Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.

The immunosuppressant rapamycin (RAPA) inhibits mammalian target of rapamycin (mTOR) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD), although the cellular targets of RAPA treatment are not well defined. Allogeneic T cells are the main drivers of GVHD, while immunoregulatory myeloid-derived suppressor cells (MDSCs) were recently identified as potent disease inhibitors. In this study, we analyzed whether RAPA prevents the deleterious effects of allogeneic T cells or supports the immunosuppressive functions of MDSCs in a BMT model with major histocompatibility complex (MHC) classes I and II disparities. RAPA treatment efficiently attenuated clinical and histological GVHD and strongly decreased disease-induced mortality. Although splenocyte numbers increased during RAPA treatment, the ratio of effector T cells to MDSCs was unaltered. However, RAPA treatment induced massive changes in the genomic landscape of MDSCs preferentially up-regulating genes responsible for uptake or signal transduction of lipopeptides and lipoproteins. Most importantly, MDSCs from RAPA-treated mice exhibited increased immunosuppressive potential, which was primarily inducible nitric oxide synthase (iNOS)-dependent. Surprisingly, RAPA treatment had no impact on the genomic landscape of T cells, which was reflected by unchanged expression of activation and exhaustion markers and cytokine profiles in T cells from RAPA-treated and untreated mice. Similarly, T cell cytotoxicity and the graft-versus-tumor effect were maintained as co-transplanted tumor cells were efficiently eradicated, indicating that the immunosuppressant RAPA might be an attractive approach to strengthen the immunosuppressive function of MDSCs without affecting T cell immunity.

Relations among maternal physical activity during pregnancy and child body composition.

OBJECTIVE: Physical activity (PA) during pregnancy is associated with lower neonatal fat mass, but associations with child body composition are mixed. The purpose of this study was to examine associations between trimester-specific pregnancy PA and child body composition at 4 years. METHODS: Participants of the Minnesota Infant Nutrition, Neurodevelopment, and Obesity Study were asked to recall participation in any moderate or vigorous PA in the first (T1), second (T2) and third (T3) trimesters at about 5 years postpartum. Child fat mass and fat-free mass were measured via air displacement plethysmography at 2 weeks, 3 months and 4 years of age. Multivariate linear regression was used for analyses. RESULTS: Of 51 possible participants, 37 recalled pregnancy PA. Any vigorous PA in T3 was associated with lower child fat mass at 4 years (adjß = -1.077, p < 0.05). CONCLUSION: Late pregnancy PA may have lasting benefits for child body composition. Replication of these findings is needed in a larger sample with prospective measures.

Experimental Evidence for Transverse Wobbling in

New rotational bands built on the ν(h_{11/2}) configuration have been identified in ^{105}Pd. Two bands built on this configuration show the characteristics of transverse wobbling: the ΔI=1 transitions between them have a predominant E2 component and the wobbling energy decreases with increasing spin. The properties of the observed wobbling bands are in good agreement with theoretical results obtained using constrained triaxial covariant density functional theory and quantum particle rotor model calculations. This provides the first experimental evidence for transverse wobbling bands based on a one-neutron configuration, and also represents the first observation of wobbling motion in the A∼100 mass region.

Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age.

OBJECTIVE: Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants. STUDY DESIGN: A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression. RESULTS: Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P⩽0.001), shorter (57.9 vs 60.9 cm, P⩽0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P⩽0.05) and were leaner (percent body fat 15.0 vs 23.8, P⩽0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors. CONCLUSIONS: Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development.

Evidence for a spin-aligned neutron-proton paired phase from the level structure of (92)Pd.

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

Fast electron transport and induced heating in solid targets from rear-side interferometry imaging.

Fast adiabatic plasma heating of a thin solid target irradiated by a high intensity laser has been observed by an optical fast interferometry diagnostic. It is driven by the hot electron current induced by the laser plasma interaction at the front side of the target. Radial and longitudinal temperature profiles are calculated to reproduce the observed rear-side plasma expansion. The main parameters of the suprathermal electrons (number, temperature, and divergence) have been deduced from these observations.

High flux of relativistic electrons produced in femtosecond laser-thin foil target interactions: characterization with nuclear techniques.

We present a protocol to characterize the high energy electron beam emitted in the interaction of an ultraintense laser with matter at intensities higher than 10(19) W cm(-2). The electron energies and angular distributions are determined as well as the total number of electrons produced above a 10 MeV threshold. This protocol is based on measurements with an electron spectrometer and nuclear activation techniques, combined with Monte Carlo simulations based on the GEANT3 code. The method is detailed and exemplified with data obtained with polypropylene and copper thin solid targets at a laser intensity of 2x10(19) W cm(-2). Special care is taken of the different sources of uncertainties. In particular, the reproducibility of the laser shots is considered.

Direct evidence of strongly inhomogeneous energy deposition in target heating with laser-produced ion beams.

We report on strong nonuniformities in target heating with intense, laser-produced proton beams. The observed inhomogeneity in energy deposition can strongly perturb equation of state (EOS) measurements with laser-accelerated ions which are planned in several laboratories. Interferometric measurements of the target expansion show different expansion velocities on the front and rear surfaces, indicating a strong difference in local temperature. The nonuniformity indicates at an additional heating mechanism, which seems to originate from electrons in the keV range.

