Compression of sub-relativistic space-charge-dominated electron bunches for single-shot femtosecond electron diffraction

We demonstrate compression of 95 keV, space-charge-dominated electron bunches to sub-100 fs durations. These bunches have sufficient charge (200 fC) and are of sufficient quality to capture a diffraction pattern with a single shot, which we demonstrate by a diffraction experiment on a polycrystalline gold foil. Compression is realized by means of velocity bunching as a result of a velocity chirp, induced by the oscillatory longitudinal electric field of a 3 GHz radio-frequency cavity. The arrival time jitter is measured to be 80 fs

Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies

Background:This study aimed to define the maximally tolerated dose (MTD) of sunitinib combined with two different infusion schedules of ifosfamide. Methods:Patients with advanced solid tumours, good performance score, good organ function, and no standard therapy available were eligible. Continuous once daily sunitinib, in escalating doses per cohort, was combined with ifosfamide, 9 g m-2 for 3 days or 6 g m-2 for 5 days, administered every 3 weeks. Pharmacokinetic (PK) and pharmacodynamic (PD) assessments were performed. Results:With growth-factor support, the MTD of sunitinib combined with either ifosfamide schedule was 12.5 mg in 32 patients enrolled. Neutropenia-related adverse events were dose-limiting toxicities. Sunitinib did not affect ifosfamide PK. Ifosfamide significantly decreased exposure to sunitinib and increased exposure to its metabolite, SU12662. No consistent changes in PD parameters were observed. Conclusion:With growth-factor support, the MTD of sunitinib with both ifosfamide schedules was 12.5 mg. Ifosfamide produced decreased sunitinib blood levels because of CYP3A induction. As PK interactions cannot explain the relatively low sunitinib doses that can be combined with ifosfamide, synergy in toxicity is likely. Whether this also holds true for anti-tumour activity needs to be further explored.British Journal of Cancer advance online publication, 18 May 2010; doi:10.1038/sj.bjc.6605696 www.bjcancer.com

An ultrashort pulse ultra-violet radiation undulator source driven by a laser plasma wakefield accelerator

Narrow band undulator radiation tuneable over the wavelength range of 150–260 nm has been produced by short electron bunches from a 2 mm long laser plasma wakefield accelerator based on a 20 TW femtosecond laser system. The number of photons measured is up to 9 × 106 per shot for a 100 period undulator, with a mean peak brilliance of 1 × 1018 photons/s/mrad2/mm2/0.1% bandwidth. Simulations estimate that the driving electron bunch r.m.s. duration is as short as 3 fs when the electron beam has energy of 120–130 MeV with the radiation pulse duration in the range of 50–100 fs

Переходная зона между шельфом и континентальным склоном северной части Чёрного моря. Ландшафтный подход

На основе данных, полученных с применением обитаемых подводных аппаратов, рассмотрена проблема положения бровки шельфа как важной структурно фациальной границы морского бассейна. Описана ландшафтная фациальная зональность в диапазоне глубин 70–220 м в северной части Черного моря. Выявлено, что смена фаций в переходной зоне между шельфом и материковым склоном от бровки шельфа до глубины около 200 м находится в тесной связи с усилением гипоксии до полной аноксии.На основі даних, отриманих із застосуванням підводних апаратів, розглянуто проблему положення бровки шельфу як важливої структурно фаціальної межі морського басейну. Описано ландшафтну фаціальну зональність в діапазоні глибин 70–20 м у північній частині Чорного моря. Виявлено, що зміна фацій у перехідній зоні між шельфом і материковим схилом від бровки шельфу до глибини близько 200 м тісно пов’язана із збільшенням гіпоксії до повної аноксії.The problem of continental shelf break position as an important structural – facial marine basin boundary discussed on the basis of manned submersibles’ data. The range and setting of Northern Black Sea facial zones in the depths interval 70 220m are described. It’s found that the facial changes are related closely with hypoxia increasing to complete anoxia from the shelf break to the depth of about 200 m

Measurement of fraction unbound paclitaxel in human plasma

The clinical pharmacokinetic behavior of paclitaxel (Taxol) is distinctly nonlinear, with disproportional increases in systemic exposure with an increase in dose. We have recently shown that Cremophor EL, the formulation vehicle used for i.v. administration of paclitaxel, alters drug distribution as a result of micellar entrapment of paclitaxel, and we speculated that the free drug fraction (fu) is dependent on dose and time-varying concentrations of Cremophor EL in the central plasma compartment. To test this hypothesis, a reproducible equilibrium dialysis method has been developed for the measurement of paclitaxel fu in plasma. Equilibrium dialysis was performed at 37 degrees C in a humidified atmosphere of 5% CO(2) using 2.0-ml polypropylene test tubes. Experiments were carried out with 260-microliter aliquots of plasma containing a tracer amount of [G-(3)H]paclitaxel with high-specific activity against an equal volume of 0.01 M phosphate buffer (pH 7.4). Drug concentrations were measured by both reversed-phase HPLC and liquid scintillation counting. Using this method, fu has been measured in three patients receiving three consecutive 3-weekly courses of paclitaxel at dose levels of 135, 175, and 225 mg/m(2) and found to range between 0.036 and 0.079. The method was also used to define concentration-time profiles of unbound drug, estimated from the product of the total plasma concentration and fu

