Coherent X-ray-optical control of nuclear excitons.

Coherent control of quantum dynamics is key to a multitude of fundamental studies and applications1. In the visible or longer-wavelength domains, near-resonant light fields have become the primary tool with which to control electron dynamics2. Recently, coherent control in the extreme-ultraviolet range was demonstrated3, with a few-attosecond temporal resolution of the phase control. At hard-X-ray energies (above 5-10 kiloelectronvolts), Mössbauer nuclei feature narrow nuclear resonances due to their recoilless absorption and emission of light, and spectroscopy of these resonances is widely used to study the magnetic, structural and dynamical properties of matter4,5. It has been shown that the power and scope of Mössbauer spectroscopy can be greatly improved using various control techniques6-16. However, coherent control of atomic nuclei using suitably shaped near-resonant X-ray fields remains an open challenge. Here we demonstrate such control, and use the tunable phase between two X-ray pulses to switch the nuclear exciton dynamics between coherent enhanced excitation and coherent enhanced emission. We present a method of shaping single pulses delivered by state-of-the-art X-ray facilities into tunable double pulses, and demonstrate a temporal stability of the phase control on the few-zeptosecond timescale. Our results unlock coherent optical control for nuclei, and pave the way for nuclear Ramsey spectroscopy17 and spin-echo-like techniques, which should not only advance nuclear quantum optics18, but also help to realize X-ray clocks and frequency standards19. In the long term, we envision time-resolved studies of nuclear out-of-equilibrium dynamics, which is a long-standing challenge in Mössbauer science20.

Tunable Subluminal Propagation of Narrow-band X-Ray Pulses.

Group velocity control is demonstrated for x-ray photons of 14.4 keV energy via a direct measurement of the temporal delay imposed on spectrally narrow x-ray pulses. Subluminal light propagation is achieved by inducing a steep positive linear dispersion in the optical response of 57Fe Mössbauer nuclei embedded in a thin film planar x-ray cavity. The direct detection of the temporal pulse delay is enabled by generating frequency-tunable spectrally narrow x-ray pulses from broadband pulsed synchrotron radiation. Our theoretical model is in good agreement with the experimental data.

Tet3 mediates stable glucocorticoid-induced alterations in DNA methylation and Dnmt3a/Dkk1 expression in neural progenitors.

Developmental exposure to excess glucocorticoids (GCs) has harmful neurodevelopmental effects, which include persistent alterations in the differentiation potential of embryonic neural stem cells (NSCs). The mechanisms, however, are largely unknown. Here, we investigated the effects of dexamethasone (Dex, a synthetic GC analog) by MeDIP-like genome-wide analysis of differentially methylated DNA regions (DMRs) in NSCs isolated from embryonic rat cortices. We found that Dex-induced genome-wide DNA hypomethylation in the NSCs in vitro. Similarly, in utero exposure to Dex resulted in global DNA hypomethylation in the cerebral cortex of 3-day-old mouse pups. Dex-exposed NSCs displayed stable changes in the expression of the DNA methyltransferase Dnmt3a, and Dkk1, an essential factor for neuronal differentiation. These alterations were dependent on Tet3 upregulation. In conclusion, we propose that GCs elicit strong and persistent effects on DNA methylation in NSCs with Tet3 playing an essential role in the regulation of Dnmt3a and Dkk1. Noteworthy is the occurrence of similar changes in Dnmt3a and Dkk1 gene expression after exposure to excess GC in vivo.

Ticks and tick-borne pathogens in South Bohemia (Czech Republic)--Spatial variability in Ixodes ricinus abundance, Borrelia burgdorferi and tick-borne encephalitis virus prevalence.

Spatial distribution of Ixodes ricinus tick host-seeking activity, as well as prevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) were studied in the TBE endemic area of South Bohemia (Czech Republic). High variability in tick abundance detected in a network of 30 study sites was most closely associated with characteristics of vegetation cover. Of 11,182 tested tick samples, 12% carried DNA of spirochete from B. burgdorferi s.l. complex. B. afzelii and B. garinii prevailed among spirochete species. The presence of B. spielmanii in the region was confirmed. The median number of borrelial genome copies in positive samples reached 6.6 × 10(3) by real-time PCR. The total prevalence of TBEV in pooled samples reached 0.32% (20,057 samples tested), at least one TBEV positive tick was present in 21 out of 30 sampling sites.

Vacuum-assisted generation and control of atomic coherences at x-ray energies.

The control of light-matter interaction at the quantum level usually requires coherent laser fields. But already an exchange of virtual photons with the electromagnetic vacuum field alone can lead to quantum coherences, which subsequently suppress spontaneous emission. We demonstrate such spontaneously generated coherences (SGC) in a large ensemble of nuclei operating in the x-ray regime, resonantly coupled to a common cavity environment. The observed SGC originates from two fundamentally different mechanisms related to cooperative emission and magnetically controlled anisotropy of the cavity vacuum. This approach opens new perspectives for quantum control, quantum state engineering and simulation of quantum many-body physics in an essentially decoherence-free setting.

