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Optimal photon energies for IUdR K-edge radiosensitization with filtered x-ray and radioisotope sources.

The purpose of this work is to determine the most physically effective radiation energy for K-edge absorption of x- or gamma-rays by iododeoxyuridine (IUdR) on Chinese hamster ovary (CHO) cells. Brachytherapy sources (Sm-145, I-125, Yb-169 and Am-241) and x-ray beams (30 kVp, 100 kVp and 100 kVp with gold, gadolinium, lead or tungsten filtration) were investigated for their preferential absorption qualities by IUdR sensitized DNA. The 30 kVp, 100 kVp and 100 kVp with tungsten filtration were then used to irradiate CHO cells, with or without IUdR incorporation (i.e. 10(-5) M of IUdR for 3 days). Radiation absorption calculations were performed to determine the increase in energy absorption in DNA with and without IUdR incorporated. In order to measure the in vitro biological effects of K-edge absorption, cell survival experiments were performed. The radiation physics calculations yielded an iodine dose enhancement ratio (DER) of 1.4+/-0.15. 1.8+/-0.15 and 2.7+/-0.15 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for 18% IUdR replacement of thymidine in DNA. The corresponding cell sensitization enhancement ratios (SER), determined from the cell survival assay, were determined to be 1.24+/-0.2, 1.8+/-0.2 and 2.3+/-0.3 for the 30 kVp, 100 kVp and tungsten filtered 100 kVp respectively, for cells with 18+/-2% IUdR incorporation. These SER values are in reasonable agreement with the DER values of 1.4, 1.8 and 2.7. From these radiation calculations and radiobiology experiments we confirm that using x-radiation energies above the K-edge of iodine (33.2 keV) can have a significant effect on cell survival. This effect is due mainly to the increase in the local dose to the DNA for IUdR-sensitized cells compared with the normal DNA which lacks the iodine contrast agent. Our results support the clinical application of IUdR and low-energy brachytherapy, perhaps using new technologies such as the x-ray needle or new isotopes such as Yb-169.

Americium↗

[Optimization of energy parameters of ultrasound and laser cataract surgery with a preliminary transcorneal endocapsular YAG-laser impact exerted on the cataract lens nuclei].

The values of the main energy and time parameters of ultrasound and laser fragmentation of different-hardness cataract-lens nuclei were analyzed in patients of various age groups after a preliminary transcorneal endocapsular YAG-laser treatment of the lens. The results show, in all cases, lower key energy and time characteristics, which primarily concerns a total energy index of the ultrasound and laser effect of no less than 20% versus the ordinarily used parameters.

Adult↗

Theoretical optimization of a split septaless xenon ionization detector for dual-energy chest radiography.

It is proposed that digital scanned projection radiography of the chest be performed by using an energy-sensitive septaless xenon ionization detector (SXID) to obtain dual-energy images. The proposed detector is composed of a front region, sensitive to low-energy x rays, and a rear region, sensitive to high-energy x rays, separated by a suitable filter layer. We have developed a simple, precise theoretical formulation for dual-energy optimization, and applied it to the split SXID. We describe the variation of optimum detector performance with source kilovoltage and filtration (material and thickness), and hence heat loading, under conditions of constant exposure and constant dose. We estimate dose as the average absorbed dose to an equivalent water layer of suitable thickness, assuming slab geometry, so that the calculation is as simple as that for exposure.

Humans↗

Energy-conformation studies of frequency of beta-turns in tetrapeptide sequences.

The optimized energies of seven beta-bends, repeating C5 and C7, and right- and left-handed alpha-helical conformations for each of eight tetrapeptides have been computed using empirical methods. Eight tetramers were selected: four helix-forming sequences with hydrophobic residues such as Val, Leu, Ile and Trp, and four helix-breaking sequences with hydrophilic residues such as Asp, Asn and Ser, as determined by their frequency of occurrence in beta turns in proteins. Analysis of the optimized conformations with energies less than or equal to 2.1 kcal/mol from the absolute minimum energy conformer for each tetramer reveals a correlation between low-energy conformations and those predicted from observed protein structures. These results show that energy calculations on small peptide fragments may be usefulin predicting protein structure.

