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OBJECTIVE: Young children are generally considered immunologically naive with respect to influenza exposure opportunities; thus, a 2-dose schedule is recommended when a child is first immunized with conventional influenza vaccine lacking adjuvant. We estimated the effectiveness of a single pediatric dose of AS03-adjuvanted vaccine against hospitalization for confirmed pandemic influenza A/H1N1 (pH1N1) infection in children aged 6 months to 9 years during the fall 2009 vaccination campaign. METHODS: In a matched case-control design, case subjects were children hospitalized for pH1N1 infection in the Fall of 2009, in Quebec, Canada. Controls were nonhospitalized children, matched by age and region of residence. Vaccination status in case subjects and controls was ascertained in relation to the case subject's date of illness onset. Vaccine effectiveness was estimated through conditional logistic regression. RESULTS: The overall effectiveness of a single pediatric dose of vaccine administered ≥14 days before illness onset was 85% (95% confidence interval [CI]: 61% to 94%), varying according to age category but with wide and overlapping CIs: 92% (95% CI: 51% to 99%) in 6–23 month-old children, 89% (95% CI: 34% to 98%) in 2–4 year-olds, and 79% (95% CI: −31% to 96%) in 5–9 year-olds. Overall vaccine effectiveness for immunization ≥10 days before illness onset was slightly lower at 80% (95% CI: 60% to 90%), with similar variation according to age. CONCLUSION: In children aged 6 months to 9 years, a single pediatric dose of the AS03-adjuvanted pH1N1 vaccine was highly protective against hospitalization beginning at 10 and 14 days after vaccination.

Rotavirus is the leading cause of dehydration and hospitalization due to gastroenteritis (GE) in young children. Almost all children are affected by the age of 5 years. Two safe and effective rotavirus vaccines are available for clinical use in Canada. In the context where rotavirus vaccination is recommended, but not publicly funded, we have assessed paediatricians’ knowledge, attitudes and beliefs (KAB) regarding rotavirus disease and its prevention by vaccination. A self-administered anonymous questionnaire based upon the Health Belief Model and the Analytical framework for immunization programs was mailed to all 1852 Canadian paediatricians. The response rate was 50%. The majority of respondents rated consequences of rotavirus infection for young patients as moderate. Sixty-six percent considered that rotavirus disease occur frequently without vaccination and 62% estimated that the disease generates a significant economic burden. Sixty-nine percent of respondents considered rotavirus vaccines to be safe and 61%, to be effective. The reduction of severe GE cases was seen as the main benefit of rotavirus vaccination, while the risk of adverse events was the principal perceived barrier. Fifty-three percent (53%) indicated a strong intention to recommend rotavirus vaccines. In multivariate analysis, main determinant of paediatricians’ intention to recommend rotavirus vaccines was the perceived health and economic burden of rotavirus diseases (partial R2 = 0.49, p

The Fossil Forest Research Natural Area (FFRNA) in New Mexico is the site of an exceptionally preserved fossil forest of Campanian age. This study combines paleoecological, taxonomic, and sedimentological analysis, together with GIS mapping of 68 fossil tree stumps and nine fossil logs, in order to provide a detailed description of this forest. Wood analysis of stumps illustrates that the forest is almost exclusively composed of conifers most likely related to the Cupressaceae. Reconstruction of the forest indicates that the conifers were mature and widely spaced, creating an open canopy woodland; however, leaf litter directly associated with the fossil woodland has not been preserved, so the detailed composition of its understory remains enigmatic. Analysis of the substrate in which the stumps were rooted suggests that trees grew in a gley soil under wet floodplain conditions. Mean sensitivity analysis of growth rings in the stumps indicates that small-scale environmental disturbances on the floodplain, such as periodic flooding, or regional environmental disturbances, such as volcanism, disrupted wood production. The death of the woodland was probably due to waterlogging and burial by suspended sediment associated with flooding. Despite the presumed dominance of angiosperms in disturbed, riparian environments during the Late Cretaceous, this study indicates that conifers were still dominant in some subenvironments at this time and could form mature open canopy woodlands on wet unstable floodplains.

Nucleoside analogs are efficacious cancer chemotherapeutics due to their incorporation into tumor cell DNA. However, they exhibit vastly different antitumor efficacies, suggesting that incorporation produces divergent effects on DNA replication. Here we have evaluated the consequences of incorporation on DNA replication and its fidelity for three structurally related deoxyguanosine analogs: ganciclovir (GCV), currently in clinical trials in a suicide gene therapy approach for cancer, D-carbocyclic 2'-deoxyguanosine (CdG) and penciclovir (PCV). GCV and CdG elicited similar cytotoxicity at low concentrations, whereas PCV was 10-100-fold less cytotoxic in human tumor cells. DNA replication fidelity was evaluated using a supF plasmid-based mutation assay. Only GCV induced a dose-dependent increase in mutation frequency, predominantly GC--TA transversions, which contributed to cytotoxicity and implicated the ether oxygen in mutagenicity. Activation of mismatch repair with hydroxyurea decreased mutations but failed to repair the GC--TA transversions. GCV slowed S-phase progression and CdG also induced a G2/M block, but both drugs allowed completion of one cell cycle after drug treatment followed by cell death in the second cell cycle. In contrast, PCV induced a lengthy early S-phase block due to profound suppression of DNA synthesis, with cell death in the first cell cycle after drug treatment. These data suggest that GCV and CdG elicit superior cytotoxicity due to their effects in template DNA, whereas strong inhibition of nascent strand synthesis by PCV may protect against cytotoxicity. Nucleoside analogs based on the carbohydrate structures of GCV and CdG is a promising area for antitumor drug development.

Suicide gene therapy with herpes simplex virus thymidine kinase and ganciclovir is notable for producing multi-log cytotoxicity in a unique pattern of delayed cytotoxicity in S-phase. Because hydroxyurea, a ribonucleotide reductase inhibitor that activates mismatch repair, can increase sensitivity to ganciclovir, we evaluated the role of MLH1, an essential mismatch repair protein, in ganciclovir cytotoxicity. Using HCT116TK (HSV-TK-expressing) colon carcinoma cells that express or lack MLH1, cell survival studies demonstrated greater ganciclovir sensitivity in the MLH1 deficient cells, primarily at high concentrations. This could not be explained by differences in ganciclovir metabolism, as the less sensitive MLH1-expresssing cells accumulated more ganciclovir triphosphate and incorporated more of the analog into DNA. SiRNA suppression of MLH1 in U251 glioblastoma or SW480 colon carcinoma cells also enhanced sensitivity to high concentrations of ganciclovir. Studies in a panel of yeast deletion mutants confirmed the results with MLH1, and further suggested a role for homologous recombination repair and several cell cycle checkpoint proteins in ganciclovir cytotoxicity. These data suggest that MLH1 can prevent cytotoxicity with ganciclovir. Targeting mismatch repair-deficient tumors may increase efficacy of this suicide gene therapy approach to cancer treatment.

