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The alpha-factor receptor (STE2) stimulates a G protein signaling pathway that promotes mating of the yeast Saccharomyces cerevisiae. Previous random mutagenesis studies implicated residues in the regions near the extracellular ends of the transmembrane domains in ligand activation. In this study, systematic Cys scanning mutagenesis across the ends of transmembrane domains 5 and 6 identified two residues, Phe(204) and Tyr(266), that were important for receptor signaling. These residues play a specific role in responding to alpha-factor since the F204C and Y266C substituted receptors responded to an alternative agonist (novobiocin). To better define the structure of this region, the Cys-substituted mutant receptors were assayed for reactivity with a thiol-specific probe that does not react with membrane-imbedded residues. A drop in reactivity coincided with residues likely to be buried in the membrane. Interestingly, both Phe(204) and Tyr(266) are located very near the interface region. However, these assays predict that Phe(204) is accessible at the surface of the receptor, consistent with the strong defect in binding alpha-factor caused by mutating this residue. In contrast, Tyr(266) was not accessible. This correlates with the ability of Y266C mutant receptors to bind alpha-factor and suggests that this residue is involved in the subsequent triggering of receptor activation. These results highlight the role of aromatic residues near the ends of the transmembrane segments in the alpha-factor receptor, and suggest that similar aromatic residues may play an important role in other G protein-coupled receptors.

The introduction of counter tubes and the related instrument geometries have made it possible to obtain greatly improved x-ray powder patterns. Most of the important factors that must be understood in x-ray diffractometry are described in terms of their effect on the intensity, peak-to-background ratio, resolution and line shape. These factors are the geometry of the x-ray optical system, the x-ray tube focal spot size, the angular apertures of the primary beam in the focusing and axial planes, the 2: 1 setting, and the receiving slit. The precision is often limited by the specimen preparation rather than the instrument, and the effects of homogeneity, displacement and transparency, crystallite sizes, and preferred orientation are outlined. A new diffractometer arrangement employing a transmission specimen followed by a focusing crystal monochromator is shown to be a useful supplement to the standard reflecting specimen diffractometer for clay mineral studies. The important characteristics of Geiger, proportional and scintillation counters are described in terms of linearity, quantum counting efficiency, pulse amplitude distribution and counting statistics. A bibliography of key literature references is appended.

It is vital that U.S. academic institutions pay heed to the important global challenges that HS academics and practitioners must face. This article finds in an overview of the development of prescriptions for curricular outcomes and competencies for homeland security education in the U.S. that there has been little emphasis on curricular goals in the U.S. of the transnational and global application of homeland security strategies and operations. Transatlantic links in homeland security education between U.S. universities and their counterparts in Europe will be hampered by the virtual lack of explicit academic programs in this field in that continent. An examination of program goals and curricular offerings in U.S. post-baccalaureate programs indicates a modest attempt to provide students some grounding in transnational and global applications of homeland security strategies and operations.

Methods for precise control of the cutting angles of quartz by x-ray measurements are described. The quartz must first be oriented by some other method (usually optically) before the x-ray method can be applied. The sense of direction of the cut is indicated by an arrow drawn on the outer surface of the test cut at the saw and this direction is preserved in making the x-ray measurement. The x-ray technique is an adaptation of the Bragg ionization chamber method and involves measuring the angle between the surface of the test cut or blank and an atomic reference plane parallel (or nearly parallel) to the surface. All measurements are direct, and require no computation. A Gieger-Muller tube operated in the proportional counter region is employed. Accuracy of the method is approximately ±1.5′, the measurement requires about 10-15 seconds, and is used by unskilled help. The procedures for calibrating the x-ray goniometer and measuring various types of cuts are described in detail. Methods involving precise angular adjustments of sections approximately oriented by other methods and the use of reflection intensity differences of certain planes on either side of the optic axis for detecting usable portion of electrical twins and negative and positive directions from Z are described. The methods are applicable to other fields.

