Impact energy measurement in time-of-flight mass spectrometry with cryogenic microcalorimeters

Time-of-flight mass spectrometry-most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry-is an important class of techniques for the study of proteins and other biomolecules. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there has been limited success in achieving good mass resolution at higher masses. This is because the sensitivity of the microchannel plate (MCP) detectors used in most systems decreases rapidly with increasing particle mass, limiting the utility of MCP detectors for very large masses. It has recently been proposed that cryogenic particle detectors may provide a solution to these difficulties. Cryogenic detectors measure the thermal energy deposited by the particle impact, and thus have a sensitivity that is largely independent of particle mass. Recent experiments have demonstrated the sensitivity of cryogenic particle detectors to single biomolecules, a quantum efficiency several orders of magnitude larger than the MCP detectors, and sensitivity to masses as large as 750,000 daltons. Here we present results demonstrating an order of magnitude better energy resolution than previous measurements, allowing direct determination of particle charge state during acceleration. Although application of these detectors to practical mass spectrometry will require further development of the detectors and cryogenics, these detectors can be used to elucidate the performance-limiting processes that occur in such systems.     

Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.     

Iron bioavailability from diets containing isolated or intact sources of lignin

This paper deals with the development of computerized brain atlases addressing both research and clinical needs. The authors analyze in detail the potential of these systems and discuss the capabilities and limitations of the digital atlases currently being developed around the world. The authors propose to reconsider the concept of a brain atlas, regarding both its content, and the way it has to be used and managed in order to set up more effective cooperation between the user and the system. Particular emphasis is placed on extensibility and reuse issues. which are critical in this rapidly evolving field. These orientations result from both the authors' experience and the analysis of current trends in the field of neuroimaging. The general methodology is illustrated with examples related to computer aided surgical planning.     

In vitro effects of GM-CSF on mature peripheral blood neutrophils

GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.     

Reproductive performance and fertility testing in strain 13 and Hartley guinea pigs

A study to test the effects of certain experimental manipulation on the reproductive capacity of male guinea pigs required verifying the fertility of the male guinea pigs before and after manipulation. Methods of testing fertility were evaluated, and normal reproductive data from preexperimental and control groups were tabulated and analyzed. No data from the actual experiments were included. Virgin and proven fertile males were mated with 1 (1:1) or 2 (2:1) virgin or proven fertile females. Inbred (13/N Umm) and conventional (Mfi:CFDH-ML (DH) ) guinea pigs were used. Ninety-five percent of both groups of males were fertile. Eighty-four percent of both groups of females were fertile. Male guinea pigs previously proven fertile had the same subsequent fertility rate as virgin males. Over one-third of the conceptions did not take place during the first estrus cycle (16 da) during which the males and females were mated. Strain 13 and Hartley females had litters of approximately the same size (3.1 vs 3.0), but the neonatal mortality was statistically lower (P less than 0.001) in the Hartley stock (9.3%) than in the Strain 13 guinea pigs (28.4%).     

A resistive-gate In0.53Ga0.47As/InPheterostructure CCD

The first InGaAs/InP charge-coupled device (CCD) is demonstrated, exhibiting a charge transfer efficiency (CTE) of 0.98 at 13 MHz and 1 GHz. Cooling the device improves the CTE to greater than 0.99 at 13-MHz clock frequency. The 0.76-eV In_0.53Ga_0.47As bandgap makes this structure applicable to direct-detection short-wavelength infrared (SWIR) imagers