Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Report for General Research December 26, 1950 to April 16, 1951 (Supporting Research Volume)

This volume presents the quarterly results of that portion of the research and development which is directed towards establishing new techniques and instruments and towards improving present methods for determining levels of radioactivity accurately and safely. The locally developed amplifier of high gain and of wide dynamic range has been shown to provide plateaus suitable for the simultaneous counting of alpha and beta particles. Commercially available amplifiers have failed to exhibit suitable plateaus when used under the same conditions. This locally developed amplifier in conjunction with the Nuclear Instruments PC1 chamber has made it possible to estimate beta energies down to 0.02 million electron volt, which is to be compared to a former lower limit of 0.1 million electron volt. A fast neutron survey meter must be simple, lightweight, portable and efficient and must provide discrimination against gamma rays. The first step, which is the design of a suitable detecting device has been successfully completed as good efficiency and good discrimination against gamma rays have been achieved. The necessary electronic circuits must now be engineered to provide the requisite simplicity lightweight and portability

Report for General Research September 18 to December 11, 1950 (Radium Volume)

The purpose of the research work reported in this volume is the development of a process for the separation and subsequent purification of radium from the K-65 (pitchblende) residue. Except for the accumulation of additional experimental data the process is essentially complete. After a preliminary extraction of about 85% of the lead and 40% of the silica with a 40% sodium hydroxide solution, the residue is treated with a solution containing both sodium hydroxide and sodium carbonate to obtain additional lead removal and partial conversion of the radium and barium sulfates to carbonates. After leaching out the soluble carbonates, the residue containing unconverted sulfates is treated with a sodium carbonate solution at 170{sup o} under pressure. A study of the amount and concentration of sodium carbonate required to obtain a satisfactory conversion of the sulfates has shown that the total sodium carbonate may be reduced by 40% and that smaller volumes of solution may be employed without serious decrease in the efficiency of the conversion. In order to make calculations on the number of steps and tank sizes for the radium-barium separation by fractional precipitation, equations have been developed to calculate this information from the theoretical separation factors determined experimentally. Three methods for carrying out the radium-barium separation by fractional precipitation of chromates have been studied and the separation factors determined. The methods differ in the reagent and temperature employed for the neutralization of the nitric acid solution of the chromates. The separation factor improves with decrease in temperature, and a marked improvement has been found by replacing urea which requires boiling temperatures for hydrolysis with potassium cyanate which hydrolyzes at much lower temperatures

Report for General Research September 18 to December 11, 1950 (Actinium Volume)

The purpose of the research work presented in this volume is to develop a process for the separation and purification of actinium-227 produced by neutron bombardment of radium-226 and to develop methods by which uniform films of actinium metal may be deposited on metallic surfaces. The design work on the cave structure and mechanical equipment used in the actinium separation is proceeding on schedule. As the mechanical design phase is nearing completion the emphasis is being directed toward processing equipment. The process as well as the mechanical equipment has been adapted from the research work of F. T. Hagemann and the Remote Control Group at Argonne National Laboratory. Consequently, one of the first objectives is to become familiary with the chemistry of the process and the operation of the mechanical equipment. Cold runs have been made on the T.T.A. benzene extraction using lanthanum and barium in place of actinium and radium. No difficulty with the operation was observed. The formation of precipitates was one of the difficulties encountered with the process as the precipitates carry radium. It has been found that metals such as nickel cause these precipitates to form and should, therefore, be avoided in the construction of equipment. it was also found that a T.T.A. solution exposed to 0.5 curie of polonium over a period of days develops a precipitate. Some new mechanical features hav eshown promise. The use of copper-coated glassware which will hold together even though the glass is cracked has made it possible to replace custom-built heaters with standard heating mantles. A new graphite, silicone grease mixture appears to hold up in stopcocks handling benzene and, as a result, may eliminate the necessary of entering the cave for regreasing. Tests on the preparation of dense concrete have given results which meet the shielding requirements for the cave. A strippable paint and tape combination has been studied and specified to provide for decontamination of the interior of the cave. A number of different methods for the preparation of actinium metal are being tested with lanthanum compounds. It has not been found possible to reduce lanthanum from liquid ammonia with metallic sodium. Electrolytic methods are being investigated. Preliminary work has been started in an effort to determine polarographically the reduction potential of lanthanum from various fused salts. An attempt to obtain lanthanum metal from the iodide by the DeBoer proces is also under way. Lanthanum iodide vapor is thermally decomposed at a tungsten filament and the iodine vapor pumped from the system

Report for General Research August 7 to October 30, 1950

Investigation of the physical and chemical properties of polonium important to its behavior and for the improvement of the quantity and quality produced is being continued. A sample of polonium is approximatelyf 1 x 10{sup 9} disintegrations per minute was counted in a Logac for 250 days in order to determine the half life. A statistical treatment of the results gave a half life of 138.3562 {+-} 0.446 days. Combined with previous calorimetric determinations a new grand mean of 138.3975 {+-} 0.0091 days resulted. The wavelengths of 138 lines appearing in the spark spectrum between 3050A and 3463A (Region 4) have been tentatively assigned to polonium and have a probable error of less than 0.02A. Thirty six lines in Region 6 (4225A to 5675A) tentatively assigned to polonium have a probable error of less than D D6A. A measurement of the resistivity of polonium has given a value of about 95 microohm centimeters, and although the Hall voltage could not be measured with much precision, it was possible to set a maximum value of 0.03 millivolt. These values indicate the polonium is a metallic conductor rather than a semiconductor. A rugged but compact gauge made of stainless steel with a tantalum diaphragm has been constructed to have a good sensitivity for the vapor pressure measurement of polonium tetrachloride. Studies by X-ray methods have shown that platinum nickel, and silver form compounds with polonium under the conditions of preparation, while tantalum, gold stainless steel, and beryllium do not. Bismuth formed an alloy of no definite composition which could be separated into its components at 485{sup o} Silver plonide decomposed at 559{sup o}

Report for General Research July 10 to October 2, 1950 (Supporting Research Volume)

The efficient prosecution of the research and process development on polonium, radium, actinium, waste disposal, and alpha-neutron sources requires the use of a wide variety of instrumental techniques such as: alpha, beta, gamma, and neutron counters and survey meters; emission, absorption, and mass spectroscopy: x-ray and electron diffraction; microbalances; and calorimeters. The complex and kaleidoscopic aspects of our research program require; (1) The application of standard instruments and techniques to a variety of problems; (2) The development of new techniques for the use of standard instruments; and (3) The development of new or improved Instruments. The sum of the above three categories constitutes the field of supporting research. The amplifier for counting pulses of wide dynamic range which was developed for counting beta particles in the presence of alphas has operated so satisfactorily that it has been decided to attempt to adopt it for neutron counting. Substantial improvement at medium counting rates has already been obtained but results at high counting rates are not as satisfactory. The development of a survey meter for monitoring fast neutrons has been under way for sometime. The attainment of higher efficiency has been attempted by the use of a dual-chambered counter tube. The tube operates with a filling of methane gas at two atmospheres pressure. The achievement of leak-proof seals and highest purity methane has been under investigation as their necessity has been indicated by tests. The development of a scintillation counter for surveying and measuring low levels of alpha activity has been continued. Recent efforts have been directed towards determining the correct voltages to be applied to the photomultiplier tube in order to operate under optimum conditions. Recent tests of the coincidence counter to detect scintillations in water containing alpha-active waste material have indicated the necessity of obtaining photomultiplier tubes with low noise level and a better regulated, noise-free power supply