We report on the application of a compact and field-deployable instrument, based on a continuous-wave fiber-coupled Telecom external cavity diode laser, to measure the 13C/12C isotope ratio in CO2 from a wood-based combustion. Carbon dioxide, the most important greenhouse gas, is a major product of combustion. The measurements of the 13C/12C isotopic ratio in CO2 from combustion emission permit one to identify the CO2 source and to study the temporal and spatial variations of pollution in the atmosphere. The average value of the 13CO2/12CO2 ratio is found to be (1.1011±0.0024)%. The corresponding δ-value relative to PDB standard is (−20.17±2.14)‰, which is in good agreement with the typical value of (−25±2)‰ for wood. Simultaneous monitoring of multiple species from gas emission has been performed using direct-absorption spectroscopy. The concentrations of C2H2, CO, CO2 and H2O were determined on the basis of integrated absorbance measured by least-squares fitting a Voigt lineshape to experimental absorption spectra.

We report on recent developments of widely tunable, continuous-wave (CW) laser sources based on difference-frequency generation (DFG) in nonlinear optical materials. The state-of-the-art of CW DFG technology will be reviewed. Applications of the DFG-based laser source to high-resolution molecular spectroscopy and trace gas detection will be presented. New development trends of DFG will be discussed. To cite this article: W. Chen et al., C. R. Physique 8 (2007).

Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development.

Suicide gene therapy with the herpes simplex virus thymidine kinase (HSV-TK) cDNA and ganciclovir can elicit cytotoxicity to transgene-expressing and nonexpressing bystander cells via transfer of ganciclovir phosphates through gap junctions. HeLa cells do not exhibit bystander cytotoxicity, although we showed recently that they transfer low levels of ganciclovir phosphates to bystander cells. Here, we attempted to induce bystander cytotoxicity using hydroxyurea, an inhibitor of ribonucleotide reductase, to decrease the endogenous dGTP pool, which should lessen competition with ganciclovir triphosphate for DNA incorporation. Addition of hydroxyurea to cocultures of HSV-TK-expressing and bystander cells synergistically increased ganciclovir-mediated cytotoxicity to both cell populations while producing primarily an additive effect in cultures of 100% HSV-TK-expressing cells. Whereas HSV-TK-expressing cells in coculture were ∼50-fold less sensitive to ganciclovir compared with cultures of 100% HSV-TK-expressing cells, addition of hydroxyurea restored ganciclovir sensitivity. Quantification of deoxynucleoside triphosphate pools showed that hydroxyurea decreased dGTP pools without significantly affecting ganciclovir triphosphate levels. Although hydroxyurea significantly increased the ganciclovir triphosphate:dGTP value for 12 to 24 hours in HSV-TK-expressing and bystander cells from coculture (1.4- to 4.9-fold), this value was increased for

Development of a continuous-wave tunable fiber laser-based spectrometer for applied spectroscopy is reported. Wide wavelength tunability of an erbium-doped fiber laser (EDFL) was investigated in the near-infrared region of 1543–1601 nm. Continuous mode-hop free fine frequency tuning has been accomplished by temperature tuning in conjunction with mechanical tuning. The overall spectroscopic performance of the EDFL was evaluated in terms of frequency tunability along with its suitability for molecular spectroscopy. High-resolution absorption spectra of acetylene (C2H2) were recorded near 1544 nm with a minimum measurable absorption coefficient of about 3.5×10-7 cm-1/Hz1/2 for direct absorption spectroscopy associated with a 100-m long multipass cell. Detections of C2H2 at different concentration levels were performed as well with high dynamic detection range varying from 100% purity to sub ppmv using cavity ring down spectroscopy. A 3σ-detection-limited minimum detectable concentration (MDC) of 400 ppbv has been obtained by using the transition line Pe(22) of the ν1+ν3+ν5 1(Πg)-ν5 1(Πu) hot band near 1543.92 nm with a detection bandwidth of 2.3 Hz. This corresponds to a minimum detectable absorption coefficient of 6.6×10-11 cm-1/Hz1/2. The sensitivity limit could be further improved by almost one order of magnitude (down to ∼60 ppbv) by use of the Pe(27) line of the ν1+ν3(Σu +)-0(Σg +)combination band near 1543.68 nm.

The combination of cytosine deaminase (CD) and herpes simplex virus thymidine kinase (HSV-TK) suicide gene protocols has resulted in enhanced antitumor activity in cultured tumor cells and animal models. In this study, we show that concurrent addition of prodrugs 5-fluorocytosine (5-FC) and ganciclovir (GCV) was less efficacious than sequential treatment in human DU145 prostate carcinoma cells infected with an adenovirus containing a CD/HSV-TK fusion gene. If cells were incubated for 24 hours with 5-FC followed by a 24-hour GCV treatment, GCV triphosphate levels were 2-fold higher, incorporation of GCV monophosphate into DNA was 2.5-fold higher, and growth inhibition was increased 4-fold compared with simultaneous treatment. As expected, cellular dTTP levels were reduced during the 5-FC preincubation. However, dGTP pools also declined parallel to the dTTP decrease. Similar results were obtained when 5-fluorouracil or 5-fluoro-2′-deoxyuridine was used instead of CD/5-FC. These data allowed us to propose a novel hypothesis for the synergistic interaction between CD/5-FC and HSV-TK/GCV treatments. We suggest that the CD/5-FC–mediated reduction of dTTP results in a concurrent decrease of dGTP due to allosteric regulation of ribonucleotide reductase. Because dGTP is the endogenous competitor of GCV triphosphate, depleted dGTP at the time of GCV addition results in increased GCV in DNA and cell kill. In fact, addition of deoxyguanosine during the 5-FC incubation reverses the dGTP depletion, reduces the amount of GCV monophosphate incorporated into DNA, and prevents the CD/5-FC–mediated enhancement of HSV-TK/GCV cytotoxicity. Understanding this mechanistic interaction may help recognize better strategies for creating more efficacious clinical protocols. (Cancer Res 2006; 66(6): 3230-7)