A procedure for the accurate determination of unit-cell parameters using conventional Xray powder diffractometry is described. Two important factors in the procedure are: 1) the use of high-resolution-type diffractometer, which can suppress the axial beam divergence and thus gives nearly symmetric diffraction profiles in the low 2θ region and 2) the use of a new algorithm for systematic peak shift correction during the least-squares determination of unit-cell parameters of a sample with an internal standard [Toraya & Kitamura (1990). J. Appl. Cryst. 23 , 282-285]. The procedure has been tested by measuring successively the unit-cell parameter of W, CeO2, and Si in three mixtures, Si+W, W+CeO2, and CeO2+Si: the unit-cell parameter of W, which was first determined by using NIST SRM 640b Si powder as an internal standard reference material, was used as a standard reference value to determine the unit-cell parameter of CeO; in the next W+CeO2 mixture, and so on. The difference between the end value of observed Si unit-cell parameters and the starting value of 5.430940(35) Å were just 1 to 5 p.p.m. High accuracy is attainable in measuring the uni-cell parameters even with the conventional powder diffractometry provided with the nearly symmetric diffraction profile and the algorithm for peak shift correction used in the present study.

High-mobility group box-1 (HMGB1) protein was originally described as a nuclear DNA-binding protein that functions as a structural cofactor critical for proper transcriptional regulation and gene expression. Recent studies indicate that damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it functions as a proinflammatory cytokine. Indeed, HMGB1 represents a novel family of inflammatory cytokines composed of intracellular proteins that can be recognized by the innate immune system as a signal of tissue damage. Posttranslational modifications of HMGB 1 determine its interactions with other proteins and modulate its biological activity. However, very little is known about how these posttranslational modifications of HMGB1 affect its extracellular inflammatory activity and pathological potential. These studies can provide more efficient therapeutic strategies directed against specific HMGB1 isoforms. Therapeutic strategies against these specific HMGB1 isoforms can serve as models for more efficient therapeutic strategies against rheumatoid arthritis or sepsis. This article reviews the recent studies on HMGB1 regulation and their impact on the inflammatory activity and pathological contribution of HMGB 1 to infectious and inflammatory disorders.

The inflammatory reflex is a neural circuit that regulates innate immune responses to endotoxin and other stimulating agents. It confers protection against damaging inflammation by inhibiting synthesis and release of TNF and other cytokines. Action potentials transmitted in the vagus nerve stimulate acetylcholine release, a neurotransmitter which inhibits cytokine production by interacting with a7nAChR expressed on macrophages and other cytokine-producing cells. We studied the effects of electrical stimulation of the vagus nerve, and observed that a brief period of neural stimulation resulted in suppression of TNF release that persisted for several days. To deconvolute this effect, we implanted vagus nerve stimulators in ambulatory canines, and found that brief electrical pulses significantly inhibited endotoxin-induced TNF release for up to 9 days. Exposure of isolated monocytes and macrophages to acetylcholine reduced TNF production for 24 h via signal transduction through a7nAChR. a7nAChR interaction with type 6 adenylate cylcase upregulated cAMP levels, and enhanced phosphorylation of CREB. Transfection of monocytes with a dominant negative CREB blocked the prolonged deactivation of monocytes exposed transiently to acetylcholine or a7nAChR agonists. Thus, signals originating as action potentials in the vagus nerve produce an a7nAChR - CREB dependent deactivated phenotype in monocytes, which has significant implications for understanding the regulation of innate immunity.

