Preparation of polyethylene glycol/polyacrylamide adduct and utilization in cotton finishing

Highly concentrated aqueous solutions of acrylamide (Am) were polymerized in presence of polyethylene glycol (PEG) using ammonium persulfate as initiator under different conditions including ammonium persulfate concentration (0.02–0.06 g/gAm) temperature (60–95 °C), Am/PEG400 ratio (1/1–1/5 g/g), PEG molecular weight (400–6000). At optimum reaction conditions a PEG 400/PAm adduct was prepared with a % total conversion of 99.7 in 2 min using ammonium persulfate (0.05 g/gAm), Am/PEG (1/2 g/g) at 70 °C. The structure of the adduct was confirmed by FT-IR spectra. The adduct was utilized as a finishing additive for cotton fabric in presence and absence of dimethyloldihydroxy ethylene urea (DMDHEU) by the bad – dry – cure method. In absence of DMDHEU, the adduct improves the fabric tensile strength, stiffness and oily stain release rating without affect the wettability along with decreasing the fabric resiliency compared to the blank sample. Inclusion DMDHEU the finishing bath (50 g/l) results in improving the fabric resiliency and stiffness as well as decreasing the strength, wettability and oily stain release compared to those of fabric treated with adduct in absence of DMDHEU. However, at an adduct concentration of 40 g/l and in presence of 50 g/l DMDHEU the fabric properties are in general, superior to those of blank fabric.     

Viral Nanoparticles for In vivo Tumor Imaging

The use of nanomaterials has the potential to revolutionize materials science and medicine. Currently, a number of different nanoparticles are being investigated for applications in imaging and therapy. Viral nanoparticles (VNPs) derived from plants can be regarded as self-assembled bionanomaterials with defined sizes and shapes. Plant viruses under investigation in the Steinmetz lab include icosahedral particles formed by Cowpea mosaic virus (CPMV) and Brome mosaic virus (BMV), both of which are 30 nm in diameter. We are also developing rod-shaped and filamentous structures derived from the following plant viruses: Tobacco mosaic virus (TMV), which forms rigid rods with dimensions of 300 nm by 18 nm, and Potato virus X (PVX), which form filamentous particles 515 nm in length and 13 nm in width (the reader is referred to refs. ¹ and ² for further information on VNPs).From a materials scientist''s point of view, VNPs are attractive building blocks for several reasons: the particles are monodisperse, can be produced with ease on large scale in planta, are exceptionally stable, and biocompatible. Also, VNPs are "programmable" units, which can be specifically engineered using genetic modification or chemical bioconjugation methods ³. The structure of VNPs is known to atomic resolution, and modifications can be carried out with spatial precision at the atomic level⁴, a level of control that cannot be achieved using synthetic nanomaterials with current state-of-the-art technologies.In this paper, we describe the propagation of CPMV, PVX, TMV, and BMV in Vigna ungiuculata and Nicotiana benthamiana plants. Extraction and purification protocols for each VNP are given. Methods for characterization of purified and chemically-labeled VNPs are described. In this study, we focus on chemical labeling of VNPs with fluorophores (e.g. Alexa Fluor 647) and polyethylene glycol (PEG). The dyes facilitate tracking and detection of the VNPs ^5-10, and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics ^8,11. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect¹². The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease.     

Cardioprotection from ischemia-reperfusion injury due to Ras-GTPase inhibition is attenuated by glibenclamide in the globally ischemic heart

The present study was designed to see if acute local inhibition of Ras-GTPase before or after ischemia (during perfusion) would produce protection against ischemia and reperfusion (I/R)-induced cardiac dysfunction. The effect of glibenclamide, an inhibitor of cardiac mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels, on Ras-GTPase-mediated cardioprotection was also studied. A 40 min episode of global ischemia followed by a 30 min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (P(max)) and left ventricular end-diastolic pressure (LVEDP). Perfusion with Ras-GTPase inhibitor FPT III before I/R [FPT(pre)], significantly enhanced cardiac recovery in terms of left ventricular contractility. P(max) was significantly higher at the end of 30 min reperfusion in FPT(pre)-treated hearts compared to pre-conditioned hearts. However, the degree of improvement in left ventricular contractility was significantly less when FPT III was given only after ischemia during reperfusion [FPT(post)]. Combination treatment with FPT III and glibenclamide before I/R resulted in significant reduction of FPT III-mediated cardioprotection. These data suggest that activation of Ras-GTPase signaling pathways during ischemia are critical in the development of left ventricular dysfunction and that opening of mitoK(ATP) channels, at least in part, contributes to cardioprotection produced by Ras-GTPase inhibition.     

Cutaneous Collateral Axonal Sprouting Re-Innervates the Skin Component and Restores Sensation of Denervated Swine Osteomyocutaneous Alloflaps

Reconstructive transplantation such as extremity and face transplantation is a viable treatment option for select patients with devastating tissue loss. Sensorimotor recovery is a critical determinant of overall success of such transplants. Although motor function recovery has been extensively studied, mechanisms of sensory re-innervation are not well established. Recent clinical reports of face transplants confirm progressive sensory improvement even in cases where optimal repair of sensory nerves was not achieved. Two forms of sensory nerve regeneration are known. In regenerative sprouting, axonal outgrowth occurs from the transected nerve stump while in collateral sprouting, reinnervation of denervated tissue occurs through growth of uninjured axons into the denervated tissue. The latter mechanism may be more important in settings where transected sensory nerves cannot be re-apposed. In this study, denervated osteomyocutaneous alloflaps (hind- limb transplants) from Major Histocompatibility Complex (MHC)-defined MGH miniature swine were performed to specifically evaluate collateral axonal sprouting for cutaneous sensory re-innervation. The skin component of the flap was externalized and serial skin sections extending from native skin to the grafted flap were biopsied. In order to visualize regenerating axonal structures in the dermis and epidermis, 50um frozen sections were immunostained against axonal and Schwann cell markers. In all alloflaps, collateral axonal sprouts from adjacent recipient skin extended into the denervated skin component along the dermal-epidermal junction from the periphery towards the center. On day 100 post-transplant, regenerating sprouts reached 0.5 cm into the flap centripetally. Eight months following transplant, epidermal fibers were visualized 1.5 cm from the margin (rate of regeneration 0.06 mm per day). All animals had pinprick sensation in the periphery of the transplanted skin within 3 months post-transplant. Restoration of sensory input through collateral axonal sprouting can revive interaction with the environment; restore defense mechanisms and aid in cortical re-integration of vascularized composite allografts.     