To improve bystander cell killing with HSV-TK/GCV, we have utilized dFdCyd to reduce endogenous dGTP, which competes with GCVTP for incorporation into DNA. In this study we demonstrate the ability of dFdCyd to enhance GCV-mediated bystander cytotoxicity in cultured SW620 human colon carcinoma cells as well as in a murine xenograft model. In vitro, dFdCyd reduced cellular dGTP levels and produced a fourfold increase in the GCVTP:dGTP ratio. This elevated GCVTP:dGTP ratio resulted in a twofold increase in GCVMP incorporation into DNA in bystander cells cocultured with HSV-TK-expressing cells. The combination of GCV and dFdCyd was determined to be synergistic by isobologram analysis of bystander cytotoxicity. Tumors in mice treated with GCV and dFdCyd exhibited a significant growth delay requiring 40 days to obtain approximately 10 times their initial size compared to tumors in PBS- or single-drug-treated animals, which grew rapidly, increasing to a similar size in just 19 to 24 days. In addition, complete tumor regression was observed only in animals treated with both drugs. Furthermore, dFdCyd alone or in combination with GCV produced no evidence of toxicity or significant weight loss. These data suggest that dFdCyd may improve the clinical efficacy of HSV-TK/GCV gene therapies.

Data center thermal management challenges have been steadily increasing over the past few years due to rack level power density increases resulting from system level compaction. These challenges have been compounded by antiquated environmental control strategies designed for low power density installations and for the worst-case heat dissipation rates in the computer systems. Current data center environmental control strategies are not energy efficient when applied to the highly dynamic, high power density data centers of the future. Current techniques control the computer room air conditioning units (CRACs) based on the return air temperature of the air—typically set near 20°C. Blowers within the CRACs are normally operated at maximum flow rate throughout the operation of the data center unless they are equipped with nonstandard variable frequency drives. At this setting the blowers typically provide significantly more airflow than is required by the equipment racks to prevent recirculation and the subsequent formation of hot spots. This strategy tends to be overly conservative and inefficient. As an example air entering a given system housed in a rack undergoes a temperature rise of 15°C due to the heat added by the system. The return air control strategy strives to keep the entire room at a fixed temperature. Therefore in a typical data center the CRAC supply temperature, and hence the air entering the racks, is 13-15°C and the CRAC return is 20-22°C. At these settings the CRACs can consume almost as much energy as the computer equipment they are cooling [Friedrich, R., Patel, C.D., 2002, “Towards Planetary Scale Computing – Technical Challenges for Next Generation Internet Computing,” THERMES 2002, Santa Fe, NM; The Uptime Institute, “Heat Density Trends in Data Processing, Computer Systems and Telecommunications Equipment,” White Paper issued by The Uptime Institute, 2000.]. Experiments conducted by the authors using these CRAC settings show that nearly 0.7W is consumed by the environmental control system for every 1W of heat dissipated by the computer equipment in the authors’ experimental facility indicating that the energy efficiency of standard data center environmental control systems is poor. This study examines several opportunities for improving thermal management and energy performance of data centers with automatic control. Experimental results are presented that demonstrate how simple, modular control strategies can be implemented. Furthermore, experimental data is presented that show it is possible to improve the energy performance of a data center by up to 70% over current standards while maintaining proper thermal management conditions.

Three case reports expand the clinical spectrum of HPeV-3 infections and highlight the need to characterize this new pathogen., A third serotype of human parechovirus (HPeV) has been recently isolated from stool specimens of a young Japanese child with transient paralysis. We report 3 additional cases of neonatal sepsis caused by HPeV-3 in the fall of 2001 in Canadian infants 7–27 days old. All children were hospitalized with high fever, erythematous rash, and tachypnea for a median of 5 days. The viruses isolated from nasopharyngeal aspirates grew slowly on tertiary monkey kidney cells and were successfully passaged on Vero cells. The predicted amino acid identity of the VP0-VP3-VP1 region of the three viruses was 74.6%–74.8%, 73.4%–73.6%, and 97.0%–97.1% when compared to HPeV-1, -2, and –3 prototype strains, respectively. Although different, our isolates were closely related; amino acid identity was 99.6%–100% for the last 3 proteins.

This study, performed using semen samples from 10 men, investigated the relationship between sperm protein tyrosine phosphorylation and acrosomal status in conditions supporting in vitro capacitation. Percoll-selected spermatozoa (cells from the 95% fraction) were incubated for 3 h at 37 degrees C under an atmosphere of 5% CO2 in air, in a polyvinyl alcohol (1 mg ml(-1)) containing Biggers-Whitten-Whittingham's medium, nonsupplemented or supplemented with either bovine serum albumin (BSA; fatty acid free, 3 mg ml(-1)) or 2-hydroxy-propyl-beta-cyclodextrin (2-OH-p-beta-CD; 0.5, 1, 2 mmol l(-1)). Sperm suspension in each medium was split into two aliquots. The first was used to evaluate the acrosomal status by staining with the fluorescein isothiocyanate Pisum sativum agglutinin after induction of the acrosome reaction (AR) for 45 min with 10 micromol l(-1) of A23187 calcium ionophore. The second aliquot was used for sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting, followed by a densitometric analysis. Compared with the nonsupplemented medium, BSA- or 2-OH-p-beta-CD-supplementation induced an increase in both the percentage of live acrosome-reacted sperm and the tyrosine phosphorylation intensity of the main phosphorylated 107 kDa protein. A correlation between the percentage of live acrosome-reacted sperm and the 107-kDa protein phosphotyrosine intensity was observed. Therefore, the 107 kDa protein-phosphotyrosine level measurement would bring additional information to conventional semen parameters in the assessment of the human sperm functionality.

