It has been established previously that the maintenance of expression of prespore-specific genes of Dictyostelium discoideum is prevented by the translational inhibitor cycloheximide. The drug had no ...effect upon the level of trascripts of the other genes examined, prestalk-specific or cell type non-specific (Mehdy, M., Ratner, D. and Firtel, R., (1983) Cell 32, 763-771). We have now characterized the cellular specificity and temporal profiles of mRNA accumulation of additional Dictyostelium cDNA clones. Other inhibitors of in vivo protein synthesis have been examined, with emetine shown to be a particularly effective but reversible agent. Four structurally and mechanistically distinct translational inhibitors each prevented the reaccumulation of prespore transcripts in cyclic AMP-primed disaggregated amoebae. These results establish a role for protein synthesis in the transcription or transcript stability of prespore genes.
Tendon transfer surgery has evolved over the past decade. Unique muscle properties have been elucidated in terms of potential force generation, excursion, and metabolic properties. The choice of an ...appropriate donor muscle is becoming more of a science than an art. The measurement of sarcomere length has progressed from the laboratory into surgery. Methods of tendon coaptation have advanced to allow early mobilization. This article reviews recent advances in our understanding of tendon transfer surgery of the hand and upper extremity.
Abstract Objective: The aim of this study was to examine the glucose-lowering effect of exenatide over 24 hours in patients with type 2 diabetes with inadequate glycemic control using metformin, with ...or without a thiazolidinedione (TZD). Methods: This randomized, double-blind, 2-arm, parallel-group, placebo-controlled, 2-week study was conducted in patients with type 2 diabetes with inadequate glycemic control, despite metformin with or without a TZD. Patients underwent a baseline and a week-2 (study end) 24-hour admission during which serial serum glucose measurements were taken. Preprandial and postprandial concentrations of triglycerides and free fatty acids were also measured. Meals provided for each patient were identical at the baseline and week-2 assessments. Following the baseline admission, patients were randomized to receive SC injections of either exenatide (5 μg BID for 1 week, then 10 μg BID for the next week) or placebo (volume equivalent) for 14 days. Results: A total of 30 patients (19 women 63%, 11 men 37%; mean SD age, 52.6 11.2 years; weight, 94.3 23.0 kg; body mass index, 34.2 6.1 kg/m2 ; glycosylated hemoglobin value, 8.0% 0.9%; diabetes duration, 8.7 5.6 years; race, Hispanic 18 60%, white 10 33%, black 2 7%) were eligible. Seventeen patients (57%) were randomized to treatment with exenatide and 13 patients (43%) received placebo. Concurrent antidiabetic medications were metformin only (n = 19 63%) and metformin plus a TZD (n = 11 37%). All postbaseline values were least squares mean (SE). After 2 weeks (study end), the 24-hour time-average glucose values were 7.0 (0.2) and 8.8 (0.3) mmol/L for exenatide-treated and placeboadministered patients, respectively ( P < 0.001). The glucose values for patients treated with exenatide were lower compared with those in patients who received placebo 2 hours after the morning meal (6.6 0.4 vs 12.0 0.5 mmol/L; P < 0.001), the midday meal (8.8 0.5 vs 11.8 0.6 mmol/L; P = 0.001), and the evening meal (6.8 0.4 vs 11.3 0.4 mmol/L; P < 0.001). The mean durations of patient exposure to glucose concentrations >7.8 and >11.1 mmol/L were significantly shorter for the exenatide group compared with the placebo group (>7.8 mmol/L: 6.8 0.9 vs 14.1 1.1 hours; >11.1 mmol/L: 1.0 0.7 vs 4.7 0.8 hours; both, P < 0.001). After 2 weeks, the postprandial triglyceride excursions after the morning and evening meals for patients treated with exenatide were significantly lower compared with those treated with placebo. There was no apparent effect on free fatty acid concentrations. Conclusions: In these patients with type 2 diabetes, exenatide was associated with significantly reduced glucose concentrations at multiple time points during 24 hours, with the greatest effect seen on postprandial glucose concentrations. In addition, exenatide was associated with decreased overall hyperglycemic exposure and significantly decreased postprandial triglyceride excursions. These results are consistent with those seen in other studies that reported the effectiveness of exenatide in controlling hyperglycemia in patients with type 2 diabetes.
