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In this paper, two linear prediction algorithms and the Allan deviation are used to determine the uncertainty on time calibrations performed against predicted timescales. The proposed algorithms are shown to be close to optimal and have the advantage of bounding the timescale prediction error without requiring a noise model of the timescale process.

In this article, the interest of space environment for cold atoms is outlined. After a brief review of cooling techniques and Bose–Einstein condensation, the case of atomic clocks in microgravity is discussed. The scientific objectives of the European mission ACES are presented. ACES will fly onboard the international space station in 2005–2006.

Recently, microwave phase gradients were identified as the main source of uncertainty in the continuous fountain clock. Indeed, because of its particular geometry with two interaction zones, a dedicated research effort was necessary to reduce this effect. With the help of 3D finite element simulations and ultra-precise machining, we report here on the design and realization of a new kind of low phase gradient microwave cavity. The proposed geometry based on a ring waveguide of rectangular cross-section has a theoretical spatial phase variation of 30 μrad over the interaction zones, which corresponds to a predicted relative frequency shift below 10-15.

We report the results of a differential calibration of the time links between the Swiss Federal Office of Metrology (METAS) and the German Physikalisch Technische Bundesanstalt (PTB) in 2009 using a travelling state of the art GPS time and frequency transfer receiver. Neglecting possible long term variations of the GPS equipment, the estimated uncertainties of the calibration values are below 2 ns for all links. The results are verified by comparing them to the calibrated two way satellite time and frequency transfer (TWSTFT) link. Thereby it appears that, vice versa, a GPS calibration via a travelling receiver can indeed be used to calibrate a TWSTFT link with an uncertainty below 2 ns.

Geodetic GPS techniques based on dual-frequency phase and code measurements are now commonly used to perform time and frequency transfer. We present results from a dedicated experiment carried out to compare different types of geodetic GPS receivers and different processing techniques. Two time laboratories provide data from three different types of receivers as well as from Two-way time transfer and this dedicated data set is completed by data obtained from other laboratories participating to TAI. Comparisons of results between GPS analyses with two software packages and two processing techniques, and between GPS and TW are presented and discussed.

In the course of the year 2007, UTC(CH) will change from a computed time scale definition to one based on a realtime master clock. In preparation for this important change, the time scale generation hardware was upgraded and new control software is being developed. This paper discusses recent progress in the development of control and calibration methods used in the new time scale generation system and reports experimental results obtained during validation testing.

A fully automated two-way satellite time and frequency transfer (TWSTFT) station has" been built at METAS. This station has participated in the TWSTFT schedule on a regular basis since January 2005. In the Summer of 2006, the TWSTFT links between METAS, PTB and TUG were calibrated in a specific campaign using the mobile earth station of TUG. In the first part of this communication, technical details on the TWSTFT station at METAS and the data handling are presented. During the setting up of the earth station at METAS, special care was taken to ensure stable environmental conditions for the hardware. Emphasis was also placed on communication interfaces, made independent from the METAS LAN to avoid disruption of the automated TWSTFT station in the event of IT network failures. In the second part of the article, the calibration campaign and its outcome are described. The main result was the determination of the calibration constants of the links involved with combined uncertainties of 0.8 ns (1sigma). The calibration data have been reported in the result files since December 2006. With a fully automated and calibrated TWSTFT station at METAS, UTC(CH) can now be tied to UTC via TWSTFT measurements.

We address two issues that limit the quality of time and frequency transfer by carrier phase measurements from the Global Positioning System (GPS). The first issue is related to inconsistencies between code and phase observations. We describe and classify several types of events that can cause inconsistencies and observe that some of them are related to the internal clock of the GPS receiver. Strategies to detect and overcome time-code inconsistencies have been developed and implemented into the Bernese GPS software package. For the moment, only inconsistencies larger than the 20 ns code measurement noise level can be detected automatically. The second issue is related to discontinuities at the day boundaries that stem from the processing of the data in daily batches. Two new methods are discussed: clock handover and ambiguity stacking. The two approaches are tested on data obtained from a network of stations, and the results are compared with an independent time-transfer method. Both methods improve the stability of the transfer for short averaging times, but there is no benefit for averaging times longer than 8 days. We show that continuous solutions are sufficiently robust against modeling and preprocessing errors to prevent the solution from accumulating a permanent bias.

