Identification of spherical virus particles in digitized images of entire electron micrographs

Interferon-gamma (IFN-gamma) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-gamma in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-gamma (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-gamma therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses > or =0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN-gamma reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-gamma has been shown to have significant effects on the T-cell compartment of the immune system.     

Use of solid phase extraction disks for the GC-MS analysis of acidic and neutral herbicides in drinking water

An analytical procedure was developed in which thirteen herbicides (10 acidic and 3 neutral compounds) may be extracted from drinking water samples using solid phase extraction disks and subsequently analyzed by gas chromatography-mass spectrometry. Using 8 replicate samples consisting of reagent water fortified with nanogram quantities of each herbicide, the average percent recoveries and method detection limits were determined for each analyte. The method was found to be suitable for the determination of individual herbicides in drinking water at concentrations of approximately 10 ng/L.     

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q

The degree and nature of patient involvement in consultations with health professionals influences problem and needs recognition and management, and public accountability. This paper suggests a framework for understanding the scope for patient involvement in such consultations. Patients are defined as co-producers of formal health services, whose potential for involvement in consultations depends on their personal rights, responsibilities and preferences. Patients' rights in consultations are poorly defined and, in the National Health Service (NHS), not legally enforceable. The responsibilities of patients are also undefined. I suggest that these are not to deny, of their own volition, the rights of others, which in consultations necessitate mutuality of involvement through information-exchange and shared decision-making. Preferences should be met insofar as they do not militate against responsibilities and rights.     

Efficient fault-tolerant multicast scheme for hypercubemulticomputers

This paper presents a fault-tolerant multicast scheme for hypercube multicomputers. The method is based on the routing capability information that is stored in each node. In comparison with the previous schemes, this information is able to capture the fault status more precisely. Two multicast algorithms are presented in the paper. These algorithms multicast messages in an attempt to minimize derouting so that time optimality can be achieved. Moreover, the routing capability information is used to guide derouting in an efficient manner when such needs arise. The amount of traffic incurred is addressed in the paper. The hardware design for the algorithms is also discussed. Extensive simulation has been conducted to evaluate the performance of the scheme. The results show the effectiveness of the proposed algorithms     

Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry

OBJECTIVE: To characterize changes of Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) that occur during the course of HIV infection by cytoplasmic cytokine staining on single cell level. DESIGN AND METHODS: Mitogen-stimulated PBMC from 16 healthy donors, 18 HIV-1-infected individuals without AIDS and 14 patients with AIDS were stained intracellularly with fluorescein-labelled MAb against interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-gamma. Additionally, co-staining of CD4+ T-cell, CD8+ T-cell, natural killer (NK) cell, B-cell and monocytic markers was performed. Fluorescence staining was analysed by three-colour flow-cytometry. RESULTS: A reduced percentage of IL-2 and IFN-gamma (Th1 type)-producing cells among CD4+ T cells from HIV-1-infected individuals could be demonstrated. There was a continuous decrease of IFN-gamma-producing CD4+ T cells in the course of HIV infection and a dramatic reduction of IL-2-expressing cells among CD4+ T cells in patients with AIDS. In contrast to Th1 cytokines, the frequency of Th2 cytokine expressing cells among CD4+ T cells increased in HIV-infected individuals. The maximum frequency of IL-4-expressing cells among CD4+ T cells was seen in HIV-infected individuals without AIDS, whereas the rate of IL-10-producing cells was highest in patients with AIDS. In HIV-infected individuals no significant proportion of Th0 cells expressing both Th1 and Th2 cytokines was detectable. In CD8+ T cells the percentage of IL-2 was expressing cells decreased continuously accompanied by a strong increase of the frequency of IFN-gamma-producing cells. CONCLUSION: The decreased percentage of cells expressing IL-2 and IFN-gamma in conjunction with an increased proportion of IL-4- and IL-10-producing cells among the CD4+ T cells in HIV-1-infected individuals demonstrate a Th1 to Th2 cytokine shift in the course of HIV infection on a single cell level. There was no evidence of a Th1 to Th0 cytokine shift. In addition to the loss of CD4+ T cells in HIV infection, the qualitative changes of Th1/Th2 cytokine expression may serve as a marker for progressive failure of cell-mediated immunity.     

