Author Correction: Nanofocusing of hard X-ray free electron laser pulses using diamond based Fresnel zone plates.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comparison of two x-ray phase-contrast imaging methods with a microfocus source.

We present a comparison for high-resolution imaging with a laboratory source between grating-based (GBI) and propagation-based (PBI) x-ray phase-contrast imaging. The comparison is done through simulations and experiments using a liquid-metal-jet x-ray microfocus source. Radiation doses required for detection in projection images are simulated as a function of the diameter of a cylindrical sample. Using monochromatic radiation, simulations show a lower dose requirement for PBI for small object features and a lower dose for GBI for larger object features. Using polychromatic radiation, such as that from a laboratory microfocus source, experiments and simulations show a lower dose requirement for PBI for a large range of feature sizes. Tested on a biological sample, GBI shows higher noise levels than PBI, but its advantage of quantitative refractive index reconstruction for multi-material samples becomes apparent.

X-ray submicrometer phase contrast imaging with a Fresnel zone plate and a two dimensional grating interferometer.

The application of a two dimensional (2D) grating interferometer-Fresnel zone plate combination for quantitative submicron phase contrast imaging is reported. The combination of the two optical elements allows quick recovery of the phase shift introduced by a sample in a hard X-ray beam, avoiding artifacts observed when using the one dimensional (1D) interferometer for a sample with features oriented in the unsensitive direction of the interferometer. The setup provides submicron resolution due to the optics magnification ratio and a fine sensitivity in both transverse orientations due to the 2D analysis gratings. The method opens up possibilities for sub-micro phase contrast tomography of microscopic objects made of light and/or homogeneous materials with randomly oriented features.

Sensitivity of X-ray grating interferometry.

It is known that the sensitivity of X-ray phase-contrast grating interferometry with regard to electron density variations present in the sample is related to the minimum detectable refraction angle. In this article a numerical framework is developed that allows for a realistic and quantitative determination of the sensitivity. The framework is validated by comparisons with experimental results and then used for the quantification of several influences on the sensitivity, such as spatial coherence or the number of phase step images. In particular, we identify the ideal inter-grating distance with respect to the highest sensitivity for parallel beam geometry. This knowledge will help to optimize existing synchrotron-based grating interferometry setups.

Nanofocusing of hard X-ray free electron laser pulses using diamond based Fresnel zone plates.

A growing number of X-ray sources based on the free-electron laser (XFEL) principle are presently under construction or have recently started operation. The intense, ultrashort pulses of these sources will enable new insights in many different fields of science. A key problem is to provide x-ray optical elements capable of collecting the largest possible fraction of the radiation and to focus into the smallest possible focus. As a key step towards this goal, we demonstrate here the first nanofocusing of hard XFEL pulses. We developed diamond based Fresnel zone plates capable of withstanding the full beam of the world's most powerful x-ray laser. Using an imprint technique, we measured the focal spot size, which was limited to 320 nm FWHM by the spectral band width of the source. A peak power density in the focal spot of 4×10(17)W/cm(2) was obtained at 70 fs pulse length.

A problem-based preclinical course for dental students.

In September 1994 the Turner Dental School, University of Manchester, introduced a new curriculum in which the first 2 years were problem-oriented. The 82 dental students share the first year and part of the second with 252 medical students, making this the largest cohort of students in a problem-based learning course in the world. It is one of two or three dental courses of its kind. In addition to the problem-oriented work, the course includes a substantial informatics component involving computer skills. The number of lectures has been reduced to a maximum of four per week in the first year and seven per week in the second. Most of the students' learning is achieved by group work in which they study clinical cases and search out the basic biological background to them. At the same time the students consider the social and psychological implications of the cases and develop their own communication skills. Thus far the course has resulted in students having a much broader but less detailed subject knowledge. Students are able to integrate their knowledge more effectively. In the new kinds of examination developed for the course the dental students achieve marks around 5% lower than their medical colleagues, as in more traditional combined courses. The first year of the course was designed for medical students and may not therefore be optimal for dental students but the second year has more specifically dental components.