The law concerning teenage sex: do we understand it?

Recent child protection reports and changes in sexual offences laws in England and Wales have altered the ethical and legal landscape for health professionals working with sexually active young people. This study aimed to identify the educational needs of a sample of those professionals. A true/false questionnaire was developed comprising statements concerning sexual activity in young people. We sent it to a sample of Family Planning staff, genitourinary (GU) medicine nurses and doctors in 102 Family Planning and 261 GU-medicine clinics throughout England and Wales. A total of 168 completed questionnaires were returned. The range of correct responses for the whole group was between 2 and 10 out of 10, with a median of 6. We identified some misunderstanding concerning the term 'Fraser' competence and the legal basis on which contraception can be provided to under 16-year olds, as well as some lack of awareness concerning present advice on child protection. In free text responses, many people volunteered educational needs.

New visualization tools: computer vision and ultrasound for MIS navigation.

BACKGROUND: A versatile image acquisition method called echo surgetics has been developed for minimally invasive computer-assisted orthopaedic procedures. The principle of echo surgetics is to use freehand three-dimensional (3D) ultrasound to acquire relevant 3D bone surface and point data transcutaneously, eliminating access problems associated with conventional digitizers. The concept has been implemented in three technologies: Echo Point, Echo Matching and Echo Morphing. METHODS: Cadaver experiments were carried out to evaluate the accuracy of (a) Echo Point for digitization of the anterior pelvic plane (APP) in total hip arthroplasty, and (b) Echo Morphing for reconstructing the distal femur in minimally invasive knee surgery. RESULTS AND CONCLUSIONS: Echo Point provided significantly improved results (p < 0.001) over conventional digitization where mean tilt errors exceeded 20 degrees . The Echo Morphing experiments demonstrated that with a reasonable number of points (ca. 1000) and initial attitude (IA) error (ca. 5-10 mm and 5-10 degrees ) we can obtain an average accuracy of approximately 1 mm that is sufficient for most of clinical applications.

The use of ultrasound in acquisition of the anterior pelvic plane in computer-assisted total hip replacement: a cadaver study.

We have evaluated in vitro the accuracy of percutaneous and ultrasound registration as measured in terms of errors in rotation and version relative to the bony anterior pelvic plane in computer-assisted total hip replacement, and analysed the intra- and inter-observer reliability of manual or ultrasound registration. Four clinicians were asked to perform registration of the landmarks of the anterior pelvic plane on two cadavers. Registration was performed under four different conditions of acquisition. Errors in rotation were not significant. Version errors were significant with percutaneous methods (16.2 degrees; p < 0.001 and 19.25 degrees with surgical draping; p < 0.001), but not with the ultrasound acquisition (6.2 degrees, p = 0.13). Intra-observer repeatability was achieved for all the methods. Inter-observer analysis showed acceptable agreement in the sagittal but not in the frontal plane. Ultrasound acquisition of the anterior pelvic plane was more reliable in vitro than the cutaneous digitisation currently used.

EPs 7630, an extract from Pelargonium sidoides roots inhibits adherence of Helicobacter pylori to gastric epithelial cells.

Helicobacter pylori specifically adheres to gastric host cells, mainly based on carbohydrate-mediated cell-cell interaction. The extract of Pelargonium sidoides roots (EPs) 7630), a South African herbal remedy, is currently used to treat acute bronchitis. EPs 7630 prevents bacteria from attaching to cell membranes. Therefore, the ability of EPs 7630 to interfere with H. pylori growth and adhesion to gastric epithelial cells (AGS cells) was tested in vitro. EPs 7630 inhibited H. pylori growth and with higher potency adhesion to gastric AGS cells. EPs 7630 (50 and 100 microg/ml) reduced bacterial count attached to AGS cells by 77% and 91%, respectively. The results suggest that the mode of action of EPs 7630 is mainly related to its anti-adhesive activity.

Bis(imino)pyridine cobalt alkyl complexes and their reactivity towards ethylene: a model system for beta-hydrogen chain transfer.

Bis(imino)pyridine cobalt(I) n-alkyl complexes react with ethylene by beta-hydrogen transfer, allowing direct study of a termination step commonly encountered in polymerisation and oligomerisation catalysis.

Exposure to armament wastes and leukemia: a case-control study within a cluster of AML and CML in Germany.

