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While carbon provides the basis for all of organic chemistry and biology, elemental carbon compounds themselves play vital roles in our world. Graphite, diamond, fullerenes, graphene, and amorphous carbon solids are used in myriad modern applications, and a number of new, metastable states of carbon with unusual and promising properties have recently been proposed and created. Furthermore, liquid carbon and warm dense carbon are of astrophysical interest, and been proposed to exist in the cores of large planets and stars (Ross, 1981) [1]. While much is known about the solid forms of carbon, its liquid state remains very poorly understood. Due to difficulties in preparing and studying this material, its structure and properties remain essentially unknown. In this review, we describe recent technological advances which have enabled new experiments on liquid carbon samples, prepared with laser melting and shock compression techniques.

We have examined the transmission of soft X-ray pulses from the FERMI free electron laser through carbon films of varying thickness, quantifying nonlinear effects of pulses above and below the carbon K-edge. At typical of soft X-ray free electron laser intensities, pulses exhibit linear absorption at photon energies above and below the K-edge, ∼308 and ∼260 eV, respectively; whereas two-photon absorption becomes significant slightly below the K-edge, ∼284.2 eV. The measured two-photon absorption cross section at 284.18 eV (∼6 × 10−48 cm4 s) is 7 orders of magnitude above what is expected from a simple theory based on hydrogen-like atoms - a result of resonance effects.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284  eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

The existence of liquid carbon as an intermediate phase preceding the formation of novel carbon materials has been a point of contention for several decades. Experimental observation of such a liquid state requires nonthermal melting of solid carbon materials at various laser fluences and pulse properties. Reflectivity experiments performed in the mid-1980s reached opposing conclusions regarding the metallic or insulating properties of the purported liquid state. Time-resolved X-ray absorption studies showed shortening of C-C bonds and increasing diffraction densities, thought to evidence a liquid or glassy carbon state, respectively. Nevertheless, none of these experiments provided information on the electronic structure of the proposed liquid state. Herein, we report the results of time-resolved resonant inelastic X-ray scattering (RIXS) and time-resolved X-ray emission spectroscopy (XES) studies on amorphous carbon (a-C) and ultrananocrystalline diamond (UNCD) as a function of delay time between the irradiating pulse and X-ray probe. For both a-C and UNCD, we attribute decreases in RIXS or XES signals to transition blocking, relaxation, and finally, ablation. Increased signal at 20 ps following the irradiation of the UNCD is attributed to the probable formation of nanoscale structures in the ablation plume. Differences in the amount of signal observed between a-C and UNCD are explained by the difference in sample thickness and, specifically, incomplete melting of the UNCD film. Comparisons to spectral simulations based on MD trajectories at extreme conditions indicate that the carbon state in our experiments is crystalline. Normal mode analysis confirmed that symmetrical bending or stretching of the C-C bonds in the diamond lattice results in XES spectra with small intensity differences. Overall, we observed no evidence of melting to a liquid state, as determined by the lack of changes in the spectral properties for up to 100 ps delays following the melting pulses.

Charge transport processes at interfaces play a crucial role in many processes. Here, the first soft x-ray second harmonic generation (SXR SHG) interfacial spectrum of a buried interface (boron-Parylene N) is reported. SXR SHG shows distinct spectral features that are not observed in x-ray absorption spectra, demonstrating its extraordinary interfacial sensitivity. Comparison to electronic structure calculations indicates a boron-organic separation distance of 1.9 Å, with changes of less than 1 Å resulting in easily detectable SXR SHG spectral shifts (ca. hundreds of milli-electron volts).

FlyFactorSurvey (http://pgfe.umassmed.edu/TFDBS/) is a database of DNA binding specificities for Drosophila transcription factors (TFs) primarily determined using the bacterial one-hybrid system. The database provides community access to over 400 recognition motifs and position weight matrices for over 200 TFs, including many unpublished motifs. Search tools and flat file downloads are provided to retrieve binding site information (as sequences, matrices and sequence logos) for individual TFs, groups of TFs or for all TFs with characterized binding specificities. Linked analysis tools allow users to identify motifs within our database that share similarity to a query matrix or to view the distribution of occurrences of an individual motif throughout the Drosophila genome. Together, this database and its associated tools provide computational and experimental biologists with resources to predict interactions between Drosophila TFs and target cis-regulatory sequences.