The central nervous system regulates innate immunity reflexively, as action potentials transmitted in the vagus nerve suppress cytokine release during endotoxemia. The mechanism of cytokine release by this neural circuit requires signaling through the alpha 7 nicotinic acetylcholine receptor (a7 nAChR), but the duration of this protection is incompletely understood. Electrical vagus nerve stimulation (VNS) in mice significantly inhibited serum TNF levels during endotoxemia, even when endotoxin was given 2, 24 or 48 h after VNS. This inhibition of TNF was abolished in a7 nAChR deficient mice, confirming the mechanism that requires this receptor. One-hour exposure of human macrophages to acetylcholine in vitro reduced endotoxin-induced increases in IKKbeta, IkappaBalpha activity and TNF release for up to 24 h after removal of acetylcholine. Levels of Supressor of Cytokine Signaling 1-3, A20, BCL3, IkappaBNS and IkappaBzeta were not altered in human macrophages 15 min to 8 h after exposure to acetylcholine, but exposure of macrophages to the selective JAK/STAT inhibitor AG490 abolished the cytokine suppressing effect of acetylcholine. Together with previous work indicating that JAK/STAT forms a signaling complex with a7 nAChR, these results suggest that JAK/STAT activation is required for long lasting suppression of macrophage cytokine release after transient exposure to acetylcholine.

This paper describes the principles, methods, instrumentation and results of EDXKD and a computer method of profile fitting to obtain corrected intensities and peak energies from isolated and overlapping reflections. The profile, P, of a diffraction peak is a convolution of the incident X-ray spectrum, X, the geometrical aberrations, T, the contribution from the specimen, S, and the detector resolution function, D.

The analysis of mixtures of phases which produce complicated composite x-ray powder patterns is greatly facilitated by use of our profile fitting method and the technique of applying it is illustrated with a five-compound mixture. Profile fitting gave higher precision in the determination of the reflection angles and Intensities and resolved overlaps in a much shorter time than with other methods. If the reference standards are obtained with the same precision, a smaller error window width can b e used in the search/match procedure.

The Kα satellites occur as a group of weak, unresolved lines superimposed on the short wavelength tail of the Kα1 line. Satellite data obtained experimentally with a single‐crystal diffractometer are reported and compared with the results of two‐crystal spectrometer measurements by previous investigators. It is calculated from spectral data that the addition of the satellite group to the Kα1,2 lines shifts the Cu centroid 0.031 xu and the Fe centroid 0.061 xu to shorter wavelengths. The satellites occur superimposed on the short wavelength tail of the Kα1 line in back‐reflection powder line profiles and appear as a low intensity ``plateau'' which may cause difficulties in precision measurements. The effect of the satellite group on the value of the centroid obtained by various methods of truncating the profile is described. The angular separation of the satellites from the Kα1 component increases with increasing diffraction angles and may cause an error of the order of 1% in the relative integrated line intensities if the integration limits do not consistently include or exclude the satellites.

The relative rms deviation σ of the intensity of a rapidly rotating polycrystallite specimen is σ=[6.5R sinθ]/[h(mNeff)½], where R=goniometer radius, θ=Bragg angle, h=(hf+hs)/2, hf=length of focal spot, hs=length of receiving slit, m=multiplicity factor, and Neff the effective number of irradiated crystallites. Experimental data on silicon powder specimens are presented to show the dependence of σ on crystallite sizes, choice of x‐ray wavelengths and various other experimental parameters. Comparisons of data for rapidly rotating and stationary specimens having crystallite sizes in the 30–50 μ range show that rotation improves σ by a factor of 7 or 8 for peak intensities and 4 or 5 for integrated intensities, using a standard diffractometer.

The intensity distribution and dimensions of the x‐ray tube focus can be recorded accurately and rapidly by scanning with a pair of molybdenum rod slits and a scintillation counter. Two methods were used: (1) the image‐forming slit mounted near the x‐ray tube remains fixed and the image is scanned with another slit mounted on the detector; (2) both slits and detector are translated as a unit across the focus. The vignetting was analyzed and can be made negligible in both methods. Magnification of the image is not possible with method (2), but it has the advantage of minimum vignetting and easier alignment.

