Enhancement of tumor killing using a combination of tumor immunization and HSV-tk suicide gene therapy

Tumor cells genetically modified with the herpes simplex virus thymidine kinase (HSV-tk) gene in combination with ganciclovir (GCV) demonstrate a "bystander effect". Previous attempts to enhance the bystander tumor killing by combining cytokine genes with HSV-tk/GCV have met with varying results. The present study was designed to determine the effects of tumor immunization in combination with HSV-tk gene-modified tumor cells and GCV on tumor killing and to determine if the bystander tumor killing could be enhanced. Tumor-bearing mice immunized with syngeneic tumor (KBALB) prior to treatment with an i.p. injection of xenogeneic HSV-tk gene-modified tumor cells (PA-1STK) had prolonged animal survival (group 4, 56.4 days). In contrast, unimmunized tumor-bearing mice (group 2) or tumor-bearing mice immunized to the xenogeneic PA-1STK tumor cells (group 5) showed a mean survival of about 27 days after receiving an i.p. injection of PA-1STK cells and GCV. Control groups, which were either not immunized and did not receive HSV-tk cells (group 1) or immunized but treated only with GCV (group 3) showed short survival (16-18 days). Analysis of tumors for cytokine mRNA expression revealed increased TNF-alpha and IL-1alpha mRNA expression in group 4 mice. Furthermore, IL-2 mRNA expression was detectable on days 2 and 4 only in group 4 mice. Immunophenotypic analysis for tumor-infiltrating lymphocytes demonstrated an increase in macrophage (4%, p = 0.0001) and T cells (1.8%, p < 0.001) in group 4 mice with an enhanced T-cell response as compared with mice from groups 1, 2 and 3. Our results demonstrate that tumor immunization combined with HSV-tk/GCV treatment results in increased animal survival with enhanced immune response. Furthermore, the cytokine milieu observed in the present study can modulate the tumor micro-environment in vivo from one that is immunosuppressive to one that is immune-stimulatory.     

Stomach implant for long-term erythropoietin expression in rats

Caveolae are small microdomains of the plasma membrane that are thought to play important roles in signal transduction processes. In this work, we have investigated the association of Rho proteins with caveolae-enriched membrane domains isolated from cultured endothelial cells. Fractionation of ECV304 cells by sucrose gradient density centrifugation in the absence of detergent resulted in the co-sedimentation of a significant proportion of RhoA and Cdc42 with known caveolae marker proteins, including caveolin, but not with other non-caveolae membrane proteins such as the angiotensin-converting enzyme. Immunoprecipitation experiments carried on crude endothelial cell lysates as well as with solubilized caveolae-enriched membrane domains showed the coimmunoprecipitation of caveolin with RhoA but not with Cdc42. Incubation of endothelial cell lysates with a glutathione-S-transferase (GST)-RhoA fusion protein resulted in the specific precipitation of caveolin, while addition of GST-caveolin-1 to the lysates promoted the precipitation of RhoA. Moreover, incubation of bacterially expressed RhoA with GST-caveolin-1 resulted in the precipitation of RhoA, indicating that RhoA directly interacts with caveolin-1. This interaction was found to be nucleotide-independent and was not affected by prior modification of RhoA with the C3 exoenzyme from C. botulinium or with the cytotoxic necrotinizing factor from E. coli. Taken together, these results suggest the association of RhoA with endothelial caveolae-enriched membrane domains, likely through physical interaction with caveolin-1. These findings may provide new insights into the functions played by Rho proteins and caveolae in signal transduction events.     

Set size, novelty, and visual pop-out in infancy.