Objective. Although universal immunization against Bordetella pertussis (whooping cough) infection has resulted in dramatic reductions in the incidence of pertussis, outbreaks continue to occur in countries with excellent vaccine coverage. Treatment of infection may ameliorate symptom severity during the catarrhal phase of pertussis but has no effect on established paroxysms, emesis, or apnea if given during the paroxysmal or convalescent phases. Erythromycin, recommended for treatment of pertussis to prevent transmission of infection, is poorly tolerated because of gastrointestinal side effects. We compared the safety and efficacy of erythromycin with azithromycin for treatment of pertussis in a large, randomized, controlled trial that enrolled children from primary care practices in 1 American and 11 Canadian urban centers. Methods. Children who were 6 months to 16 years of age and had cough illness that was suspected to be or was culture confirmed as pertussis were randomized to azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2–5 as a single dose) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) with stratification by center. The primary outcome measure was bacteriologic cure of infection as determined by cultures of nasopharyngeal aspirates. Culture-positive participants had a second aspirate collected at the end of therapy (days 5–7 for azithromycin, days 10–12 for erythromycin) and 1 week after therapy. Bacteriologic cure was defined as negative cultures at the end of therapy. Bacteriologic relapse was defined as a positive culture 1 week after completion of therapy and after a negative end-of-therapy culture. Secondary outcomes were pertussis diagnosed by serology and polymerase chain reaction (PCR), treatment-associated adverse events, compliance, and presence of clinical symptoms at the end of the treatment course. Serology was performed using standard enzyme-linked immunosorbent assay methods. A participant was considered to have pertussis when the PCR was positive or a 4-fold increase in pertussis toxin antibody between baseline and follow-up visits was observed. PCR was performed using a 1046-bp ClaI DNA fragment from B pertussis. Adverse events (nausea, vomiting, diarrhea, any gastrointestinal complaint, or other) were determined by a parent-completed diary that was reviewed with study personnel during study visits. Compliance was measured by review of the parent medication diary during study visits and observation of medication containers by the pharmacist at study completion. Symptoms were determined by history collected by study personnel at enrollment and subsequently from the diary. The design of the study was an equivalence trial, aimed at demonstrating that the bacteriologic failure rates with the 2 therapies did not differ by >8%. For the safety analysis, all participants who received at least 1 dose of study drug were included. In the per-protocol efficacy analysis, all culture-positive participants with end-of-treatment cultures were considered. Results. A total of 477 children were enrolled and randomly assigned to either azithromycin (n = 239) or erythromycin (n = 238). Of these children, 114 (24%) grew B pertussis from nasopharyngeal specimens (azithromycin group: 58 of 239 [24%]; erythromycin group: 56 of 238 [23%]); these children composed the efficacy cohort for the per-protocol and intention-to-treat analyses. Serology and PCR added 52 children to the number considered to have pertussis for a total of 35% (166 of 477) of all children who presented with cough illness. In the safety analysis (antibiotic side effects, compliance) and comparison of cough symptoms after treatment, all randomized children are reported in their assigned treatment group. At end of therapy, bacterial eradication was demonstrated in all 53 patients in the azithromycin group and all 53 patients in the erythromycin group with follow-up cultures available (eradication 100%; 95% confidence interval [CI]: 93.3–100). No bacterial recurrence was demonstrated in children with 1 week posttreatment nasopharyngeal cultures available (51 and 53 participants in the azithromycin and erythromycin arms, respectively [0%, 95% CI: 0–7.0; and 0%, 95% CI: 0–6.7]). No serious adverse events attributable to study drug were observed. Gastrointestinal adverse events were reported less frequently in azithromycin (18.8%; 45 of 239) than in erythromycin estolate (41.2%; 98 of 238) recipients (90% CI on difference: −29.0% to −15.7%) as a result of less nausea (2.9% vs 8.4%; 95% CI: −8.9% to −2.0%), less vomiting (5.0% vs 13.0%; 95% CI: −4.9% to −1.4%), and less diarrhea (7.1% vs 11.8%; 95% CI: −9.0% to −0.3%). Children who were randomized to azithromycin were much more likely to have complied with antimicrobial therapy over the treatment period. In the azithromycin group, 90% of children took 100% of prescribed doses, whereas only 55% of children in the erythromycin group took 100% of prescribed doses. Conclusions. In this large, multicenter, randomized trial, we found that azithromycin is as effective as erythromycin estolate for the treatment of pertussis in children. Gastrointestinal adverse events were much more common with erythromycin treatment than azithromycin. Compliance with therapy was markedly better with azithromycin than with erythromycin in this study.

Cryopreservation-induced stress may result in membrane injury with consequent decrease of sperm motility and fertilizing capacity. This study has investigated the relationship between human spermatozoa tolerance to cryopreservation and the loss of plasma membrane asymmetry, especially translocation of phosphatidylserine (PS) from the inner to the outer leaflet. The prospective study was performed on semen samples from 31 men. Conventional characteristics of 20 semen were analysed, before and after cryopreservation as well as externalization of PS assessed by annexin V-staining in combination with the propidium iodide which stains dead cells. The fertilizing capacity was evaluated by a zona free hamster egg penetration test in 11 freeze/thaw spermatozoa samples. The percentages of vital annexin V-negative and annexin V-positive spermatozoa in post-thaw samples were significantly lower than in pre-freeze ones (10 +/- 3 vs. 25 +/- 5% and 22 +/- 3 vs. 34 +/- 4% respectively), while the percentages of dead spermatozoa annexin V-negative and annexin V-positive had increased (42 +/- 4 vs. 23 +/- 4% and 23 +/- 4 vs. 16 +/- 2% respectively). The percentages of progressive and total motile spermatozoa were significantly correlated with the percentage of vital annexin V-negative spermatozoa before as well as after cryopreservation. Furthermore, recovery of motile spermatozoa after freeze/thaw was strongly correlated (p < 0.002) with the proportion of vital annexin V-negative spermatozoa in fresh semen. The percentage of penetration of zona-free hamster eggs was correlated (p < 0.02) with the percentage of live annexin V-negative cryopreserved spermatozoa capacitated for 3 h. These findings provide evidence that annexinV-binding staining in combination with PI brings additional information to predict the outcome of cryopreserved ejaculated sperm and may be used as a novel and reliable marker to study the freeze/thaw process.

L’interet et la faisabilite de la cryoconservation des spermatozoides testiculaires humains sont maintenant bien demontres. Toutefois, la realisation de la congelation de ces spermatozoides reste empirique, elle est basee essentiellement sur les techniques utilisees pour les spermatozoides de l’ejaculât. Les spermatozoides testiculaires sont consideres comme des gametes encore «immatures» et sont toujours retrouves en quantite limitee. Une meilleure connaissance de leurs caracteristiques cryobiologiques contribuerait a mieux definir le type d’echantillon a congeler (tissu, suspension cellulaire contenant des spermatozoides.…), a faire evoluer les processus de congelation/decongelation et la nature des milieux cryoprotecteurs et a adapter les conditions de stockage. Compte tenu des caracteristiques fonctionnelles de ces spermatozoides et du fait qu’ils sont utilises exclusivement en ICSI, de nouveaux tests d’evaluation de la resistance a la congelation bases notamment sur leur qualite nucleaire devraient etre developpes.