Electron acceleration by a wake field forced by an intense ultrashort laser pulse.

Plasmas are an attractive medium for the next generation of particle accelerators because they can support electric fields greater than several hundred gigavolts per meter. These accelerating fields are generated by relativistic plasma waves-space-charge oscillations-that can be excited when a high-intensity laser propagates through a plasma. Large currents of background electrons can then be trapped and subsequently accelerated by these relativistic waves. In the forced laser wake field regime, where the laser pulse length is of the order of the plasma wavelength, we show that a gain in maximum electron energy of up to 200 megaelectronvolts can be achieved, along with an improvement in the quality of the ultrashort electron beam.

Relativistic electron generation in interactions of a 30 TW laser pulse with a thin foil target.

Energy and angular distributions of the fast outgoing electron beam induced by the interaction of a 1 J, 30 fs, 2 x 10(19) W/cm(2), 10 Hz laser with a thin foil target are characterized by electron energy spectroscopy and photonuclear reactions. We have investigated the effect of the target thickness and the intensity contrast ratio level on the electron production. Using a 6-microm polyethylene target, up to 4 x 10(8) electrons with energies between 5 and 60 MeV were produced per laser pulse and converted to gamma rays by bremsstrahlung in a Ta secondary target. The rates of photofission of U as well as photonuclear reactions in Cu, Au, and C samples have been measured. In optimal focusing conditions, about 0.06% of the laser energy has been converted to outgoing electrons with energies above 5 MeV. Such electrons leave the target in the laser direction with an opening angle of 2.5 degrees.

Low-energy measurement of the 7Be(p,gamma)8B cross section.

We have measured the cross section of the 7Be(p,gamma)8B reaction for E(c.m.) = 185.8, 134.7, and 111.7 keV using a radioactive 7Be target (132 mCi). Single and coincidence spectra of beta+ and alpha particles from 8B and 8Be* decay, respectively, were measured using a large acceptance spectrometer. The zero energy S factor inferred from these data is 18.5+/-2.4 eV b and a weighted mean value of 18.8+/-1.7 eV b (theoretical uncertainty included) is deduced when combining this value with our previous results at higher energies.

[Effectiveness of Haemophilus influenzae B-diphtheria conjugate vaccination in German children]. / Untersuchung zur Effektivität der Haemophilus-influenzae-B-Diphtherie-Konjugatimpfung bei deutschen Kindern.

BACKGROUND: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany. In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections. METHODS: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5. 1990-30.4. 1992. Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area. The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease. RESULTS: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded. Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively. None of these patients had been vaccinated except for one, who received two injections of Hib-D. Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study. Again, of these children only one child was vaccinated. As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml. The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection. In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib. CONCLUSIONS: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine. Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously. In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.

Solid-phase extraction of drugs from biological tissues--a review.

Solid-phase extraction procedures are being used increasingly in all types of drug testing laboratories, including those which carry out forensic toxicology. The advantages of such procedures include decreased operator time, reduced solvent volumes, and increased extraction efficiency. The application of existing techniques, however, has not yet been applied to tissues that are widely available postmortem. Tissue analysis can make the task of interpretation of drug levels much easier, particularly where unstable drugs are involved (e.g., cocaine). This review article explores the possibilities of applying existing extraction procedures to human tissue samples. We also consider the reasons why forensic laboratories have been slow to investigate such possibilities. We hope to stimulate interest in alternative tissue extraction procedures by reviewing reported procedures that apply to both human and animal tissue.

A rapid method for the determination of cocaine in brain tissue.

A rapid procedure is described for the extraction and analysis of brain samples for cocaine and benzoylecgonine. Human brain tissue was sectioned at autopsy, and samples were subjected to a lipase digestion, subsequent to solid-phase extraction. The distribution of cocaine and benzoylecgonine throughout different regions of the brain was determined by high-performance liquid chromatography.

The concept of the neuroleptic threshold: an update.

The authors review the development and the controversies of the neuroleptic threshold theory. According to this theory, the minimum effective antipsychotic dose of a neuroleptic ("threshold dose") correlates with the appearance of "fine motor" symptoms (micrography) as opposed to the appearance of manifest or "coarse motor" extrapyramidal side effects. About half of the acutely exacerbated schizophrenic patients respond to threshold doses, but no predictors are known to characterize the responders. The neuroleptic threshold doses were found to be low, and the low dose treatment strategy is supported by the results of current PET and neuroleptic plasma level studies.

[Correlation between immuno-morphological parameters of regional lymph nodes and the mortality of patients with stage I and II bronchial squamos cell carcinoma]. / Korrelationen zwischen immunmorphologischen Parametern regionärer Lymphknoten und der Uberlebenszeit operierter Patienten mit bronchialen Plattenepithelkarzinomen der Stadien I und II.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T 0/2, N 0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitive methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical "thymus dependent") area; volume of the follicular (predominantly B-cell) cortex and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded marcrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinushistiocytosis) correlated inversely with survival. Besides the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.

Immunomorphological lymph node changes in patients with operable bronchogenic squamous cell carcinoma.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T1/2, N0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients, 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitative methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical ("thymus-dependent") area; volume of the follicular (predominantly B-cell) cortex; and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded macrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinuhistiocytosis) correlated inversely with survival. In addition to the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.