Dynamical Properties of small Polarons

On the basis of the two-site polaron problem, which we solve by exact diagonalization, we analyse the spectral properties of polaronic systems in view of discerning localized from itinerant polarons and bound polaron pairs from an ensemble of single polarons. The corresponding experimental techniques for that concern photoemission and inverse photoemission spectroscopy. The evolution of the density of states as a function of concentration of charge carriers and strength of the electron-phonon interaction clearly shows the opening up of a gap between single polaronic and bi-polaronic states, in analogy to the Hubbard problem for strongly correlated electron systems. The crossover regime between adiabatic and anti-adiabatic small polarons is triggered by two characteristic time scales: the renormalized electron hopping rate and the renormalized vibrational frequency becoming equal. This crossover regime is then characterized by temporarily alternating self- localization and delocalization of the charge carriers which is accompanied by phase slips in the charge and molecular deformation oscillations and ultimately leads to a dephasing between these two dynamical components of the polaron problem. We visualize these features by a study of the temporal evolution of the charge redistribution and the change in molecular deformations. The spectral and dynamical properties of polarons discussed here are beyond the applicability of the standard Lang Firsov approach to the polaron problem.Comment: 31 pages and 23 figs.(eps), accepted in the Phys. Rev.

Dose and schedule-finding study of oral topotecan and weekly cisplatin in patients with recurrent ovarian cancer

Both weekly cisplatin chemotherapy and single agent topotecan have proven to be effective in recurrent ovarian cancer. Preclinical data show synergism between cisplatin and topotecan. Side effects for this combination are drug sequence dependent and predominantly haematologic. Since preclinical data suggest that Cremophor EL (CrEL), the formulation vehicle of paclitaxel, has a protective effect on haematological toxicity of cisplatin, CrEL was added to the combination cisplatin and topotecan. In this phase I study, escalating doses of oral topotecan administered on day 1, 2, 8, 9, 15, 16, 29, 30, 36, 37, 43, 44 were combined with weekly cisplatin 70 mg m−2d−1on day 1, 8, 15, 29, 36, 43 (scheme A) or with the presumably less myelotoxic sequence weekly cisplatin day 2, 9, 16, 30, 37, 44 (scheme B). In scheme C, CrEL 12 ml was administered prior to cisplatin in the sequence of Scheme A. 18 patients have received a total of 85 courses. In scheme A 4/10 patients, all treated with topotecan 0.45 mg m−2d−1, experienced DLT: 1 patient had vomiting grade 4, 1 patient had grade 4 neutropenia >5 days, 1 patient had >2 weeks delay due to thrombocytopenia and 1 patient due to neutropenia. Both patients in scheme B (topotecan 0.45 mg m−2d−1) had DLT due to a delay > 2 weeks because of prolonged haematological toxicity. No DLT was observed in the first 3 patients in scheme C (topotecan 0.45 mg m−2d−1). However, 2 out of 3 patients treated at dose level topotecan 0.60 mg m−2d−1in scheme C experienced DLT due to >2 weeks delay because of persistent thrombocytopenia or neutropenia. We conclude that there is a modest clinical effect of CrEL on haematological toxicity for this cisplatin-based combination regimen, which seems to reduce these side effects but does not really enable an increase of the oral topotecan dose. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Simulated performance of an ultracold ion source

At present, the smallest spot size which can be achieved with state-of-the-art focused ion beam (FIB) technology is mainly limited by the chromatic aberrations associated with the 4.5 eV energy spread of the liquid-metal ion source. Here we numerically investigate the performance of an ultracold ion source which has the potential for generating ion beams which combine high brightness with small energy spread. The source is based on creating very cold ion beams by near-threshold photoionization of a laser-cooled and trapped atomic gas. We present ab initio numerical calculations of the generation of ultracold beams in a realistic acceleration field and including all Coulomb interactions, i.e., both space charge effects and statistical Coulomb effects. These simulations demonstrate that with existing technology reduced brightness values exceeding 105 A m-2 sr-1 V-1 are feasible at an energy spread as low as 0.1 eV. The estimated spot size of the ultracold ion source in a FIB instrument ranges from 10 nm at a current of 100 pA to 0.8 nm at 1 pA