A continuous-wave (cw) mid-infrared spectrometer based on laser difference frequency generation (DFG) in gallium selenide (GaSe) crystal was developed for quantitative analysis of heavy molecules. The spectrometer and its spectroscopic applications to study of molecular line parameters (such as line strength, pressure broadening coefficients) are presented. The first measurement, to our knowledge, of the self and air broadening coefficients for the ν7 8 2,7 ← 8 1,7 ethylene (C2H4) transition line at 958.1531 cm−1 is reported.

The Middle Triassic flora of the Fremouw Formation in the central Transantarctic Mountains consists of conifers, cycads, ferns, pteridosperms, and sphenophytes. Stems with an unusual anatomy have been discovered within silicified peat from the same locality. The diameters of the stems range from 1.4 to 1.7 cm; the longest specimen is approximately 12 cm. In transverse section the vascular system consists of segments that occur as single traces or are connected in the center and anastomose at varying levels within the stem. Each segment contains a bifacial vascular cambium. Secondary tissues of each segment surround a central area of parenchyma and small tracheids presumed to represent primary xylem. Surrounding the stem is a periderm. Traces are produced near the periphery of the axis and consist of radially arranged secondary xylem and a thick periderm. The absence of leaves and reproductive organs leads to uncertain phylogenetic relationships. We are unaware of any Triassic plants with this type of vascular tissue organization, and those plants with a similar type of arrangement occur only in the Devonian and Carboniferous. Possible phylogenetic affinities with the Cladoxylales and Lycophyta are examined, but the anatomical differences, along with stratigraphic age, preclude formal assignment to any known taxon at this time. Therefore, we have assigned it to a new taxon: Hapsidoxylon terpsichorum gen. et sp. nov.

Gap junctional intercellular communication and expression of gap junction proteins (connexins) are decreased frequently in neoplastic cells including human ovarian carcinoma cells. In order to test the hypothesis that these changes contribute to the neoplastic phenotype of ovarian carcinoma cells, we transfected human ovarian carcinoma SKOV-3 cells with connexin43. Stable, connexin43-expressing transfectants were characterized for cell proliferation in vitro in normal, low-serum, and serum-free culture medium, for tumorigenicity in nude mice, and for sensitivity to adriamycin in vitro. Transfected clones expressed higher levels of connexin43 and gap junctional intercellular communication, reduced proliferation and greater dependence upon serum for growth in vitro, decreased tumor formation, increased sensitivity to adriamycin, and reduced expression of p-glycoprotein. These data suggest that gap junctional intercellular communication and/or connexin43 expression suppresses the neoplastic phenotype of ovarian carcinoma cells and their downregulation is involved in neoplastic transformation of ovarian epithelial cells. The increased sensitivity to adriamycin and elevated expression of p-glycoprotein by the transfected cells also suggest that gap junctional intercellular communication and connexin43 expression are involved in drug sensitivity and might be manipulated to enhance the clinical response.

We have previously demonstrated with several cell lines in vitro that hydroxyurea (HU) synergistically enhances ganciclovir (GCV)-mediated cytotoxicity in bystander cells. In this study, we evaluated the role of DNA synthesis inhibition on enhanced bystander killing and assessed whether addition of HU would improve the efficacy of the HSV-TK/GCV system in vivo. Compared with GCV treatment alone, addition of HU resulted in increased DNA synthesis inhibition and delayed progression through S phase following removal of drug. In a xenograft tumor model, 1:10 and 1:1 mixtures of HSVtk- and LacZ-expressing SW620 cells were injected s.c. in the flanks of nude mice and treated i.p. (100 mg/kg GCV, 1500 mg/kg HU) daily for 5 days. Tumors from mice treated with GCV alone grew rapidly and increased to 10 times their initial size in 15.7 +/- 1.8 and 16.0 +/- 0.9 days for 1:10 and 1:1 mixtures, respectively. However, when both GCV and HU were administered in combination, a single complete tumor regression was observed in both the 1:10 and 1:1 groups. In the remaining mice treated with GCV/HU, it took 23.2 +/- 2.1 (1:10) and 26.4 +/- 3.8 days (1:1) to obtain a similar 10-fold increase in tumor size.

Ganciclovir (GCV) is widely used as a prodrug for selective activation in tumor cells expressing herpes simplex virus thymidine kinase (HSV-TK) because of its ability to induce multi-log cytotoxicity to HSV-TK-expressing as well as nonexpressing bystander cells. We now report that another substrate for HSV-TK, D-carbocyclic 2'-deoxyguanosine (CdG), induces multi-log cytotoxicity in HSV-TK-expressing and bystander cells at concentrationsor=3 microM. We have compared the cytotoxicity and cell cycle effects of CdG to that observed with GCV in two human tumor cell lines. The results demonstrated that cytotoxicity of CdG was similar to that of GCV in both U251 glioblastoma and SW620 colon carcinoma cells that stably expressed HSV-TK. In addition, CdG induced a potent bystander effect in both cell types in co-cultures consisting of HSV-TK-expressing and nonexpressing bystander (lacZ-expressing) cells at ratios of 50:50 or 10:90. Selectivity for HSV-TK-expressing compared to lacZ-expressing cells was similar for CdG and GCV in the U251 cells, however CdG was less selective than GCV in the SW620 cell lines. Despite their ability to induce multi-log cytotoxicity at similar concentrations, CdG and GCV exhibited differential effects on cell cycle progression. Cells incubated with 1 microM CdG for 24 hr accumulated in S-phase and G(2)/M after drug washout, and the majority of cells died prior to cell division. This contrasts with the delayed effects of 1 microM GCV that were not evident until after cell division when cells attempted S-phase for the second time. Thus, CdG is a potent cytotoxic agent that merits further investigation to determine whether it will be therapeutically effective in enzyme-prodrug therapy with HSV-TK.

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.

We investigate a new experimental method for detecting molecules from the ultraviolet to the near infrared range using ultrashort laser pulses. Two types of sources are used: a white light continuum generated by 200khz Ti: Sapphire regenerative amplifier system, and a near-gaussian femtosecond pulse (100 fs) generated by an optical parametric amplifier and tunable from 0.45 to 2.4 μm. Up to now, this technique has only been performed in the visible domain. Both broadband sources allow the detection of the oxygen and the water vapor bands. Moreover, a new extraction method has been implemented, which provides the molecules' concentration by using a nonlinear fit technique.

