Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells

This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-gamma genes were introduced and expressed in MBT-2 cells. The tumor-forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice.     

Variants of fractionation of irradiation in intracavitary gamma-therapy

Under study was the efficacy of three schedules of dose fractionation in intracavitary gamma-therapy in cervical cancer patients treated on the machine "AGAT-B". Single doses were 1000, 700 and 500 rad, while total dosage at point A depending on the stage of the disease was within the range of 4000-5000 rad. The survival during the first, second and third years following termination of the radiotherapy was found to be identical for patients of all the groups under examination. No differences were noted in them also in the character of early radiation reactions on the part of the adjacent organs. The frequency and severity of late radiation injuries of the urinary bladder, rectum and vagina were related to the dose fractionation regimen.     

Heat denaturation of hemocytocardiotoxin from the venom of the Central Asian cobra

It has been stated that boiled for three hours haemocytocardiotoxin (HT) from cobra poison loses "direct" hemolytic activity and is unable to potentiate a haemolytic effect of phospholipase A. Surface activity of HT does not change. It is shown that in the course of heat denaturation the aggregation of toxin molecules to dimers and trimers takes place and electrophoretic mobility is decreased. The fluorescence of HT tyroxin residues supported the fact of its irreversible heat denaturation.     

A new device for performing reference point indentation without a reference probe

Here we describe a novel, hand-held reference point indentation (RPI), instrument that is designed for clinical measurements of bone material properties in living patients. This instrument differs from previous RPI instruments in that it requires neither a reference probe nor removal of the periosteum that covers the bone, thus significantly simplifying its use in patient testing. After describing the instrument, we discuss five guidelines for optimal and reproducible results. These are: (1) the angle between the normal to the surface and the axis of the instrument should be less than 10°, (2) the compression of the main spring to trigger the device must be performed slowly (>1 s), (3) the probe tip should be sharper than 10 μm; however, a normalized parameter with a calibration phantom can correct for dull tips up to a 100 μm radius, (4) the ambient room temperature should be between 4?°C and 37 °C, and (5) the effective mass of the bone or material under test must exceed 1 kg, or if under 1 kg, the specimen should be securely anchored in a fixation device with sufficient mass (which is not a requirement of previous RPI instruments). Our experience is that a person can be trained with these guidelines in about 5 min and thereafter obtain accurate and reproducible results. The portability, ease of use, and minimal training make this instrument suitable to measure bone material properties in a clinical setting.     

Network level bridges maintenance planning using Multi-Attribute Utility Theory

Bridge infrastructure managers are facing multiple challenges to improve the availability and serviceability of ageing infrastructure, while the maintenance planning is constrained by budget restrictions. Many research efforts are ongoing, for the last few decades, ranging from development of bridge management system, decision support tools, optimisation models, life cycle cost analysis, etc. Since transport infrastructures are deeply embedded in society, they are not only subject to technical requirements, but are required to meet the requirements of societal and economic developments. Therefore, bridge maintenance planning should accommodate multiple performance goals which need to be quantified by various performance indicators. In this paper, an application of Multi-Attribute Utility Theory (MAUT) for bridge maintenance planning is illustrated with a case study of bridges from the Netherlands road network. MAUT seeks to optimise multiple objectives by suggesting a trade-off among them and finally assigns a ranking to the considered bridges. Moreover, utility functions of MAUT appropriately account for the involved uncertainty and risk attitude of infrastructure managers. The main contribution of this study is in presenting a proof-of-concept on how MAUT provides a systematic approach to improve the decision-making of maintenance planning by making use of available data, accommodating multiple performance goals, their uncertainty, and preferences of infrastructure managers.     

Investigation of the effects of recycled engine oil bottoms on asphalt field performance following an oxidation modeling approach

This work investigates the effects of recycled engine oil bottoms (REOBs) on asphalt field performance by comparing asphalts with and without REOBs in terms of the asphalt properties required for pavement oxidation modeling. Specifically, oxidation reaction kinetics parameters, dynamic shear rheometer (DSR) function (DSRFn) hardening susceptibility (HS), and low sheer viscosity (LSV) HS are determined and compared for base binder, 5 wt.% REOBs, and 15 wt.% REOBs blends. At the higher percentage, addition of REOBs appears to increase the initial oxidation rate at field temperatures and significantly increases LSV HS, but does not significantly increase the DSRFn HS. A field modeling example elucidates the effects.     

Low temperature cure of epoxy thermosets attaining high Tg using a uniform microwave field

It is demonstrated for the first time that an epoxy thermoset resin can be cured at temperatures well below its T_g∞. This study compared the use of a uniform variable frequency microwave (VFM) field to standard oven curing at temperatures above and below T_g∞. Using T_g, tan δ, modulus, and FTIR measurements, it is shown that the reaction of BFDGE with MDA to attain a product with T_g∞ of 133 °C is achieved by VFM at temperatures from 100 to 140 °C; in contrast, the thermal cure normally requires 170 °C to attain the same T_g∞ and the same extent of cure. By following the pregel cure reaction with ¹³C‐NMR spectroscopy, it was determined that the lower cure temperatures of VFM cure predominately lead to chain extension and smaller amounts of crosslinking compared to the thermal cure. To explain these results, it is suggested that, after gelation, with VFM cure there is higher mobility from dipole rotations that continues the cure to completion without vitrification. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44222.     

Statewide investigation of the role of pyrethroid pesticides in sediment toxicity in California's urban waterways

A statewide investigation of urban creek sediment toxicity was conducted in California in recognition of increased incidences of toxicity linked to pyrethroid pesticides. The goals were to examine the spatial occurrence and magnitude of sediment toxicity in California urban creeks, and to examine the role of pyrethroids in toxic urban creek sediment samples. After a preliminary screening of 90 sites, 30 creeks were sampled in eight geographical regions. Sediment toxicity was assessed using 10 day bioassays with the resident amphipod Hyalella azteca. Bioassays were conducted at two test temperatures of 23 degrees C and at 15 degrees C to provide evidence of the cause of toxicity, and to more accurately reflect ambient environmental temperatures. Twenty-five of 30 samples were toxic when tested at 23 degrees C, and all 30 samples were toxic when tested at 15 degrees C. The magnitude of toxicity increased in samples tested at 15 degrees C suggesting the influence of pyrethroids, which are more toxic at colder temperatures. Pyrethroids were present in all sediment samples and were the only compounds detected at concentrations toxic to H. azteca. Bifenthrin was the pyrethroid of greatest toxicological concern, occurring in all 30 samples at concentrations up to 219 ng/g. Pyrethroid contamination of urban creeks was most severe in the Los Angeles, Central Valley, and San Diego regions, respectively. However, pyrethroids were also linked to urban creek aquatic toxicity in all regions sampled, including the less urbanized areas of the North Coast and Lake Tahoe.