For an exact solution of the Bragg equation it is necessary that there be a one-to-one correspondence (equivalence) between the angnlar measure theta and the wavelength measure lambda . Because the aberrations inherent in all x- ray diffraction profile measurements distont the profile, it is necessary to correct any given measure (peak, centroid, etc.) for all aberrations. The only angular measure of powder diffractometer profiles that can be corrected to a high degree of accuracy is the centroid. To realize the greater accuracy inherent in the centroid method, accurate centroid spectral wavelengths are required. Centroids of CuK alpha and FeK alpha two-crystal spectrometer profiles prepared by Bearden were calculated and corrected for axial divergence, distortions arising from variation in absorption across the spectral distributions, crystal asymmetry, and other factors. To determine the centroid wavelength it is necessary to truncate the profile; equivalence of lambda and theta is maintained by truncating the powder and spectral profiles in the same manner. Four methods for systematically truncating the profiles have been published; the methods are evaluated and the superiority of one of the methods is demonstrated. It is shown that the centroid wavelength is a function of integration (wavelength) range, primarily as amore » result of inclusion or exclusion of the K alpha satellite group within the truncated profile. The twocrystal spectrometer profiles are compared with models based on a Cauchy distribution. The necessity for additional spectral data before reference centroid wavelengths can be established is discussed.« less

Mass absorption coefficient data published by Allen, Bragg, and Victoreen for the wavelength region 0.1 to 50 A are plotted for several common x‐ray tube and counter windows (Al, Be, and mica) and gases (Xe, Kr, A, and Ne) used in x‐ray detectors. A graph of the calculated percentage transmission of the windows is presented. The calculated quantum‐counting efficiencies for the range 0.1 to 15 A are shown for an end‐window argon‐filled Geiger counter, side‐window Xe, Kr, A, and Ne proportional counters and an NaI·Tl scintillation counter. Some of the factors to be considered in the choice of detectors for x‐ray diffractometry and x‐ray spectroscopy are discussed particularly with respect to the spectral sensitivity.

This paper reviews the factors in diffractometer geometry most likely to cause large errors in intensity measurements due to imperfect specimen preparation, particularly preferred orientation. It is recommended the same specimen be transferred to two or more diffractometer geometries in which the specimen has different orientations to obtain sets of complementary data. Three geometries are illustrated: θ-2θ scanning with reflection and transmission specimens, and Seeman-Bohlin with reflection specimen.

The introduction of counter tubes and the related instrument geometries have made it possible to obtain greatly improved x-ray powder patterns. Most of the important factors that must be understood in x-ray diffractometry are described in terms of their effect on the intensity, peak-to-background ratio, resolution and line shape. These factors are the geometry of the x-ray optical system, the x-ray tube focal spot size, the angular apertures of the primary beam in the focusing and axial planes, the 2: 1 setting, and the receiving slit. The precision is often limited by the specimen preparation rather than the instrument, and the effects of homogeneity, displacement and transparency, crystallite sizes, and preferred orientation are outlined. A new diffractometer arrangement employing a transmission specimen followed by a focusing crystal monochromator is shown to be a useful supplement to the standard reflecting specimen diffractometer for clay mineral studies. The important characteristics of Geiger, proportional and scintillation counters are described in terms of linearity, quantum counting efficiency, pulse amplitude distribution and counting statistics. A bibliography of key literature references is appended.

Comparative diffractometer measurements were made with several radiations and a NaI · Tl scintillation counter with pulse‐height discrimination. Figures of merit for the different wavelengths based on intensity and peak‐to‐background ratio of a silicon powder specimen were: CuKα 100, MoKα 32, CrKα 10, and WLα 6. Several factors contributing to the figure of merit are discussed.

Geiger counter x‐ray diffractometer patterns of samples with moderate to high radioactivity give a high background, which reduces the precision of the x‐ray‐line intensity and profile measurements. The large amount of lead shielding required to reduce the background is not practical in modern precision goniometers and could not bring as great a reduction as can be achieved with scintillation or proportional counters using pulse‐height discrimination and no shielding. This paper describes a technique using a scintillation counter which permits the measurement of x‐ray patterns from strongly radioactive specimens. A scintillation counter with 0.56 in.×0.16 in.×0.017 in. thick NaI·Tl crystal, 0.005 in. Be window and DuMont 6291 photomultiplier is described, which reduced the background of an 84 mr/hr/10 cm Co60 sample from 785 c/sec, measured with a Geiger counter, to 26 c/sec and increased the sensitivity to CuKα by a factor of about 2.5 to 3.