Toward an animal model of chronic pancreatitis. Pancreatobiliary secretion in hamsters on long-term treatment with chemical inducers of cytochromes P450.

There is currently no reproducible model of the painful and lithogenic disease, chronic pancreatitis. Its biphasic evolution, from acinar cell hyperplasia and hyperactivity toward effacement of enzyme as well as bicarbonate secretory parenchyma, would be rationalized if it was linked to induction of cytochrome P450 mono-oxygenases (CYP): the increased oxidant load from long-term CYP induction eventually erodes micronutrient antioxidant defenses to injure cells. This philosophy would also rationalize the reported hepatobiliary aberrations associated with the human disease, including increases in free radical oxidation products in bile. Accordingly, pancreatic and biliary secretions were studied in Syrian golden hamsters that were reared for 6 mo on low or high (16% corn oil) fat diets that were supplemented with a prototype inducer of CYP2 (200 ppm phenobarbitone) or CYP1 (100 ppm beta naphthoflavone) enzyme families, with or without a putative enzyme inhibitor (400 ppm cimetidine). The drugs did not alter the reduction in flow rate or bicarbonate concentration of pancreatic juice caused by the high fat diet alone, but, in contrast, evoked pancreatic protein hypersecretion in a number of animals. beta naphthoflavone, but not phenobarbitone, augmented the output of biliary lipid peroxidation products irrespective of dietary fat content, and cimetidine cotreatment with either inducer did the same. We conclude: (1) that drug modifiers of CYP magnify the deleterious pancreatobiliary effects of corn oil-enriched diets and draw them closer to those found in human chronic pancreatitis; (2) that these functional derangements are accompanied by pancreatic lipoatrophy; and (3) that long-term CYP induction does not, of its own, cause fibrosis or the ductal abnormalities that generally accompany loss of pancreatic acinar cells in the human disease and, also in contrast, the changes that are caused appear to be painless.

The effects of hypertonic glucose solutions on hepatic bile formation.

Bile secretion in the isolated guinea-pig liver was studied during perfusion with equi-osmolar hypertonic solutions containing either glucose, galactose, mannose, mannitol or sodium chloride. Perfusates made hypertonic with glucose, galactose or mannose decreased bile flow to the same extent and had similar effects on the ionic composition of bile: sodium, potassium and bicarbonate concentrations all increased. Mannitol had a smaller inhibitory effect and caused different changes in ionic composition: the increase in bile potassium concentration was proportionately greater; bicarbonate concentration did not change, but chloride was increased. Thus, glucose, galactose and mannose, can inhibit bile flow independently of extrinsic neural and hormonal mechanisms and exert a greater cholestatic effect than a non-metabolisable carbohydrate of similar molecular weight. The results also provide evidence for glucose reabsorption in the guinea-pig biliary tree, as shown in other species, and that galactose competes for this transport.

Pancreatic and biliary secretion in the anesthetized Syrian golden hamster in response to secretin, cholecystokinin-octapeptide, bombesin, and carbachol.

The aim of this study was to characterize pancreatic and biliary secretion in the anesthetized Syrian golden hamster. There were spontaneous secretions of both pancreatic juice and bile, which were increased by 400% and 60% by optimal doses of secretin with parallel increases in bicarbonate concentrations to 150 and 80 mM, respectively. CCK-8 and bombesin had little or no effect on pancreatic water and electrolyte secretion, whereas carbachol increased flow rate and bicarbonate concentration. CCK-8, bombesin, and carbachol all increased pancreatic protein secretion but had no effect on biliary secretion. In conclusion, the patterns of pancreatic and biliary secretion in the hamster are different from those in other rodents but are quite similar to those in humans.

The feasibility of students with a predominantly arts educational background coping with the physiology component of a university nursing degree programme.