Background: The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect., Methods: Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults., Results: Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05)., Conclusions: The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium, and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which Hofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of speculation, and this, coupled with the fact that atracurium is a mixture of 10 isomers, has led to the development of many innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis-isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent volume of distribution and an elimination half-time similar to that of pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two isomers of mivacurium are very similar, whereas the third isomer differs greatly in both pharmacological activity and elimination half-time, so that analysis requires complex pharmacokinetic methods.

We describe a method of recording pharmacological responses in isolated arterial segments, based on the direct measurement of vascular wall elastance. The segment outflow is intermittently occluded, and the elastance determined from the subsequent pressure-flow relationship. Since the measurement cycle can be repeated 12 times per minute, rapid pharmacological responses can be studied. The method is capable of demonstrating a sigmoid dose-response relationship to noradrenaline added to the perfusate.

The Maillard or browning reaction between reducing sugars and protein contributes to the chemical deterioration and loss of nutritional value of proteins during food processing and storage. This article presents and discusses evidence that the Maillard reaction is also involved in the chemical aging of long-lived proteins in human tissues. While the concentration of the Amadori adduct of glucose to lens protein and skin collagen is relatively constant with age, products of sequential glycation and oxidation of protein, termed glycoxidation products, accumulate in these long-lived proteins with advancing age and at an accelerated rate in diabetes. Among these products are the chemically modified amino acids, N epsilon-(carboxymethyl)lysine (CML), N epsilon-(carboxymethyl)hydroxylysine (CMhL), and the fluorescent crosslink, pentosidine. While these glycoxidation products are present at only trace levels in tissue proteins, there is strong evidence for the presence of other browning products which remain to be characterized. Mechanisms for detoxifying reactive intermediates in the Maillard reaction and catabolism of extensively browned proteins are also discussed, along with recent approaches for therapeutic modulation of advanced stages of the Maillard reaction.

The effects of age on the pharmacokinetics of pancuronium were investigated. The distribution volume of pancuronium did not appear to be age-dependent, but elimination of the drug decreased with increasing age. The clinical implications of these findings are discussed.

Alfentanil 700 micrograms and fentanyl 100 micrograms were compared as anaesthetic adjuvants in 90 patients undergoing short duration gynaecological procedures. The results show that, at the chosen dose ratio, alfentanil causes a higher frequency of post-induction apnoea, but thereafter the respiratory effects of the two drugs were comparable. No differences in incremental requirements or evoked movements were found. Among patients who had been given ergometrine, the alfentanil group suffered a greater frequency of nausea and vomiting in the period immediately after operation. It is concluded that in single i.v. doses, alfentanil 700 micrograms is more potent than fentanyl 100 micrograms. Moreover, the results suggest that, unlike fentanyl, this very short acting agent would be used to greater effect if given in divided doses during surgery.

Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.

Unless patients harbouring this uncommon tumour are correctly prepared and protected from the effects of excessive catecholamine release, they are greatly at risk when undergoing surgical procedures of any kind. This short review describes the clinical syndromes associated with phaeochromocytoma, the diagnostic procedures which may identify and localize the tumour(s), the principles and practical aspects of pharmacological control, and a method of anaesthetic management which has proved safe and effective in many patients.

The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte:plasma partition, and heptane:water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes. It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.

Hemocytes of Biomphalaria glabrata mediate the internal defensive response which, in resistant snail strains, kills sporocysts of Schistosoma mansoni. Lacking a gut, the sporocyst has only its tegument to interact with the host milieu (hemolymph). We have, therefore, focused our study on the surface-exposed proteins of hemocytes and sporocyst tegument. Using gentle biotinylation of living systems, labelled proteins were studied after SDS-PAGE electrophoresis and transfer to nitrocellulose. Results validate the utility of surface biotinylation in studies of host and parasite interfaces. A low diversity characterizes hemocyte surfaces and strain-specific differences are not in evidence. Hemocyte surfaces differ distinctly from the plasma in which these cells reside. In contrast, sporocyst surfaces expose a wide variety of peptides. These are remarkably stable even when sporocysts procured in snail plasma-free media are exposed to plasma. Thus, antigenic differences seen previously when Western immunoblotting was used to study sporocyst surfaces appear to be manifestations of minor changes in the exposed peptides or changes not detectable with this methodology. Hemoglobin, acquired by sporocysts from snail plasma, is processed and disappears from the surface during an overnight chase in culture medium.

