Improvement of an Atomic Clock using Squeezed Vacuum.

Since the pioneering work of Ramsey, atom interferometers are employed for precision metrology, in particular to measure time and to realize the second. In a classical interferometer, an ensemble of atoms is prepared in one of the two input states, whereas the second one is left empty. In this case, the vacuum noise restricts the precision of the interferometer to the standard quantum limit (SQL). Here, we propose and experimentally demonstrate a novel clock configuration that surpasses the SQL by squeezing the vacuum in the empty input state. We create a squeezed vacuum state containing an average of 0.75 atoms to improve the clock sensitivity of 10000 atoms by 2.05_{-0.37}^{+0.34} dB. The SQL poses a significant limitation for today's microwave fountain clocks, which serve as the main time reference. We evaluate the major technical limitations and challenges for devising a next generation of fountain clocks based on atomic squeezed vacuum.

Satisfying the Einstein-Podolsky-Rosen criterion with massive particles.

In 1935, Einstein, Podolsky and Rosen (EPR) questioned the completeness of quantum mechanics by devising a quantum state of two massive particles with maximally correlated space and momentum coordinates. The EPR criterion qualifies such continuous-variable entangled states, where a measurement of one subsystem seemingly allows for a prediction of the second subsystem beyond the Heisenberg uncertainty relation. Up to now, continuous-variable EPR correlations have only been created with photons, while the demonstration of such strongly correlated states with massive particles is still outstanding. Here we report on the creation of an EPR-correlated two-mode squeezed state in an ultracold atomic ensemble. The state shows an EPR entanglement parameter of 0.18(3), which is 2.4 s.d. below the threshold 1/4 of the EPR criterion. We also present a full tomographic reconstruction of the underlying many-particle quantum state. The state presents a resource for tests of quantum nonlocality and a wide variety of applications in the field of continuous-variable quantum information and metrology.

Interaction-free measurements by quantum Zeno stabilization of ultracold atoms.

Quantum mechanics predicts that our physical reality is influenced by events that can potentially happen but factually do not occur. Interaction-free measurements (IFMs) exploit this counterintuitive influence to detect the presence of an object without requiring any interaction with it. Here we propose and realize an IFM concept based on an unstable many-particle system. In our experiments, we employ an ultracold gas in an unstable spin configuration, which can undergo a rapid decay. The object-realized by a laser beam-prevents this decay because of the indirect quantum Zeno effect and thus, its presence can be detected without interacting with a single atom. Contrary to existing proposals, our IFM does not require single-particle sources and is only weakly affected by losses and decoherence. We demonstrate confidence levels of 90%, well beyond previous optical experiments.

Twin matter waves for interferometry beyond the classical limit.

Interferometers with atomic ensembles are an integral part of modern precision metrology. However, these interferometers are fundamentally restricted by the shot noise limit, which can only be overcome by creating quantum entanglement among the atoms. We used spin dynamics in Bose-Einstein condensates to create large ensembles of up to 10(4) pair-correlated atoms with an interferometric sensitivity -1.61(-1.1)(+0.98) decibels beyond the shot noise limit. Our proof-of-principle results point the way toward a new generation of atom interferometers.

Spontaneous breaking of spatial and spin symmetry in spinor condensates.

Parametric amplification of quantum fluctuations constitutes a fundamental mechanism for spontaneous symmetry breaking. In our experiments, a spinor condensate acts as a parametric amplifier of spin modes, resulting in a twofold spontaneous breaking of spatial and spin symmetry in the amplified clouds. Our experiments permit a precise analysis of the amplification in specific spatial Bessel-like modes, allowing for the detailed understanding of the double symmetry breaking. On resonances that create vortex-antivortex superpositions, we show that the cylindrical spatial symmetry is spontaneously broken, but phase squeezing prevents spin-symmetry breaking. If, however, nondegenerate spin modes contribute to the amplification, quantum interferences lead to spin-dependent density profiles and hence spontaneously formed patterns in the longitudinal magnetization.

Development of highly active and selective novel Pd based acetoxylation catalysts and prevention of catalyst deactivation by Bi modification.

A first approach to successful prevention of catalyst deactivation while simultaneously achieving extremely high selectivity of benzyl acetate (> or = 95%) at significantly high toluene conversion (> 70%) by gas phase acetoxylation over novel Pd-Sb-Bi/TiO2 catalysts.

One-step synthesis of benzyl acetate by gas phase acetoxylation of toluene over highly active and selective Pd-Sb-TiO2 catalysts.

Significantly high benzyl acetate selectivity of 85% at a toluene conversion of ca. 93% was achieved for the first time in a single step by gas phase acetoxylation over highly active and selective Pd-Sb-TiO2 catalysts.

Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1.

Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1. Its product is involved in various cellular processes, including cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA processing and activation of transcription. Spinal muscular atrophy with respiratory distress (SMARD) is clinically and genetically distinct from SMA. Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4). In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus. Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals.

Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the alpha-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers.

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)

High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer--a phase II study in elderly patients or patients with cardiac risk.

Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.

Dopamine stimulated glycosylation of brain proteins in vitro is inhibited only partially by dopamine receptor antagonists.

Dopaminergic agonists which act on adenylate cyclase-linked dopamine receptor sites (D1-type) (dopamine, apomorphine and ADTN) induced a dose-dependent increase in the incorporation of L-fucose and D-mannose into glycoproteins of hippocampal, striatal and cortical slices of rat and mouse brain, whilst in rat liver slices dopamine failed to elicit such alterations in protein glycosylation. Testing in slices of rat hippocampus dopaminergic agonists with selective affinity to D2-receptors (bromocriptine, ergometrine) no changes in sugar incorporation into glycoproteins of rat hippocampus were observed. Dopamine stimulated L-fucose incorporation into rat hippocampal glycoproteins was inhibited to a different degree, but almost incompletely by dopamine receptor antagonists like haloperidol, D-butaclamol, promazine and alpha-flupenthixol, whilst chloropromazine and the selective D2-receptor antagonist sulpiride were without any effects. Also serotonin receptor antagonists (cinanserine) and beta-adrenergic receptor blockers (pindolol, alprenolol, practolol) failed to interfere with this dopamine action. But D,L-propranolol enhanced dopamine stimulated glycosylation of rat hippocampal proteins in an additive synergistic manner. This effect appeared to be not related to the antagonistic action of propranolol on beta-adrenergic receptor sites. From our results it is concluded that interactions with dopamine receptor sites (D1-type) is only one part of the mechanism triggering dopamine stimulated glycosylation of brain proteins in vitro.

Erythromycin infusions for treatment of infections in the ear, nose and throat region.

Sixteen adult male patients (aged between 20-38 years) with ear, nose and throat infections, caused by bacteria sensitive to erythromycin, received daily infusions of 2 x 1 g erythromycin for 48 hours. The duration of infusion was 30 or 60 minutes, administered at intervals of 12 hours between infusions. Symptoms of intolerance such as nausea, retching, feeling of pressure in epigastric angle as well as abdominal cramps occurred as side-effects in many cases. A spasmolytic was given intravenously to twelve patients; it rapidly eliminated the symptoms. However, these side-effects were considered insignificant compared to the excellent clinical results obtained during infusion therapy. We, therefore, believe that 2 x 1 g/day erythromycin per infusion can be regarded as the drug of choice in chronic and acute ear, nose and throat infections. The rapid resolution of infections, which are otherwise difficult to treat, and the concomitant decrease in confinement to bed by about 8 to 10 days are the most important results in this study.