A Study of the Radiation Tolerance of CVD Diamond to 70 MeV Protons, Fast Neutrons and 200 MeV Pions.

We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 µm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.8±0.9) × 1015 protons/cm2, (1.43±0.14) × 1016 neutrons/cm2, and (6.5±1.4) × 1014 pions/cm2, respectively. By observing the charge induced due to the separation of electron-hole pairs created by the passage of the hadron beam through each sample, on an event-by-event basis, as a function of irradiation fluence, we conclude all datasets can be described by a first-order damage equation and independently calculate the damage constant for 70 MeV protons, fast reactor neutrons, and 200 MeV pions. We find the damage constant for diamond irradiated with 70 MeV protons to be 1.62±0.07(stat)±0.16(syst)× 10-18 cm2/(p µm), the damage constant for diamond irradiated with fast reactor neutrons to be 2.65±0.13(stat)±0.18(syst)× 10-18 cm2/(n µm), and the damage constant for diamond irradiated with 200 MeV pions to be 2.0±0.2(stat)±0.5(syst)× 10-18 cm2/(π µm). The damage constants from this measurement were analyzed together with our previously published 24 GeV proton irradiation and 800 MeV proton irradiation damage constant data to derive the first comprehensive set of relative damage constants for Chemical Vapor Deposition diamond. We find 70 MeV protons are 2.60 ± 0.29 times more damaging than 24 GeV protons, fast reactor neutrons are 4.3 ± 0.4 times more damaging than 24 GeV protons, and 200 MeV pions are 3.2 ± 0.8 more damaging than 24 GeV protons. We also observe the measured data can be described by a universal damage curve for all proton, neutron, and pion irradiations we performed of Chemical Vapor Deposition diamond. Finally, we confirm the spatial uniformity of the collected charge increases with fluence for polycrystalline Chemical Vapor Deposition diamond, and this effect can also be described by a universal curve.

Two-dimensional semi-parametric alignment of chromatograms.

We present a comprehensive alignment algorithm that extends the semi-parametric approach to two dimensions. The algorithm is based on modeling shifts with a two-dimensional "warp function" such that the sample chromatogram - its shifts corrected with the warp function - is adjusted to the reference chromatogram by minimizing the squared intensity difference. A warp function approach has the advantage that overlapping peaks are easily dealt with compared to other proposed two-dimensional algorithms. Another advantage is that missing peaks are allowed if the absence of these peaks has little numerical effect on the warp function computation and if these peaks occur between existing peaks. Performance of the algorithm is demonstrated using GC×GC data from three batches of three diesel oil samples and LC-MS data from a mouse breast cancer data set.

Microarray analysis of bleomycin-exposed lymphoblastoid cells for identifying cancer susceptibility genes.

The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. It is well established that the way in which an individual deals with DNA damage is related to the chance to develop cancer. Mutagen sensitivity is a phenotype that reflects an individual's susceptibility to the major sporadic cancer types, including colon, lung, and head and neck cancer. A standard test for mutagen sensitivity is measuring the number of chromatid breaks in lymphocytes after exposure to bleomycin. The aim of the present study was to search for the pathways involved in mutagen sensitivity. Lymphoblastoid cell lines of seven individuals with low mutagen sensitivity were compared with seven individuals with a high score. RNA was isolated from cells exposed to bleomycin (4 hours) and from unexposed cells. Microarray analysis (19K) was used to compare gene expression of insensitive and sensitive cells. The profile of most altered genes after bleomycin exposure, analyzed in all 14 cell lines, included relatively many genes involved in biological processes, such as cell growth and/or maintenance, proliferation, and regulation of cell cycle, as well as some genes involved in DNA repair. When comparing the insensitive and sensitive individuals, other differentially expressed genes were found that are involved in signal transduction and cell growth and/or maintenance (e.g., BUB1 and DUSP4). This difference in expression profiles between mutagen-sensitive and mutagen-insensitive individuals justifies further studies aimed at elucidating the genes responsible for the development of sporadic cancers.

Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens.

Intermittent exposure to addictive drugs causes long-lasting changes in responsiveness to these substances due to persistent molecular and cellular alterations within the meso-corticolimbic system. In this report, we studied the expression profiles of 159 genes in the rat nucleus accumbens during morphine exposure (14 days, 10 mg/kg s.c.) and drug-abstinence (3 weeks). We used real-time quantitative PCR to monitor gene expression after establishing its sensitivity and resolution to resolve small changes in expression for genes in various abundance classes. Morphine-exposure (5 time points) and subsequent abstinence (6 time points) induced phase-specific temporal gene expression of distinct functional groups of genes, for example, short-term homeostatic responses. Opiate withdrawal appeared to be a new stimulus in terms of gene expression and mediates a marked wave of gene repression. Prolonged abstinence resulted in persistently changed expression levels of genes involved in neuronal outgrowth and re-wiring. Our findings substantiate the hypothesis that this new gene program, initiated upon morphine-withdrawal, may subserve long-term neuronal plasticity involved in the persistent behavioral consequences of repeated drug-exposure.

The value of ventilation scintigraphy after single lung transplantation.