OBJECTIVES: Given the improved efficacy of the nasal live-attenuated influenza virus vaccine (LAIV) compared with the injectable vaccine in children, we aimed to determine its safety in individuals with cystic fibrosis (CF). METHODS: A cohort of 168 study participants, aged 2 to 18 years with CF, vaccinated with LAIV between October 1, 2012, and January 30, 2013, was followed prospectively for 56 days after initial vaccination in 3 pediatric CF clinics across the province of Quebec. Days 0 to 28 post-LAIV were considered the at-risk period for all outcomes of interest, and days 29 to 56 post-LAIV were considered the non–at-risk period. Incident respiratory deteriorations were defined as an unscheduled medical visit, hospitalization, or a new course of oral antibiotics for respiratory complaints. Using a self-controlled design, incidence rate ratios (IRR) were used to compare at-risk and non–at-risk periods. RESULTS: Comparing at-risk to non–at-risk periods, there was no significant increase in the rate of incident respiratory deteriorations (IRR, 0.72; 95% confidence interval, 0.11–4.27) or all-cause hospitalizations (IRR, 1.16; 95% confidence interval, 0.30–4.81). A greater proportion of participants reported experiencing at least 1 minor respiratory and/or systemic adverse event after immunization during the at-risk period compared with the non–at-risk period (77% vs 54%, respectively). During the first week after LAIV, 13 of 168 (8%) children reported some wheezing, with the vast majority, 9 of 13 (69%), on the day of vaccination. CONCLUSIONS: There was no increased risk of respiratory deterioration or all-cause hospitalization associated with LAIV in our study population. LAIV seems well tolerated in children and adolescents with CF.

In this work, we examined whether spermatozoa (spz) from normospermic fertile patients and selected by a swim-up (S-U) procedure had a particular membrane fluidity related to their maturity and their lipid content as compared with the sperm cells from the whole ejaculate (total sperm). Swim-up selected sperm had a reduced cytoplasmic space as revealed by a lower creatine kinase (CK) activity compared with total sperm (2 +/- 1 vs. 12 +/- 5 mUI/10(7) spz, p < 0.05). The cholesterol (Chol) and total phospholipid (PL) contents were significantly lower in S-U selected sperm than in total sperm (0.72 +/- 0.08 vs. 1.20 +/- 0.30 nmol/10(6) spz for Chol and 1.77 +/- 0.17 vs. 2.78 +/- 0.50 nmol/10(6) spz for PL, p < 0.05) and such a decrease was observed for the three major membrane PL: phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphingomyelin (SM). However, these decreases were not associated with a change in either Chol/PL or PC/(PC + PE) molar ratios. Membrane fluidity estimated by fluorescence polarization remained comparable between the S-U sperm fraction and total sperm (fluorescence polarization anisotropy, r, which is inversely proportional to the fluidity: 0.235 +/- 0.006 vs. 0.230 +/- 0.005). The sperm membrane fluidity obtained in normospermic patients was compared with abnormospermic ones (oligoasthenoteratospermia). In abnormospermic patients, the membrane fluidity was decreased in migrated spermatozoa compared with total sperm (anisotropy: 0.210 +/- 0.010 vs. 0.250 +/- 0.013, p < 0.01). Our data suggest that the S-U method selected a subpopulation of mature spermatozoa characterised by a low content of Chol and PL, likely related to a reduced membrane area. The fact that Chol/PL and PC/(PC + PE) molar ratios were unchanged shows a maintenance of the membrane quality. This was confirmed by the fluorescence anisotropy measurement showing no difference in plasma membrane fluidity between S-U selected sperm and total sperm. In abnormal semen the migrated spermatozoa had a lower fluidity compared with total sperm suggesting a defective sperm function. These results bring new elements characterizing the S-U selected spermatozoa.

A simple, rapid and accurate method to separate and quantify cholesterol, desmosterol and cholesterol sulfate in human spermatozoa and seminal plasma (SP) is described. This high-performance liquid chromatographic procedure is based on reversed-phase chromatography on a Inertsil ODS2 5 microm silica column with a binary gradient of mixtures of chloroform-methanol and chloroform-methanol-water as the mobile phase at a flow-rate of 0.25 ml/min. Sterols are separated with good resolution and high reproducibility. The eluted sterols are quantified using a light-scattering (mass) detector. As little as 64, 64 and 68 pmol of cholesterol, desmosterol and cholesterol sulfate, respectively, can be quantified under these conditions. Cholesterol is the predominant sterol both in spermatozoa (107+/-7 nmol/10(8) spermatozoa) and SP (0.83+/-0.10 micromol/ml) whereas the concentrations of desmosterol were 38+/-6 nmol/10(8) in spermatozoa and 0.18+/-0.02 micromol/ml in SP. Cholesterol sulfate represents about 6% of total cholesterol in the spermatozoa and SP. In conclusion, this method offers interesting perspectives for the quantitative analysis of these sterols not only in semen, but also in other biological samples.

Les prostasomes sont des vesicules lipidiques particulieres secretees par la prostate humainne et retrouvees dans le sperme. Actuellement, aucune action specifique ne leur a ete attribuee. Cependant, les prostasomes semblent exercer un effet a differents niveaux. Par exemple, les prostasomes sont benefiques pour la mobilite des spermatozoidesin-vitro et participent a l’immunomodulation exercee par le liquide seminal. La production de derives actifs de l’oxygene (DAO) dans le sperme humain joue un role sur les capacites fonctionnelles des spermatozoides. La production de quantites faibles et controlees de DAO par les spermatozoides semble necessaire a l’acquisition de leur capacites fonctionnelles. Par contre, la presence de leucocytes dans le sperme, associee a une forte production de DAO, peut se reveler nefaste pour les spermatozoides. Apres avoir aborde, sous forme d’une revue bibliographique, les caracteristiques structurales et fonctionnelles des prostasomes et le role des DAO dans le sperme humain, nous rapportons nos resultats concernant les effets des prostasomes sur la production des DAO et les consequences sur les spermatozoides. Nous avons mis en evidence une fonction antioxydante des prostasomes dans le sperme humain. Elle s’exerce a la fois sur les polynucleaires neutrophiles et sur les spermatozoides. Le mode d’action des prostasomes est particulier puisqu’ils interviennent sur la production des DAO, en agissant notamment au niveau des membranes des polynucleaires neutrophiles. Ils entrainent une diminution de l’activite NADPH-oxydase de ces cellules associee a une rigidification de leur membrane plasmique. Au niveau des spermatozoides, les prostasomes protegent leurs capacites fonctionnelles lors d’un stress oxydant cree par la presence de NADPH dans le milieu.