An unusually high incidence of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) concentrated in a specific locality of a region in Germany motivated a descriptive incidence study in that region which showed a near 10-fold increased risk of CML among males but not among females (Kolb G, Becker N, Scheller S, Zugmaier G, Pralle H, Wahrendorf J, Havemann K. Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a County of Hesse, Germany, Soc Prev Med 1993;38:190-195). Since a serious environmental contamination of areas in this locality with armament wastes containing toluene-derivatives has been known for a long time, the hypothesis arose that TNT production and the related severe contamination of soil and water might be responsible for the observed higher risk. We carried out a case-control study within the cluster to test this hypothesis. Overall, the results do not confirm the hypothesis. There is an indication of a relationship of an increased odds ratio with the exposure for a small group of persons who lived at a particular site in one of the two communities involved during the peak phase of TNT production during the 1940s. However, this finding is spurious and cannot explain the large majority of cases which occurred in that area in the 1980s. At the moment, no other explanation can be given for the increased risk of leukemias in that area.

Novel small organo-P-S/Se heterocycles.

Oxidative addition of elemental sulfur and selenium to cyclomonocarbatetraphosphines (PhP)4CR2 (R = H, Me) afforded novel five- and four-membered heterocycles PhP(E)CH2PhP(E)E2(E = S, Se) and PhP(Se)CMe2-PhP(Se)Se.

Pepsinogen synthesis during long-term culture of porcine chief cells.

The purpose of this study was to characterize time-dependent changes in pepsinogen (PG) synthesis of porcine gastric chief cells during long-term monolayer culture. Porcine chief cells were isolated by pronase/collagenase treatment of fundic mucosa and enriched by density gradient and counterflow centrifugation. PG isoenzymes were identified in [L-35S]methionine-labelled cultured chief cells by native polyacrylamide gel electrophoresis followed by phosphor imager analysis, protease detection and immunoblots with specific PG A and C antibodies. The obtained results suggest that porcine chief cell cultures, after an initial settling period, reached an approximate steady state in total protein content and synthesis as well as in PG content and isoenzyme pattern from days 3 to 9 of culture. The latter was characterized by the presence of at least two PG A and two PG C isoenzymes. During the supposed steady-state total PG synthesis averaged out at 34 +/- 2% of total protein synthesis, as detected by [L-35S]methionine incorporation, due to the synthesis of, mainly, PG A2 and, to a much lesser extent, PG C and A1. In line with an active secretion, PG A2 proportion was on average significantly higher in released (44 +/- 3%) than in intracellular labelled proteins (19 +/- 2%). In addition, PG release from chief cells cultured for 6 and 9 days could be stimulated by cholecystokinin-octapeptide. These data suggest that porcine chief cells in monolayer culture are a model well suited for the quantitative and qualitative characterization of PG isoenzyme synthesis and release during long-term investigations, for which an establishment of a culture steady state appears to be a useful prerequisite.

Recovery of cholecystokinin response of porcine gastric chief cells during monolayer culture.

Cell isolation may impair secretory chief cell functions. To evaluate whether a monolayer culture results in a recovery, we compared the effects of cholecystokinin (CCK) octapeptide (CCK-8) on pepsinogen release from freshly isolated and from cultured porcine chief cells. CCK-8 had no significant effect on freshly isolated porcine chief cells but stimulated pepsinogen release from 36- and 60-hour cultured cells with EC50 values of 180 and 130 nmol/l, respectively. Maximal stimulation, achieved at a concentration of 1 micromol/l, amounted to 289 +/- 63 (p <0.01) and 401 +/- 64% (p <0.01) of the respective control value. In addition, the CCK-8 concentration-response curve for 60-hour, but not for 36-hour cultured chief cells displayed a second stimulatory peak at a CCK-8 concentration of 100 pmol/l (266 +/- 55% of control value, p < 0.05) with an EC50 value of 16 pmol/l. The CCKA-receptor antagonist devazepide (10 nmol/l) prevented the stimulatory effect of 1 micromol/l CCK-8 on pepsinogen release of 60-hour cultured cells. The adenylate cyclase activator forskolin (10 micromol/l) potentiated the low concentration CCK-8 effect, shifting the peak stimulation to a CCK-8 concentration of 10 pmol/l, and inhibited the high concentration CCK-8 effect on 60-hour cultured cells. These results indicate a time-dependent recovery of the CCK response of porcine gastric chief cells in monolayer culture and suggest that this model has an advantage over freshly isolated chief cells with regard to the pharmacological characterization of CCK effects.

Interleukin-1 (IL-1) receptors on murine splenic B cells and the 70Z/3 pre-B-cell line appear to be identical and bind human IL-1 alpha and IL-1 beta differentially.