BACKGROUND: A decrease in forced expiratory volume in 1 second (FEV(1)) as a diagnostic criterion for bronchiolitis obliterans syndrome (BOS) after single lung transplantation may be influenced significantly by the presence of the native lung. To quantify and to discriminate between the relative contribution of graft and native lung to the FEV(1), we retrospectively investigated the diagnostic value of combined FEV(1) measurements and ventilation scintigraphy in pulmonary dysfunction after single lung transplantation in 11 recipients with pulmonary vascular disease, 3 with obstructive lung disease, and 3 with restrictive lung disease. METHODS: We assessed function of the native lung and the graft, and subsequently calculated an adjusted grading of BOS by correcting routine FEV(1) measurements using linear interpolation of bi-annual lung ventilation scans. RESULTS: The contribution of the native lung to the total FEV(1) was slight (median, 9%) in recipients with obstructive disease compared with recipients with vascular (38%) or restrictive lung diseases (27%). Adjusted BOS grading was not useful in patients with obstructive disease. In the other patient groups, the onset of adjusted BOS Grade 1 and standard BOS Grade 1 was at a median of 220 days (range, 127-1146 days) and 836 days (184-3065 days), respectively. CONCLUSION: Ventilation scintigraphy is a useful adjunct in the (early) diagnosis of BOS in recipients of single lung transplants who have vascular and restrictive lung diseases.

Long-term quality of life in patients surviving at least 55 months after lung transplantation.

The aim of this study was to examine the long-term effect of lung transplantation on Health Related Quality of Life by studying 28 patients who survived at least 55 months after lung transplantation. Measures included the Nottingham Health Profile, questions concerning lung-specific problems, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-Being, the Karnofsky performance index, and questions concerning activities of daily life. Furthermore, comorbid conditions were measured. Before transplantation patients reported restrictions on almost all quality of life measures. Until approximately 43 months after transplantation there were significant improvements on most dimensions of the Nottingham Health Profile and more patients could walk without dyspnea. Significant improvements occurred with regard to the levels of anxiety, depression, and well being, and the scores on the Karnofsky performance index improved. Activities of daily life could be performed without help by most patients. After approximately 43 months patients experienced more dyspnea, anxiety, depression, and a lower level of well being. The number of patients suffering from a decrease of kidney function, drug treated hyperlipidemia, insulin dependent diabetes mellitus and bronchiolitis obliterans syndrome increased. It may be concluded that patients experience a stable and better overall quality of life after transplantation. Long-term after lung transplantation patients experience a decline on several dimensions of quality of life, which may be explained by an increase of comorbid conditions and Bronchiolitis Obliterans Syndrome.

Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease.

The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse early antigen (EA(D)), and virus capsid antigen (VCA) were studied in a semiquantitative enzyme-linked immunosorbent assay (ELISA) to study antibody patterns in 12 seronegative lung transplant patients, of whom four developed a post-transplant lymphoproliferative disease, and seven seropositive lung transplant patients, all of whom developed a post-transplant lymphoproliferative disease. Immunoblot technique was used as a control. All 12 EBV-seronegative patients had a very limited antibody response that was restricted mainly to VCA antibodies. EA(D) antibodies became detectable in only two patients. Antibody response never preceded clinical diagnosis of post-transplant lymphoproliferative disease in the four EBV-seronegative patients who developed post-transplant lymphoproliferative disease. In the seven seropositive lung transplant patients with post-transplant lymphoproliferative disease, we found a rise in antibody titer in only two patients. Immunoblot analysis confirmed the serological results. In conclusion, EBV-specific antibody patterns after lung transplantation are highly restricted and variable and of limited value for the diagnosis or prognosis of post-transplant lymphoproliferative disease.

Bronchiolar airflow impairment after lung transplantation: an early and common manifestation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival after lung transplantation (LT). In this study we investigate the extent and frequency of airflow limitation after LT and its value for the diagnosis of BOS. METHODS: Flow-volume measurements were analyzed retrospectively in 36 recipients of a bilateral LT, with a median follow-up of 32.9 months. The prevalence and onset of a decline of FEV(1), FEF(25), FEF(50), FEF(75) and MMEF(75/25) were evaluated and subsequently related to the occurrence of Grade 1 BOS. RESULTS: Grade 1 BOS was diagnosed in 16 recipients at a median of 218 (range 88 to 1,007) days after LT. A persistent and significant decrease in FEV(1), FEF(25), FEF(50), FEF(75) and MMEF(75/25) was observed in 23, 24, 30, 32 and 29 patients, respectively. In those patients developing BOS during follow-up this decrease was determined at 147 (55 to 657), 130 (78 to 932), 110 (21 to 573), 103 (32 to 657) and 121 (32 to 657) days after LT (p < 0.0005), respectively. The respective predictive values of these parameters for the occurrence of Grade 1 BOS (within 120 days) were 88%, 60%, 50%, 35% and 41%. CONCLUSION: Bronchiolar dysfunction is a common and early finding after LT. The decrease of FEV(1) in BOS is often preceded by a decrease of bronchial airflow. Airflow markers may be used as an early warning sign for the development of BOS, although their predictive values are moderate.