The Astronomical Institute of the University of Bern (AIUB) and the Swiss Federal Office of Metrology and Accreditation (METAS) have been collaborating to investigate and apply the use of the GPS carrier phase measurements (GPS CP) for time and frequency transfer. At METAS a dedicated hardware has been developed: the so-called geodetic time transfer terminal (GeTT-terminal) which was already presented to the community [Dudle, 1998]. In parallel the AIUB has implemented the capability for time and frequency transfer into the Bernese GPS software package [Hugentobler, 2001]. Within the last years several improvements of the analysis software for the time and frequency transfer have been implemented. The developments have been focused on overcoming the day boundary discontinuities. These occur in the resulting time series if the data are analyzed independently for each day. The magnitude of these artificial "clock jumps" depends on the mean noise behavior of the code observations and may typically reach a magnitude of up to one nanosecond. An important result of the software developments is the possibility to reconnect the phase ambiguity parameters at the day boundaries which allows to generate a continuous geodetic time and frequency transfer solution for a time interval that is only limited by a loss of lock to all satellites. This allows, in addition, to generate a geodetic frequency transfer solution without using the code measurements at all. Consequences for the geodetic time transfer learned from applying the geodetic phase-only frequency transfer method in several international campaigns are discussed in this paper

METAS is the Swiss Federal Office of Metrology and Accreditation, the METAS time & frequency laboratory (T&F Lab) operates a cesium primary standard, maintains the Swiss national time scales, disseminates precise time and performs calibrations for customers. This paper reports current activities in the laboratory

UTC(CH.R) is a hardware real-time realization of UTC(CH) generated from the reference cesium clock by means of a micro-phase-stepper. The purpose of the steering algorithm is to keep UTC(CH.R) as close as possible to UTC(CH) by means of a time-frequency control loop which must be stable despite the delay of 1 d between the epoch of the last computed state and the epoch of the daily steering. The paper presents the practical performance of the UTC(CH.R) realization based on measurement data recorded from April 2002 to April 2003. The performance of the UTC(CH.R) steering algorithm is compared against simulation results that apply alternative steering algorithms to the same free running clock data. In conclusion plans to use a hydrogen maser instead of a cesium clock for the generation of a future, improved UTC(CH.R) are discussed.

This paper presents a study of the transfer of frequency stability from an atomic reference to a quartz-crystal oscillator. The study is done for the cases of active and passive atomic frequency standards in which one makes use of a phase-lock loop and of a frequency-lock loop, respectively. The analysis is made in both the frequency and time domains and covers the cases of the hydrogen and rubidium masers and the passive cesium-and rubidium-frequency standards. The results obtained from numerical calculations are presented under the form of graphs. These results include the fractional frequency spectral density Sy(f) as a function of the Fourier frequency f, and the two sample variance ?2(?) as a function of ?, the sampling time.

A computer-controlled system for the measurement of the field distribution in microwave cavities is described. Examples of field measurements at various resonant frequencies are given for a cavity with a complex geometry.

The use of chlorambucil (CBL) for the chemotherapeutic treatment of cancer is often limited because of undesirable side effects due to its lack of specificity for cancer cells. Systemic effects such as renal toxicity, marrow aplasia, pulmonary fibrosis and gastrointestinal disorders may be eliminated or greatly reduced by increasing the specificity of the drug towards tumour cells. Carcinoembryonic antigen (CEA), an oncofoetal protein produced by some human cancer cells (Gold & Friedman, 1965), is extensively used as a clinical cancer marker for the follow-up of treated patients. We have already reported that this protein could be a target for daunorubicin-anti-CEA conjugates (Belles-Isles & Page, 1981; Page et al., 1981). Many authors have already described a method to adsorb chlorambucil to antitumour antibodies (Blakeslee & Kennedy,1974; Guclu et al., 1976), but in the previous applications of chlorambucilantibody conjugates, a certain percentage of the reported activity could have been due to the presence of a non-covalently bound aggregate of the drug (Blakeslee et al., 1975). The other method described for the covalent coupling of CBL (Tai et al., 1979) could lead to polymerisation of the carrier and needed a 2 h incubation in an aqueous solution. We present here a new method for the covalent binding of chlorambucil which allows a rapid coupling to proteins without any significant polymerisation. This was obtained using the isocyanate derivative of chlorambucil: 3-{4-[bis(2chloroethyl)amino]phenyl}propyl-1-isocyanate. The conjugate was separated from the remaining free drug by gel filtration on Sephadex G-25 (Pharmacia Fine Chemicals) and the drug:protein ratio was determined by a photofluorometric method to assay the alkylating activity of CBL (Bernier et al., 1983). This ratio could be varied by mixing various proportions of the drug derivative and of the antibody; in the assay conditions reported a ratio of 25 moles of drug per mole of antibody was used. The cytotoxic effects of chlorambucil-anti-CEA conjugates on LoVo cells (CEA producing human colon carcinoma cells) were evaluated by the inhibition of colony formation as already described (Emond & Page, 1982). Figure 1 illustrates that for any concentration of drug used, the highest inhibition of colony formation was obtained with the covalent drug-antibody conjugate. Also the antibodies were neither cytolytic nor cytostatic for these cells in vitro. The concentration required to obtain a 50% inhibition of colony formation (ID 50) was much lower for the conjugate than for the free drug, the physical mixture of both agents or chlorambucil conjugated to non-specific antibodies (anti-alphafoetoprotein). Experiments on non-CEA producing cells (CCL6; human amnions) showed the specificity of the CBL-anti-CEA conjugate for CEA producing cell lines (Table I). The contact period study (Figure 2) shows that a rapid binding of the CBL-anti-CEA conjugate allows a much higher pharmacological activity when compared to equimolar concentrations of the free drug.