Escape peaks occur when the incident X-ray quantum, energy exceeds the absorption edge energy of the detector element and the resulting X-ray fluorescence is lost from the detector. The most common escape peaks result from 1 K-fluorescence in NaI-scintillation counters and Xe K-, Xe L-, and Kr K-fluorescence in proportional counters. The average pulse amplitude of the escape peak is proportional to the difference of the Energies of the incident and fluorescent X-rays. If the intensity of the escape peak is high as in the case of Mo Kα and a kryptoopreportional counter, and the lower level of the pulse height analyzer is raised to reject the escape peak, the quantum counting efficiency may be reduced by a factor of two. When the pulse height analyzer is set for characteristic incident radiation, escape peaks appear in powder patterns at small diffraction angles. These broad low-intensity peaks are often mistakenly identified as resulting from misalignment, scattering, etc. Each powder reflection can produce its own escape peak which occurs at an angle slightly smaller than the absorption edge of the detector element. In a silicon powder pattern the three strongest reflections produce three resolved escape peaks whose peak intensities are about 4% of their corresponding Cu Kα peaks when the X-ray tube is operated at 50 kV. The escape peak intensities decrease with decreasing X-ray tube voltage and disappear when the voltage is lower than the absorption edge energy of the detector element. Absorption edge peaks observed without the upper level of the pulse height analyzer are similar in appearance, intensity, and diffraction angle to the escape peaks. In complex powder patterns the escape peak pattern is unresolved and may produce a number of very broad peaks.

After more than a year's study and discussion the members of the American Society for X‐Ray and Electron Diffraction and the Crystallographic Society of America have voted to form a single new society, the American Crystallographic Association. This new organization will eliminate the problems caused by the overlapping interests and memberships of the two previous societies but it is planned to continue similar types of meetings and publications. It now has about 500 members including physicists, chemists, physical chemists, mineralogists, metallurgists, mathematicians, and biologists from universities, government, and private research foundations and industrial research laboratories.

Computer aided design as an engineering tool has permeated all aspects of the infrared sensor industry. The availability and low cost of computer design tools allows a wide spectrum of engineering challenges to be impacted by computer aided design. This paper presents a practical view of the power and applicability of computer aided design. This paper draws on current design experience for infrared detector performance modeling, analog multiplexer performance analysis, integrated circuit mask layout, and infrared sensor test. Practical examples of each design task are reviewed.

An automatic computer method for deriving the intensities, widths, and positions from experimental x‐ray diffraction and energy spectroscopy data is outlined. Complex overlapping clusters of peaks can be resolved and the data are corrected for aberrations.

Expressions are derived relating counting rate measured with quantum detectors to the dosage rate in roentgens. The number of quanta/cm2 per roentgen is strongly energy dependent. In the x‐ray region 5 to 50 kv, however, the variation of the quantum counting efficiency with wavelength of some counters (e.g., argon Geiger counter) matches fairly closely the energy dependence factor, and hence such detectors can be used as r‐meters.

The winter meeting of the American Society for X‐ray and Electron Diffraction was held at Battelle Memorial Institute, Columbus, Ohio, December 16–18, 1948.

The advantages of synchrotron radiation for X-ray polycrystalline diffraction are illustrated by a number of examples. The plane wave parallel-beam X-ray optics uses a Si(lll) channel monochromator for easy wavelength selection and a set of long parallel slits to define the diffracted beam. The constant simple instrument function and the high resolution symmetrical profiles (FWHM 0.05") greatly simplify the data analysis and add a new dimension to profile broadening studies. The geometry permits uncoupling the 6-26 sample-detector relationship without changing the profile shape and makes possible new applications such as grazing angle incidence depth analysis of thin films. The same instrumentation is used for high resolution energy dispersive diffraction (BOD) by step-scanning the monochromator. The resolution is two orders of magnitude better than conventional BOD and can be used at high count rates. The easy wavelength selection yields diffraction patterns with the highest PI B and permits anomalous scattering studies.