PC-3 prostate cancer cells has been investigated. The viability of cells exposed to the plasma was found to decrease with increasing plasma exposure time, with apoptosis through caspase and PARP cleavage being observed. High concentrations of nitrite and nitrate were detected in growth media exposed to the plasma and were found to increase in a time dependent manner post exposure. This indicates a slow release of reactive nitrogen species into the growth media, which is likely to influence cellular response to plasma exposure.