The effects of set size and novelty on visual pop-out in 6-month-old infants was assessed in a perceptual-identification (memory reactivation) paradigm in which infants, trained and tested in their own homes, viewed a mobile containing a unique novel or familiar object amidst different numbers of familiar or novel distractors, respectively. Unique objects of both types popped out at all set sizes except the largest, where there was modest evidence that familiar distractors speeded processing (Experiment 1). When the proportion of familiar targets in a display of intermediate set size was increased, however, infants no longer detected the familiar target (Experiment 2). These findings offer additional support for the proposition that visual pop-out in infants and adults is the same phenomenon. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Electrochemical characterization of binderless, recompressed exfoliated graphite electrodes: electron-transfer kinetics and diffusion characteristics

Exfoliated graphite (EG) is prepared by the thermal exfoliation of graphite intercalation compounds at different temperatures. Surface and bulk physicochemical properties of EG are followed by spectroscopic and analytical methods and are observed to be a function of exfoliation temperature. EG particles can be recompressed without any binder and used as surface-renewable electrodes. Surface preparation is accomplished by either polishing or roughening the electrode surface using emery sheets. Effects of exfoliation temperature and the surface preparation on the electron-transfer kinetics and on the diffusion characteristics have been followed by electrochemical methods using several benchmark redox systems. It is found that the electron-transfer kinetics and the diffusion of K(4)[Fe(CN)(6)] are affected by the nature of the EG surface while that of iron(II)(1,10-phenanthroline)(3) and cobalt(II)(1,10-phenanthroline)(3) are not affected by the surface preparation. The redox systems are classified into different groups according to their kinetic sensitivity. Diffusion of electroactive species toward the EG electrodes is found to nonlinear. Current-time plots suggest that the recompressed EG electrodes can be modeled as fractals.     

Porous PZT ceramics for receiving transducers

PZT-air (porous PZT) and PZT-polymer (polymer impregnated porous PZT) piezocomposites with varying porosity/polymer volume fractions have been manufactured. The composites were characterized in terms of hydrostatic charge (d/sub h/) and voltage (g/sub h/) coefficients, permittivity, hydrostatic figure of merit (d/sub h/.g/sub h/), and absolute sensitivity (M). With decreasing PZT ceramic volume, g/sub h/ increased, and d/sub h/.g/sub h/ had a broad maximum around 80 to 90% porosity/polymer content. The absolute sensitivity was also increased. In each case, PZT-air piezocomposites performed better than PZT-polymer piezocomposites. Hydrophones constructed from piezocomposites showed slightly lower measured receiving sensitivities than calculated values for piezocomposite materials, which was due to the loading effect of the cable and the low permittivity associated with the piezocomposites.     

Efficient Update of Indexes for Dynamically Changing Web Documents

Recent work on incremental crawling has enabled the indexed document collection of a search engine to be more synchronized with the changing World Wide Web. However, this synchronized collection is not immediately searchable, because the keyword index is rebuilt from scratch less frequently than the collection can be refreshed. An inverted index is usually used to index documents crawled from the web. Complete index rebuild at high frequency is expensive. Previous work on incremental inverted index updates have been restricted to adding and removing documents. Updating the inverted index for previously indexed documents that have changed has not been addressed. In this paper, we propose an efficient method to update the inverted index for previously indexed documents whose contents have changed. Our method uses the idea of landmarks together with the diff algorithm to significantly reduce the number of postings in the inverted index that need to be updated. Our experiments verify that our landmark-diff method results in significant savings in the number of update operations on the inverted index.     

Application of Fuzzy Logic to Estimate Flow of Methane for Energy Generation at a Sanitary Landfill

This paper proposes the use of a multicriteria assessment technique to evaluate the methane flow during gas extraction from a sanitary landfill. A number of parameters determine the gas generation and the feasibility for its extraction from a landfill. These parameters form a complex set of information with unknown mathematical interrelationships making potential gas flow evaluations difficult and elusive. In addition, the data available for a particular landfill are very often imprecise, uncertain, or subjective, making it even more difficult to evaluate the potential for gas extraction without conducting pilot tests. The method proposed in this paper uses fuzzy composite programming that allows for the use of imprecise information. A landfill gas potential index has been defined, which can be determined by easily obtainable climatological, geological, and landfill parameters. The landfill gas (LFG) potential index is related to the landfill gas flow using an empirical equation. The LFG potential model was calibrated and verified using data obtained from 61 landfills where gas extraction is being conducted. A sensitivity analysis was done to study the impact of variations in the input data on model output.     