It has been demonstrated that a simple two-compartment kinetic model may account for the changes in plasma concentration of pancuronium after i.v. administration. However, it can be shown that this simple model does not account satisfactory for the observed changes in muscle twitch response. By the addition of a receptor (biophase) compartment, twitch response can be reconciled with model behavior and the characteristics resemble those predicted by animal studies. The complete model is applied to the problem of total renal failure, and shows that patients with this condition are likely to be marginally resistant to small doses of pancuronium, with a normal rate of recovery. However, larger doses are likely to result in delayed recovery, the duration of effect increasing in a dose-dependent manner.

Alfentanil 35 micrograms kg-1, was used successfully in a patient with severe aortic stenosis, in order to minimize the haemodynamic responses to intubation and surgery during Caesarean section. The baby was delivered apnoeic, unresponsive and with poor muscle tone, but responded rapidly to naloxone. Plasma alfentanil concentrations and percentage binding to plasma proteins were measured in both maternal and neonatal blood. Free drug concentrations were similar in both mother and neonate, but maternal plasma proteins had a higher affinity for alfentanil. Only 67.26% of neonatal plasma alfentanil was bound to plasma protein. This value did not differ significantly from those estimated from the blood of a further 12 healthy neonates.

Propofol was used to induce and maintain anaesthesia in patients undergoing minor gynaecological procedures. Quality of anaesthesia, the rate of recovery and the influence of different methods of premedication were assessed. Unpremedicated patients required a higher induction dose than those premedicated with either lorazepam or papaveretum and hyoscine, but maintenance dose requirements were comparable. Regardless of premedication, there were similar decreases in mean arterial pressure, although respiratory function recovered more rapidly in patients premedicated with lorazepam. No significant changes in heart rate were noted in any group. The overall incidence of pain on injection was 3.7% (lignocaine 0.5 mg added to each 9.5 mg of propofol) and a skin rash occurred in 6% of patients. All patients recovered rapidly and uneventfully.

The effects of diamorphine hydrochloride 0.1 mg/kg, given either extradurally or intramuscularly for postoperative analgesia were compared in two randomised double-blind studies involving 39 patients undergoing thoracotomy and major gynaecological surgery. Assessments were made at fixed intervals after the administration of diamorphine and consisted of the measurement of pain or analgesic effect. Segmental, sympathetic and any adverse effects were sought. There was no significant difference in the quality of analgesia between the two groups in either trial. Extradural diamorphine provided safe and effective analgesia of rapid onset, with no specific undesirable side-effects. In both studies, analgesia was more prolonged following extradural administration. The relative proportion of spinal binding may be increased after extradural administration and this may be reflected in the prolonged analgesia observed.

The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed, and artificially ventilated dogs. In one group, a bolus of 100 micrograms/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min, and recovery occurred within 90 min. A second group was given increasing bolus doses of fentanyl from 1.5 to 100 micrograms/kg every 20 min for 200 min. The doses and intervals were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 micrograms/kg and were predicted by a two-compartment pharmacokinetic model derived from data of the first group. In the second group, the bolus dose of 100 micrograms/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 micrograms/kg dose. An additional bolus dose of 100 micrograms/kg given 2 h after the first did not depress the evoked reflexes below the control values. It was concluded that tolerance to the effects of fentanyl can occur within 3 h and that for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min.