Au cours de ces dernieres annees les tentatives d’ICSI realisees avec des spermatozoides testiculaires se sont considerablement accrues. Cependant, l’une des difficultes techniques tient au fait que la mobilite des spermatozoides est extremement reduite. Un accroissement de la mobilite avait ete observe apres une incubation des prelevements testiculaires pendant quelques heures. Dans l’optique d’augmenter les chances de succes, une culture in vitro des spermatozoides, prealable a l’ICSI, a ete envisagee. Nous rapportons ici la revue de la litterature sur ce sujet. Dans les azoospermies obstructives, la culture in vitro presente peu d’interet puisque, excepte une eventuelle “maturation” des spermatozoides pendant cette periode, un pourcentage appreciable de spermatozoides mobiles est souvent observe rapidement apres le traitement de la biopsie. Dans les azoospermies non obstructives la culture in vitro parait justifiee, puisque lorsque l’on retrouve des spermatozoides dans la biopsie, ils sont generalement immobiles. Cependant, la plupart des auteurs s’accordent a reconnaitre que les resultats restent aleatoires: au terme de la culture, soit il existe un gain de mobilite, soit au contraire la plupart des spermatozoides sont morts. Quelque soit le type d’azoospermie, les meilleurs resultats sont obtenus apres 3–4 jours de culture. La supplementation des milieux de culture avec de la FSH recombinante s’avere aussi efficace. La culture in vitro peut etre associee a la congelation des spermatozoides et la sequence culture in vitro/congelation donnerait de meilleurs resultats que la sequence congelation/culture in vitro. Les quelques travaux sur l’utilisation en ICSI des spermatozoides maintenus en culture in vitro pendant 1 a 2 jours rapportent des resultats satisfaisants en terme de taux de fecondation et de grossesse. La culture in vitro de spermatozoides testiculaires peut constituer une voie de recherche interessante pour ameliorer les resultats en ICSI, dans les cas ou la quantite de spermatozoides retrouvee et/ou leur mobilite sont tres faibles. De plus, elle nous parait etre un bon modele d’etude des mecanismes d’acquisition de la mobilite des spermatozoides.

Le Diuron est un herbicide appartenant a la famille des halogenophenyluree. Un test de toxicite base sur l’inhibition de la bioluminescence d’une bacterie marineVibrio fischeri, comme indicateur de toxicite a montre que les produits de bio- ou photo-transformation sont plus toxiques que le Diuron lui-meme. Tous ces composes sont des molecules tres lipophiles et une membrane cellulaire riche en lipides comme celle du spermatozoide pourrait etre une cible privilegiee pour leur interaction avec la cellule. Des etudes sont en cours dans notre laboratoire afin d’evaluer les effetsin vitro du Diuron et de l’un de ses produits de transformation, la 3,4-dichloroaniline (3,4-DCA) (obtenu par elimination de la fonction uree) sur les proprietes structurales et fonctionnelles du spermatozoide humain. Les etudes sont realisees sur des spermatozoides provenant de spermes normaux (criteres de l’OMS), purifies sur gradient discontinu de Percoll. Trois millions de spermatozoides/ml sont incubes dans un milieu synthetique de Earle depourvu de rouge de phenol, supplemente par 7,5% de serum humain decomplemente pendant 24 heures, a temperature ambiante, en presence de Diuron ou de 3,4-DCA (0,1; 1; 5 mM) dans un volume final de 250 μl. Nos premiers resultats mettent en evidence une diminution de la vitalite et de la mobilite des spermatozoides apres 24 heures d’incubation en presence de 5 mM de Diuron. L’anisotropie (inversement proportionnelle a la fluidite membranaire) mesuree par polarisation de fluorescence en utilisant une sonde lipophile, le 1,6-Diphenyl-1,3,5-Hexatriene est aussi diminuee. La 3,4-DCA entraine des effets plus rapides et plus marques que le Diuron. Tous les spermatozoides sont “morts” apres 30 minutes ou 24 heures d’incubation, en presence respectivement de 5 mM et 1 mM de 3,4-DCA. Aux concentrations utilisees, ces molecules s’averent plus toxiques pour le spermatozoide et cet effet semblerait etre lie a une atteinte membranaire. Cette etude preliminaire suggere que des tests puissent etre developpes a partir des spermatozoides humains pour evaluer la toxicite de certains pesticides.

A laser-based infrared spectrometer was developed for use in high-resolution spectroscopic analysis of trace gases in the atmosphere. Continuous wave, broadly tunable coherent infrared radiation was generated from 8 to 19 μm in a gallium selenide crystal by laser difference-frequency mixing. Measurements of acetylene trace concentrations using laser absorption spectroscopy are reported. The measurements have been performed by using the P(21), Q(11), and R(9) lines of the ν5 band, respectively, in order to investigate optimal detection conditions: a trade-off choice between higher line absorption strength for sensitive detection and better spectral discrimination from lines overlapping for open path trace-gas monitoring applications. Minimum detectable concentrations are compared under different experimental conditions. The ν5 R(9) line seems to be close to optimum in terms of absorption strength and freedom from spectral interference for spectroscopic detection of acetylene trace concentration at atmospheric pressure.

Microdeletions of the long arm of the Y chromosome (Yq) are a common cause of male infertility. Since large structural rearrangements of the Y chromosome are commonly associated with a 45,XO/46,XY chromosomal mosaicism, we studied whether submicroscopic Yq deletions could also be associated with the development of 45,XO cell lines. We studied blood samples from 14 infertile men carrying a Yq microdeletion as revealed by polymerase chain reaction (PCR). Patients were divided into two groups: group 1 (n = 6), in which karyotype analysis demonstrated a 45,X/46,XY mosaicism, and group 2 (n = 8) with apparently a normal 46,XY karyotype. 45,XO cells were identified by fluorescence in-situ hybridization (FISH) using X and Y centromeric probes. Lymphocytes from 11 fertile men were studied as controls. In addition, sperm cells were studied in three oligozoospermic patients in group 2. Our results showed that large and submicroscopic Yq deletions were associated with significantly increased percentages of 45,XO cells in lymphocytes and of sperm cells nullisomic for gonosomes, especially for the Y chromosome. Moreover, two isodicentric Y chromosomes, classified as normal by cytogenetic methods, were detected. Therefore, Yq microdeletions may be associated with Y chromosomal instability leading to the formation of 45,XO cell lines.