The effect of manganese oxide on the sinterability of hydroxyapatite

The sinterability of manganese oxide (MnO₂) doped hydroxyapatite (HA) ranging from 0.05 to 1 wt% was investigated. Green samples were prepared and sintered in air at temperatures ranging from 1000 to 1400 °C. Sintered bodies were characterized to determine the phase stability, grain size, bulk density, hardness, fracture toughness and Young's modulus. XRD analysis revealed that the HA phase stability was not disrupted throughout the sintering regime employed. In general, samples containing less than 0.5 wt% MnO₂ and when sintered at lower temperatures exhibited higher mechanical properties than the undoped HA. The study revealed that all the MnO₂-doped HA achieved >99% relative density when sintered at 1100-1250 °C as compared to the undoped HA which could only attained highest value of 98.9% at 1150 °C. The addition of 0.05 wt% MnO₂ was found to be most beneficial as the samples exhibited the highest hardness of 7.58 GPa and fracture toughness of 1.65 MPam^1/2 as compared to 5.72 GPa and 1.22 MPam^1/2 for the undoped HA when sintered at 1000 °C. Additionally, it was found that the MnO₂-doped samples attained E values above 110 GPa when sintered at temperature as low as 1000 °C if compared to 1050 °C for the undoped HA.     

Performance Analysis of UWB Channels for Wireless Personal Area Networks

Ultra-wide band (UWB) communication is one of the most promising technology for high data rate networks over short-range communication. The ultra-wide bandwidth offers pulses with very short duration that provides frequency diversity and multipath resolution. Ultra-wide band (UWB) channels raise new effects in the receiver, the amplitude fading statistics being different compared to the conventional narrow band wireless channels. This review paper focuses on modeling of ultra-wide band channels, especially for simulation of personal area networks and also discusses the benefits, application potential and technical challenges in wideband communication. The concept of Orthogonal Frequency Division Multiplexing (OFDM) has recently been applied in wireless communication systems due to its high data rate transmission capability with high bandwidth efficiency and its robustness to multi-path delay. UWB OFDM communication was proposed for physical layer in the IEEE 802.15.3a standard which covers wideband communication in wireless personal area networks. Since the channel model for multicarrier UWB communication is different from that of plain ultra-wide band channel, a novel modification method in UWB channel model is proposed with specific center frequency and multipath resolution. Moreover, dynamic channel estimation is necessary before demodulation of UWB OFDM signals since the radio channel is time varying and frequency selective for wideband systems. The performance of the proposed method is statistically analyzed using LS and MMSE based channel estimation methods.     

Collocation-based stochastic finite element analysis for random field problems

A stochastic response surface method (SRSM) which has been previously proposed for problems dealing only with random variables is extended in this paper for problems in which physical properties exhibit spatial random variation and may be modeled as random fields. The formalism of the extended SRSM is similar to the spectral stochastic finite element method (SSFEM) in the sense that both of them utilize Karhunen–Loeve (K–L) expansion to represent the input, and polynomial chaos expansion to represent the output. However, the coefficients in the polynomial chaos expansion are calculated using a probabilistic collocation approach in SRSM. This strategy helps us to decouple the finite element and stochastic computations, and the finite element code can be treated as a black box, as in the case of a commercial code. The collocation-based SRSM approach is compared in this paper with an existing analytical SSFEM approach, which uses a Galerkin-based weighted residual formulation, and with a black-box SSFEM approach, which uses Latin Hypercube sampling for the design of experiments. Numerical examples are used to illustrate the features of the extended SRSM and to compare its efficiency and accuracy with the existing analytical and black-box versions of SSFEM.