Antibodies to group A streptococcal carbohydrate, demonstrable by radioimmunoassay, were elicited in Pacific hagfish, Eptatretus stoutii, after prolonged immunization with whole cell vaccine. This hagfish antibody, isolated by ion-exchange chromatography of immune serum, exhibited a single precipitin line after immunoelectrophoresis against rabbit antiserum to hagfish serum. The isolated antibodies retained high binding activity for the streptococcal carbohydrate, but lacked the natural hemagglutinating activity found in both nonimmune and immune sera. Analysis by gel filtration in neutral and dissociating buffers and by sodium dodecyl sulfate/polyacrylamide gel electrophoresis under nonreducing conditions indicated an intact molecule of molecular weight approximately 160,000 that may be noncovalently associated in a polymer of higher molecular weight. Heavy chains of mobility identical to that of murine mu chains and light chains of mobility significantly slower than murine lambda chains were obtained after sodium dodecyl sulfate gel electrophoresis under reducing conditions. Instability of the tertiary structure of the antibody molecule was indicated by partial dissociation in buffers containing sodium dodecyl sulfate and by dissociation at low concentrations of reducing agent. In contrast to its well-developed system of cell-mediated immunity, only a minimal system of circulating antibody production is evident in this primitive fish. No evidence for divergence of cyclostome lymphocytes into separate T- and B-cell systems has yet been discerned.

A demand analgesia apparatus is described. It communicates with the patient by means of spoken messages in any desired language, so that preliminary instruction is unnecessary. Dosage is limited by a reduction in respiratory rate, and by a series of electronic fail-safe circuits. Operation of the system is illustrated in a series of 10 patients given fentanyl "on demand" for the first 12 h after operation. The mean dose rate 0.73 +/- 0.49 microgram min-1. There was no evidence of cumulation or tolerance during the period of study.

A case-control study of lung cancer in white male welders was undertaken to investigate possible environmental and occupational causes of a 50% excess of lung cancer observed in this occupational group. The subjects were identified from a population-based cancer registry in Los Angeles County. A standardized questionnaire was administered to either subjects or proxy informants of 90 lung cancer cases and 116 non-lung-cancer controls. Significantly increased risks of lung cancer were associated with tobacco smoking (odds ratio 7.6, p less than .005) and shipyard welding with at least a 10-year latency since first exposure (odds ratio 1.7, p less than .05). Although there were elevated risks associated with some specific welding processes, none were statistically significant. Control subjects were more likely to have had exposure to confined-space welding (odds ratio 0.6, 95% CI = 0.3-1.2), and this association was greatest where there had been at least a 20-year latency since first exposure (0.5, 95% CI = 0.3-1.0). We conclude that the excess of lung cancer in this welding population is contributed to by a higher frequency of smoking and probable exposure to asbestos in shipyards. Other factors may be important, but probably because of limited power and reliance on proxy information, this study failed to detect other statistically significant risks.

In vitro phagocytosis of yeast cells by hemocytes of the mollusc Biomphalaria glabrata can occur in the absence of plasma, but is enhanced by opsonization in plasma from certain snail strains. We have investigated the carbohydrate specificity of the hemocyte-bound receptor for phagocytosis and the free plasma opsonin using two dominant carbohydrate components of the yeast cell wall (laminarin and mannan). Phagocytic uptake in the absence of plasma of both untreated and opsonized yeast is strongly inhibited by laminarin, but is unaffected by mannan. In contrast, laminarin does not interfere with opsonization whereas mannan blocks the process, blocking the binding of a 57 kD plasma component as detected by Western immunoblot. These results suggest that the opsonic lectin in plasma is not simply a free form of the hemocyte-bound receptor for yeast phagocytosis.

The Amadori Rearrangement Product is the first stable adduct formed during glycation (nonenzymatic glycosylation) of protein. This review deals with the structure of the Amadori adduct on protein, factors affecting the kinetics and specificity of glycation of protein, measurements of the extent of glycation of proteins in vivo, and the possible significance of glycation itself, versus post-glycation reactions, in the development of pathophysiology in diabetes.

After i.v. administration, the distribution and elimination of many drugs may be simulated by a compartmental mathematical model. The analogue can be used to construct such models in electrical terms. When programmed with an appropriate model, the analogue can be used in a wide range of predictive studies. The application of the analogue is illustrated by analysis of serial plasma concentrations of fentanyl and pancuronium.