JNK modulates the effect of caspases and NF-kappaB in the TNF-alpha-induced down-regulation of Na+/K+ATPase in HepG2 cells

An inhibition of the Na(+)/K(+)ATPase was previously shown to accompany and potentiate apoptosis in different experimental models. Since TNF-alpha is known to be a pro and anti-apoptotic cytokine, this work was undertaken to study the effect of TNF-alpha on the Na(+)/K(+)ATPase in HepG2 cells and to determine the signaling pathway involved. Cells were incubated for 1 h with TNF-alpha in presence and absence of PDTC, SP600125 and FK009, respective inhibitors of NF-KB, c-JNK, and caspases. The activity of the pump was assayed by measuring the ouabain-inhibitable release of inorganic phosphate, and changes in its expression were monitored by western blot analysis. TNF-alpha decreased significantly the activity and protein expression of the Na(+)/K(+)ATPase. NF-kappaB and caspases were found to be the main effectors of the cytokine, mediating respectively down-regulation and up-regulation of the pump. Their activity was however modulated at 1 h by c-JNK, which stimulated the caspases and inhibited NF-kappaB, resulting in a net inhibition of the ATPase, and probably favoring the apoptotic pathway.     

Characterization of three lactic acid bacteria and their isogenic ldh deletion mutants shows optimization for YATP (cell mass produced per mole of ATP) at their physiological pHs

Several lactic acid bacteria use homolactic acid fermentation for generation of ATP. Here we studied the role of the lactate dehydrogenase enzyme on the general physiology of the three homolactic acid bacteria Lactococcus lactis, Enterococcus faecalis, and Streptococcus pyogenes. Of note, deletion of the ldh genes hardly affected the growth rate in chemically defined medium under microaerophilic conditions. However, the growth rate was affected in rich medium. Furthermore, deletion of ldh affected the ability for utilization of various substrates as a carbon source. A switch to mixed acid fermentation was observed during glucose-limited continuous growth and was dependent on the growth rate for S. pyogenes and on the pH for E. faecalis. In S. pyogenes and L. lactis, a change in pH resulted in a clear change in Y(ATP) (cell mass produced per mole of ATP). The pH that showed the highest Y(ATP) corresponded to the pH of the natural habitat of the organisms.     

Tissue temperature feedback control of power: the key to successful ablation

Multiple ablation technologies are used to treat atrial fibrillation during cardiac operations. All such ablation technologies use locally induced temperature extremes (>50°C or <-20°C) to kill tissue and create a lesion pattern in the atria which blocks activation pathways that initiate and sustain atrial fibrillation. The technologies used to heat tissue have included radiofrequency (RF), microwave, high-intensity focused ultrasound, and infrared laser. RF accounts for more than 95% of the heating-based ablation technology used by cardiac surgeons. Energy delivery with RF is easier to control than with some other technologies, the heating produced by the energy source is well understood, and manufacturing costs are not excessive. Whichever heating technology is used, control of energy delivery is required to ensure both safe and effective heating of the targeted tissue. All targeted tissue needs to be heated above 50°C to achieve cell death. However, the targeted tissue should not be heated above 100°C, as this can cause perforation due to a steam pop. In addition, adjacent noncardiac tissues must not be damaged during the ablation procedure. The best method to achieve this control uses direct measurement of tissue temperature, because the tissue temperature defines both the safe and effective limits for the ablative process.     

1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design,synthesis, antiproliferative activity,apoptotic effect,and in silico studies

In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.     

HybridFlood: minimizing the effects of redundant messages and maximizing search efficiency of unstructured peer-to-peer networks

Peer-to-peer systems are important Internet applications. A major portion of Internet traffic belongs to such applications. Flooding search is a basic search scheme for unstructured peer-to-peer networks, where a node must send a query message to all its neighbors when seeking a file (in a file sharing situation). Flooding has no knowledge about network topology and files distribution, thus it offers an attractive method for file discovery in dynamic and evolving networks. Although pure flooding can achieve high coverage but it produces exponentially redundant messages in each hop. Consequently, the growth of redundant messages limits system scalability and causes unnecessary traffic in networks. Besides, flooding has no opportunity to get an advantage of node diversity of participating in unstructured P2P networks. To improve this searching scheme and reduce redundant messages, this paper proposes a novel algorithm named HybridFlood. This algorithm is divided into two steps. The first step follows the flooding with a limited number of hops. In the second step, nosey nodes are selected in each searching horizon. The nosey nodes are nodes which have the most links to other nodes. These nodes maintain the data index of all client nodes. We provided analytical studies for flooding and HybridFlood. The analytical results provided the best threshold point of hop for optimum coverage growth rate and redundant messages in flooding. It also proved in HybridFlood broadcasting messages are cut down at least an order of magnitude. Thus, the proposed algorithm extends the search efficiency by reducing redundant messages in each hop. The simulation experiments validated analytical results.