Laser Phase Errors in Seeded FELs Ratner, D.; Fry, A.; Stupakov, G. ...
Physical review special topics. PRST-AB. Accelerators and beams,
03/2012, Letnik:
15, Številka:
3
Journal Article
Odprti dostop
Harmonic seeding of free electron lasers has attracted significant attention from the promise of transform-limited pulses in the soft X-ray region. Harmonic multiplication schemes extend seeding to ...shorter wavelengths, but also amplify the spectral phase errors of the initial seed laser, and may degrade the pulse quality. In this paper we consider the effect of seed laser phase errors in high gain harmonic generation and echo-enabled harmonic generation. We use simulations to confirm analytical results for the case of linearly chirped seed lasers, and extend the results for arbitrary seed laser envelope and phase.
One of the principal challenges for the long-term implantation of biosensors is that the normal physiological response of the body creates a fibrotic capsule of scar tissue surrounding the implanted ...sensor (the foreign body response). This dense, collagenous capsule isolates the device from the local environment, causing a time-dependent degradation of the signal. We utilize this degradation or change to an electrical signal as an indicator of the physiological responses to the implantation of the biomaterial device. We thus track the foreign body response electronically, an important analytical method for our program that aims to reduce the foreign body response. We applied electrical impedance spectroscopy (EIS) to track changes of the electrical signal behavior over time between micro-electrode arrays. We have performed experiments both in vitro and ex ova. In vitro, we used a reservoir of phosphate buffered saline into which selected proteins were introduced that adsorb onto the electrode surface. Three proteins were studied and each was found to affect the EIS results differently. We have investigated the foreign body response ex ova using the chick chorio-allantoic membrane (CAM) model. Following implantation of the electrode array the chick CAM exhibited a response similar to the mammalian foreign body response. We report that the electrical signal degrades with tissue growth during the healing and remodeling following the traumatic implantation of the electrode needle through the ectoderm side of the CAM tissue.
Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted plasmid insertion events involving the ends of transforming DNA molecules. These undesirable and often ...multiple insertions occur both randomly (i.e. non-homologously) and at the targeted locus. By blocking the 3′ ends of transforming DNA with 2′3′ dideoxynucleotides, we have reduced the frequency of end-mediated DNA insertion in
Dictyostelium amoebae. As a result, only one copy of the selectable gene is introduced at the target locus to achieve a precise gene disruption.
The development of membranes that swell in response to glucose is reported. The membranes may prove to be useful in glucose monitoring or glucose-dependent insulin delivery. The polymers were ...synthesized by the radiation-induced polymerization of frozen solutions containing hydroxyethylmethacrylate, N,N-dimethylaminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and glucose oxidase. The polymers were hydrogels, with water contents in the range of 60-90%, depending on the pH or glucose concentration. Changes in swelling and permeability of the hydrogel were caused by exposure to glucose solutions. The gluconic acid formed by the glucose oxidase catalyzed oxidation of glucose in the membrane lowered the pH of the system and thus caused the changes in the membrane. The retention of enzyme activity by the membranes in vitro and in vivo is also reported. The large differences in properties among membranes made with different chemical formulations suggest that glucose-sensitive membranes with performance characteristics needed for an artificial pancreas may be an achievable goal.
The adsorption of bovine serum albumin from flowing solutions onto germanium and three polyetherurethanes varying in soft segment content was studied by a Fourier transform infrared/attenuated total ...reflectance technique. Spectral differences observed in the amide I, II, and III regions upon adsorption to all four surfaces were consistent with a loss of helix and gain of beta-structure. There appeared to be a slight difference between BSA adsorbed to germanium and the PEUs, but no distinction could be made between BSA adsorbed to the different PEUs.
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