In this paper the authors discuss their experiences in admitting students with an arts 'A' (advanced) level General Certificate of Education background to an undergraduate nursing degree course. Firstly, the implications of students' different cognitive styles, both professionally and in teaching, are examined. Secondly, there is a description of an introductory course that has been used to assist students in the arts-science transition. Finally, the performance of 'arts' students, in a physiology course over a 6-year period is described, analysed and discussed. The proposition emerges that arts students may be disadvantaged initially by having not only a lack of knowledge in physiology, but a different cognitive style to science specialists. The results of the students' examination performance over 6 years suggests that with the provision of only a limited amount of special help 'arts' students can perform as well as the 'science' students in physiology examinations. Other variables which may have contributed to this positive outcome are discussed.

Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system.

Techniques are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion.

The sodium and bicarbonate dependence of bile secretion in the guinea-pig.

The effects of the total substitution of sodium by lithium, and of bicarbonate by a mixture of chloride and phosphate, on the flow and composition of bile was studied in the isolated perfused guinea-pig liver using a single-pass perfusion system. 60% of secretion was bicarbonate dependent and 80% specifically required the presence of sodium. The secretion of bicarbonate in bile against a concentration gradient was inhibited by the presence of lithium. In contrast to the results of similar studies in the rat, lithium is not an effective substitute for sodium in maintaining bile secretion.

Uptake and action of a disulphonic stilbene (SITS) in the perfused guinea-pig liver: a comparison with bromsulphthalein.

1. Livers were perfused with a Krebs-Ringer bicarbonate buffer in a single-pass perfusion system. Bile secretion was maintained by infusion of secretin. 4-Acetamido-4'-isothiocyano-2,2'-stilbene disulphonic acid (SITS) was added to the perfusate to give concentrations ranging between 5 x 10(-6) and 10(-4) M. 2. SITS was extracted from the perfusate by the liver (V, 0 . 15 mumol/min per g liver; Km 8 . 6 x 10(-5) M) and excreted in bile in a modified form (bile/plasma ratio: 50-170; maximum rate of excretion: 25 nmol/min per g liver wet wt). 3. The rates of uptake and excretion of bromsulphthalein (BSP) were similar to those for SITS, with the exception that the affinity of BSP for hepatic uptake was greater (Km 1 . 8 x 10(-5) M). 4. Both SITS and BSP decreased the rate of bile flow. A 50% reduction in bile flow was attained in each case at an estimated drug content of the liver of 1 . 5 mumol/g wet wt. 5. Unlike other cells the hepatocyte appears to be readily penetrated by SITS, and it is suggested that SITS inhibits bile secretion by inhibiting an intracellular mechanism which could be mitochondrial in location.

An analysis of the choleretic effects of infusions of sodium cholate in the guinea-pig.

The choleretic effects of infusions of sodium cholate, with and without the simultaneous infusion of taurine was compared with the choleretic effect of infusions of sodium taurocholate at rates ranging from 20--70 nmole/min. g. liver in anaesthetized guinea-pigs. Sodium cholate was secreted in bile mainly conjugated with taurine and with glycine. 10% was secreted unconjugated. Not more than 10% of the total bile salts secreted may have undergone reduction at C-3. The increase in bile flow with sodium cholate was generally greater than that with sodium taurocholate. The additional flow could not be correlated with the presence of glycocholate or free cholate in bile, and may be due to an action of cholate on biliary secretory mechanisms before the bile salt is secreted into the canaliculi.

Effects of bile salts on the motor activity of the guinea-pig gall-bladder in vitro.

Intra-luminal pressures were measured in in vitro preparations of the guinea-pig gall bladder. Intrinsic tone and spontaneous activity were recorded together with the response of the gall-bladder to Pancreozymin. The effect of the presence of a variety of conjugated and unconjugated bile salts in the luminal fluid [pH 7.4] was studied. Sodium deoxycholate and sodium chenodeoxycholate had in inhibitory effect on motor activity at concentrations as low as 6.0 times 10(-6) mol. 1(-1) Sodium taurocholate at a concentration of 3 times 10(-3) mol. 1(-1) promoted regular spontaneous activity. The results are discussed in relation to their possible physiological, pathological and pharmacological implications.