The present work is devoted to the characterization and measurement of the phase instabilities produced by microwave amplifiers. We describe a special receiver designed for phase noise measurements at low Fourier frequencies. i.e. very close to the carrier in the spectral domain. Phase noise measurements of a microwave amplifier are presented and the noise floor of the receiver is shown and discussed.

This paper presents a study of the transfer of frequency stability from an atomic reference to a quartz-crystal oscillator. The study is done for the cases of active and passive atomic frequency standards in which one makes use of a phase-lock loop and of a frequency-lock loop, respectively. The analysis is made in both the frequency and time domains and covers the cases of the hydrogen and rubidium masers and the passive cesium-and rubidium-frequency standards. The results obtained from numerical calculations are presented under the form of graphs. These results include the fractional frequency spectral density Sy(f) as a function of the Fourier frequency f, and the two sample variance ?2(?) as a function of ?, the sampling time.

We report here a new method for the covalent coupling of chlorambucil to monoclonal anti-CEA using an isocyanate derivative of this drug. This method caused no polymerisation of the carrier and no aggregation of the drug. The inhibition of colony formation and of thymidine incorporation on LoVo cells showed an activity of the conjugate three to ten times higher than the one of the free drug or the physical mixture of both agents.

Even if the microwave frequency standards are widely used in our modern life, their reliability has not reached the level which is expected for a “mature” technical product, the type of the market requiring such a standards preventing, up to now, the “purification stage” which is typical of “consumer products”.

The paper describes work done on the Passive Rubidium Frequency Standard in order to identify and possibly improve its frequency stability in the short and long term region. In relation to the short term region, experiments are described which permit the identification of the major sources of noise and measurements are reported. A theoretical model is developed and conclusions are drawn relative to the optimization of the various parameters. In relation to the long term region, earlier work has shown that the power shift created by inhomogeneous broadening in the presence of a buffer gas and light shift could be a cause of instabilities. To avoid that effect we have started experiments on a wall coated cell without buffer gas and we report results on the wall shift and its temperature dependence. Although that type of cell avoids the power shift, it is observed that the temperature dependence of the wall shift is relatively large. These results are discussed in terms of earlier data obtained on rubidium masers.

A fluorescence assay is described which measures the alkylating activity of chlorambucil or its isocyanate derivative after photoactivation in the presence of dimethyl sulfoxide. This assay has a lower limit of sensitivity of 100 ng/mL and RSD of less than 10% for chlorambucil. The method requires less than 5 micrograms of alkylating agent and the fluorophore produced is stable for at least 24 h.

A compact and light-weight cavity with empty core and uniform field distribution is described contrary to dielectric loaded cavities. Only metallic losses are present. Thus the quality factor is reasonably high. An efficient and rigorous method yielding the resonant frequencies is described and theoretical results are compared with experimental measurements.

Results are presented on theoretical calculations of the signal-to-noise ratio and of the short-term stability realizable in passive rubidium frequency standards. Measurements made on systems using either the separate hyperfine filter or the integrated hyperfine filter approach are reported. It is concluded that shot noise produced by the lamp at the photodetector is responsible for the observed white frequency noise spectrum limiting the stability in the short-term region.

During May 2012, the CERN-CNGS neutrino beam has been operated for two weeks for a total of 1.8 10^17 pot in bunched mode, with a 3 ns narrow width proton beam bunches, separated by 100 ns. This tightly bunched beam structure allows a very accurate time of flight measurement of neutrinos from CERN to LNGS on an event-by-event basis. Both the ICARUS-T600 PMT-DAQ and the CERN-LNGS timing synchronization have been substantially improved for this campaign, taking ad-vantage of additional independent GPS receivers, both at CERN and LNGS as well as of the deployment of the "White Rabbit" protocol both at CERN and LNGS. The ICARUS-T600 detector has collected 25 beam-associated events; the corresponding time of flight has been accurately evaluated, using all different time synchronization paths. The measured neutrino time of flight is compatible with the arrival of all events with speed equivalent to the one of light: the difference between the expected value based on the speed of light and the measured value is tof_c - tof_nu = (0.10 \pm 0.67stat. \pm 2.39syst.) ns. This result is in agreement with the value previously reported by the ICARUS collaboration, tof_c - tof_nu = (0.3 \pm 4.9stat. \pm 9.0syst.) ns, but with improved statistical and systematic errors., Comment: 21 pages, 13 figures, 1 table