An international multi-tokamak profile database has been assembled, constituting a representative set of reference tokamak discharges for the purpose of testing local transport models against well documented data. In particular, it will allow one to measure the accuracy with which the models can reproduce experiments and draw confidence intervals for the predictions of the models outside the range covered in the database. This database is now available to the fusion community and may be accessed by anonymous ftp to iterphys.naka.go.jp; the purpose of this article is to describe the structure of the database and the discharges contributing to it so that all can take full advantage of this resource. Thus, after an introductory general discussion of the database, there is a more detailed description of its structure, with listings of variables emphasized and how to access the database. There is then a brief description of each contributing tokamak and information on the type of discharges available from that tokamak. This is followed by a more quantitative description of the data, giving the ranges of dimensional and dimensionless variables available. Some typical modelling results to illustrate the use of the database are given in the conclusion.

Semen cryopreservation is an important procedure in the treatment of human infertility. However, the ability of spermatozoa to survive freeze/thaw processes varies between patients. Cryopreservation-induced stress may result in membrane injury with consequent loss of sperm motility and viability. We investigated the relationship between the physico-chemical state of the human sperm membranes and their tolerance to cryopreservation. Conventional characteristics of 20 semen samples were analysed before and after cryopreservation as well as their membrane fluidity assessed by measuring the fluorescence polarization anisotropy, which is inversely proportional to the fluidity. Correlation between fluidity and post-thaw recoveries of motile and viable spermatozoa were examined. Results showed that membrane anisotropy markedly varies between patients. In cryopreserved spermatozoa, anisotropy values were significantly higher than in fresh spermatozoa. Furthermore, recovery of motile and viable spermatozoa after freeze/thaw was strongly correlated with anisotropy of fresh spermatozoa (P < 0.05). The higher the membrane fluidity was before freezing, the better was the response of spermatozoa to cryopreservation. The results indicate that the freeze/thaw process results in a rigidifying effect on the sperm membrane and suggest that sperm adaptability to freeze/thaw-induced stress could be dependent on their initial membrane fluidity. The latter finding has practical implications for predicting the response of spermatozoa following freezing and thawing and for improving the recovery of viable spermatozoa.

We report the cytologic features of 15 cases of angiosarcoma from various sites and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid specimen. Six were initial diagnoses with histologic confirmation; an additional case in the liver was an initial diagnosis without tissue confirmation. One case represented lymph node metastasis from a primary prostatic epithelioid angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology or histology specimen. The aspirates varied in cellularity, and the degree of nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma of the prostate to highly pleomorphic in a lymph node metastasis from a facial cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well-formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic lumens were variably present. The background was bloody in all specimens, with necrosis in rare cases. This cytologic series emphasizes that the cytologic features are heterogeneous but that the diagnosis can be suggested by fine-needle aspiration (FNA) when vasoformative features are present. The diagnosis can be made conclusively by FNA with immunocytochemical confirmation of endothelial differentiation.

The plasma performance in two design options of the reduced-technical objectives/reduced cost (RTO/RC) ITER, i.e. IAM (intermediate aspect ratio machine) and LAM (low aspect ratio machine) is analysed. It is shown that Q = Pfus/Paux~10 can be obtained in both options at inductively driven ELMy H-mode operation. The operation domain in LAM is found to be marginally larger than that in IAM. The non-inductive operation with Q≈5 will be possible in both machines, provided a large amount of power with a high current drive efficiency is applied, or substantial improvement of the energy confinement time relative to the ELMy H-mode (HH = 1.2-1.4) is obtained. The required values of HH and βN are marginally smaller in IAM. The IAM-like machine, ITER-FEAT (fusion energy advanced tokamak), proposed for a detailed engineering design is discussed in brief.

Features incorporated in the design of the International Thermonuclear Experimental Reactor (ITER) tokamak and its ancillary and plasma diagnostic systems that facilitate operation and control of ignited and/or high?Q DT plasmas are presented. Control methods based upon straightforward extrapolation of techniques employed in the present generation of tokamaks are found to be adequate and effective for ITER plasma control with fusion powers of up to 1.5?GW and burn durations of ? 1000?s. Examples of simulations of key plasma control functions, including plasma magnetic configuration control and fusion burn (power) control, are given. The prospects for the creation and control of steady state plasmas sustained by non-inductive current drive and bootstrap current are also discussed.

High precision index measurements (Δn/n ≤ 10-5) have been recently achieved on an AgGaS2 crystal using a spectral interferometry technique with a polarized white-light continuum. Up to now, these measurements are limited to the visible and near-infrared range, the most dispersive domain. We investigate the possibility to extend the technique to far infrared index measurements. We demonstrate a criterion depending only on group velocity dispersion and crystal thickness for planning future experiments.

White-light spectral interferometry appears an excellent tool for precise determination of indices, and has already been successfully applied to different isotropic or weakly dispersive materials such as glass or rhodamine films. In this paper, we extend the spectral method to the measurement of anisotropic media with strong dispersion. The method is discussed below and allows an accuracy of the order of 10-5 on the principal indices of a birefringent silver thiogallate (AgGaS2) crystal.

A new property of a one-dimensional periodic structure — amplification of the sum-frequency signal arising under the simultaneous action of two laser pulses on this structure with radiation frequencies corresponding to the edges of the fixed Bragg band gap — is experimentally observed and described.

Objective.We wished to compare outcomes of respiratory syncytial virus (RSV) infection in children with bronchopulmonary dysplasia (BPD) with those with other pulmonary disorders: cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmona

Continuous-wave infrared generation based on nonlinear frequency conversion is described. Broadly tunable infrared radiation was generated from 4 to 19 μm by difference-frequency mixing of two optical lasers in AgGaS2 or GaSe crystal. Related techniques encountered in power conversion efficiency, synchronously phase-matched infrared wavelength scan, extension of phase-matchable infrared spectral coverage, power-balanced detection, etc. are discussed. Applications of this nonlinear generation source to spectroscopy, as well as to environmental air monitoring are presented.