In this study murine splenocytes were found to possess specific, high-affinity IL-1 receptors (IL-1R) capable of binding radiolabeled human IL-1 alpha with a Kd of 2-6 x 10(-10) M. Experiments performed with purified splenic B cells demonstrated that B cells express low levels of IL-1R (100-200 receptors per cell). Separation of splenic B cells into high- (resting) and low-density (in vivo-activated) fractions showed that low-density B cells expressed 2-fold more IL-1R compared with high-density B cells suggesting that IL-1R are upregulated on B-cell activation. In vitro stimulation of B cells with mitogens resulted in a 5- to 10-fold increase in IL-1R expression compared to IL-1R levels on unstimulated B cells. Receptors on the murine pre-B-cell line 70Z/3, which possesses type II IL-1R, and murine splenic B cells appear to be identical. Cross-linking studies demonstrated that the 125I-labeled IL-1/IL-1R complex on B cells and 70Z/3 IL-1R was found to block binding of IL-1 to IL-1R on 70Z/3 and splenic B cells, but not to type I IL-1R on murine EL4 thymoma cells. Competitive inhibition experiments showed differential binding of human IL-1 beta to splenic B cells and 70Z/3 cells as a function of temperature. The IL-1R on 70Z/3 and splenic B cells bound human IL-1 alpha, murine IL-1 alpha, and murine IL-1 beta with high affinity at both 4 degrees and 37 degrees C. In contrast, the affinity of IL-1R on these same cell types for human IL-1 beta was significantly reduced at 37 degrees C compared to 4 degrees C. The reduced binding affinity for human IL-1 beta was due to an increased off-rate at 37 degrees C compared with 4 degrees C. Characterization of IL-1R on murine splenic B cells will help clarify the role of IL-1 in the regulation of the immune response.

Type I IL-1 receptor blockade exacerbates murine listeriosis.

It was found that IL-1 is produced in livers and spleens of mice shortly after the i.v. injection of a sublethal or lethal Listeria monocytogenes inoculum. In sublethally infected mice, IL-1 was present in infected livers and spleens by the end of the first day of infection. Thereafter, the amounts of IL-1 in these organs increased and decreased in concordance with bacterial numbers. IL-1 was not present in the peripheral circulation of mice during sublethal listeriosis, but was present in the blood late in lethal infection. Evidence showing that IL-1 plays a role in antibacterial resistance early in listeriosis was obtained through the use of 35F5 mAb that binds to the murine type I IL-1R and functions to block IL-1 alpha and IL-1 beta actions. Blockade of the type I IL-1R by the 35F5 mAb results in greatly enhanced bacterial growth in the livers and spleens of mice that had received a sublethal Listeria inoculum. Consistent with the exacerbation of listeriosis caused by 35F5 mAb, but in contrast to the effect of 35F5 mAb in other murine models, 35F5 mAb-treated mice exhibit markedly elevated levels of IL-6 in their circulation and infected organs.

Failure of IL-1 receptor antagonist and monoclonal anti-IL-1 receptor antibody to inhibit antigen-specific immune responses in vivo.

rIL-1R antagonist (rIL-1ra) and 35F5, a neutralizing mAb, have been shown to inhibit the ability of IL-1 alpha and IL-1 beta to bind to type I but not type II murine receptors. Additionally, IL-1ra and 35F5 inhibit a variety of inflammatory responses in vitro and in vivo. In the present report we have evaluated the activity of human IL-1ra and 35F5 in murine Ag-specific cell-mediated and humoral immune response models. Administration of IL-1ra, either twice daily or as a continuous infusion, did not inhibit the cytolytic T lymphocyte response to allogeneic splenocytes. The CTL response was also not inhibited by daily administration of 35F5. The delayed type hypersensitivity response to oxazolone was similarly refractory to administration of IL-1ra and 35F5. In the humoral immune response models, neither the splenic plaque response to SRBC nor the IgG or IgM response to TNP-keyhole limpet hemocyanin was inhibited by treatment with IL-1ra or 35F5. These data suggest that signaling through the type I IL-1R is not required for these Ag-specific immune responses.

Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor.

Human interleukin 1 beta (IL-1 beta) exerts its diverse biological effects by binding to specific receptors on target cells. Two types of IL-1 receptor (IL-1R) have been identified: the type I IL-1R (p80) and the type II IL-1R (p68). Using site-specific mutagenesis, we have identified the binding site on IL-1 beta for the murine type I IL-1R. Analogs of the IL-1 beta protein containing defined amino acid substitutions were produced and tested for competitive binding to the two IL-1Rs. Substitutions of the amino acids at seven positions resulted in analogs that had greater than or equal to 100-fold reductions in competitive binding to the type I IL-1R, while maintaining substantial binding to the type II IL-1R. These seven amino acids (Arg-4, Leu-6, Phe-46, Ile-56, Lys-93, Lys-103, and Glu-105) are clustered in the IL-1 beta molecule, forming a discontinuous binding site. The side chains of all seven residues are exposed on the surface of IL-1 beta. The cumulative binding energies contributed by each of the residues predict a binding affinity that is consistent with the observed Kd of the wild-type protein for the type I IL-1R.