An atomic model of the outer layer of the bluetongue virus core derived from X-ray crystallography and electron cryomicroscopy

BACKGROUND: Bluetongue virus (BTV), which belongs to the Reoviridae family and orbivirus genus, is a non-enveloped, icosahedral, double-stranded RNA virus. Several protein layers enclose its genome; upon cell entry the outer layer is stripped away leaving a core, the surface of which is composed of VP7. The structure of the trimeric VP7 molecule has previously been determined using X-ray crystallography. The articulated VP7 subunit consists of two domains, one which is largely alpha-helical and the other, smaller domain, is a beta barrel with jelly-roll topology. The relative orientations of these two domains vary in different crystal forms. The structure of VP7 and the organizations of 780 subunits of this molecule in the core of virus is central to the assembly and function of BTV. RESULTS: A 23 A resolution map of the core, determined using electron cryomicroscopy (cryoEM) data, reveals that the 260 trimers of VP7 are organized on a rather precise T = 13 laevo icosahedral lattice, in accordance with the theory of quasi-equivalence. The VP7 layer occupies a shell that is between 260 A and 345 A from the centre of the core. Below this radius (230-260 A) lies the T = 1 layer of 120 molecules of VP3. By fitting the X-ray structure of an individual VP7 trimer onto the cryoEM BTV core structure, we have generated an atomic model of the VP7 layer of BTV. This demonstrates that one of the molecular structures seen in crystals of the isolated VP7 corresponds to the in vivo conformation of the molecule in the core. CONCLUSIONS: The beta-barrel domains of VP7 are external to the core and interact with protein in the outer layer of the mature virion. The lower, alpha-helical domains of VP7 interact with VP3 molecules which form the inner layer of the BTV core. Adjacent VP7 trimer-trimer interactions in the T = 13 layer are mediated principally through well-defined regions in the broader lower domains, to form a structure that conforms well with that expected from the theory of quasi-equivalence with no significant conformational changes within the individual trimers. The VP3 layer determines the particle size and forms a rather smooth surface upon which the two-dimensional lattice of VP7 trimers is laid down.     

Aging and mechanical properties of NR/BR blends

The mechanical properties and post-thermal aging properties of natural rubber (NR) and polybutadiene rubber (BR) blends at different blending ratios are investigated herein. The experimental results show that both tensile and tear strengths of NR/BR blends increase with increasing NR content. BR has a higher compression stiffness than NR. The deformation of BR is less than that of NR under the same load conditions. With regard to aging properties, both tensile stress and strain of NR/BR blends decrease after prolonged aging. In addition, the stress loss of BR is lower than that of NR, meaning that the aging resistance property of BR is superior to that of NR. Furthermore, accumulated thermal history has shifted the glass transition temperature (T _g) of NR/BR blends toward lower temperatures while the loss tangent (tan δ) value increases with prolonged thermal aging.     

Influence of volatile matter and deposited carbon on coke yield from coals

The relations between coke yields and the volatile matter content of 30 individual and 30 blended coals were investigated. Coke yields and deposited carbon related to volatile matter content can be expressed in the following equations: CY (%) = 97.89?0.86 VMch+VMc; and DC (%)= ?2.24+0.16 VMch; where: CY=real coke yield; VMch = volatile matter content of charging coal; VMc=volatile matter content of coke, and in the case of <2%; DC = deposited carbon. The test results show excellent correlation with practice.     

Electrochemical pitting behaviour of type 321 stainless steel in sulfide-containing chloride solutions

The pitting behaviour of type 321 stainless steel in sulfide-containing chloride aqueous environments was studied using cyclic potentiodynamic polarization. A well-established correlation between H₂S and Na₂S₂O₃ in the study of corrosion was applied, that is, H₂S was simulated by Na₂S₂O₃. The major factors affecting the pitting corrosion of type 321 stainless steel are the Cl^- concentration, solution pH and temperature. The results clearly indicate that both E_pit and E _pp decrease with increasing Cl^- concentration and temperature, while I _pass is more sensitive to temperature variation. E _pit decreased with decreasing pH in the range 2 < pH < 7.5. The surface morphology and chemistry of the corroded type 321 stainless steel resulting from anodic polarization in 0.01 M S₂O ₃ ^2- -containing Cl^- solution were analysed by XRD, SEM and EPMA. A higher concentration of sulfur was found in the pits, and the dark surface film was mainly composed of FeS and -Fe₂O₃. The results describe the pitting behaviour of type 321 stainless steel in sulfide-containing Cl^- aqueous environments.