Amino Acid Sequence↗

Energy- and intensity-modulated electron beams for radiotherapy.

This work investigates the feasibility of optimizing energy- and intensity-modulated electron beams for radiation therapy. A multileaf collimator (MLC) specially designed for modulated electron radiotherapy (MERT) was investigated both experimentally and by Monte Carlo simulations. An inverse-planning system based on Monte Carlo dose calculations was developed to optimize electron beam energy and intensity to achieve dose conformity for target volumes near the surface. The results showed that an MLC with 5 mm leaf widths could produce complex field shapes for MERT. Electron intra- and inter-leaf leakage had negligible effects on the dose distributions delivered with the MLC, even at shallow depths. Focused leaf ends reduced the electron scattering contributions to the dose compared with straight leaf ends. As anticipated, moving the MLC position toward the patient surface reduced the penumbra significantly. There were significant differences in the beamlet distributions calculated by an analytic 3-D pencil beam algorithm and the Monte Carlo method. The Monte Carlo calculated beamlet distributions were essential to the accuracy of the MERT dose distribution in cases involving large air gaps, oblique incidence and heterogeneous treatment targets (at the tissue-bone and bone-lung interfaces). To demonstrate the potential of MERT for target dose coverage and normal tissue sparing for treatment of superficial targets, treatment plans for a hypothetical treatment were compared using photon beams and MERT.

Algorithms↗

Aspects on the optimal photon beam energy for radiation therapy.

The selection of optimal photon beam energy is investigated both for realistic clinical bremsstrahlung beams and for monoenergetic photon beams. The photon energies covered in this investigation range from 60Co to bremsstrahlung and monoenergetic beams with maximum energies up to 50 MeV. One head and neck tumor and an advanced cervix tumor are investigated and the influence of beam direction is considered. It is shown that the use of optimized intensity modulated photon beams significantly reduces the need of beam energy selection. The most suitable single accelerator potential will generally be in the range 6-15 MV for both superficially located and deep-seated targets, provided intensity-modulated dose delivery is employed. It is also shown that a narrow penumbra region of a photon beam ideally should contain low-energy photons (< or =4 MV), whereas the gross tumor volume, particularly when deep-seated targets are concerned, should be irradiated by high-energy photons. The regions where low photon energies are most beneficial are where organs at risk are laterally close to the target volume. The situation is completely changed when uniform or wedged beams are used. The selection of optimal beam energy then becomes a very important task in line with the experience from traditional treatment techniques. However, even with a large number of uniform beam portals, the treatment outcome is substantially lower than with a few optimized intensity-modulated beams.

Female↗

Energy requirements of children with cerebral palsy.

Energy requirements of children and adolescents with cerebral palsy appear to be disease-specific and different from the current recommendations for healthy children, varying depending upon functional capacity, degree of mobility, severity of disease, and level of altered metabolism. Feeding problems are prevalent in many of these children, and can result in inadequate energy intake. Wasting of voluntary muscles, a common symptom of cerebral palsy, contributes to reduced resting energy needs; nevertheless, the location of the central nervous system lesion may also influence energy requirements. To guarantee individualized, accurate, and optimal energy recommendations for this population, resting energy expenditure should preferentially be measured by indirect calorimetry. Equations and formulae to predict healthy people's resting energy expenditure are available, but tend to overestimate these children's energy needs. Future studies should address the role of the central nervous system in regulating energy metabolism in this population. When adequately nourished, children and adolescents with cerebral palsy appear more tranquil and require decreased feeding time, which gives caregivers time to develop the child's functional independence and character. Understanding energy requirements of this population will provide caregivers and health professionals with guidelines for providing optimal nutritional status.

Basal Metabolism↗

Optimal allocation of energy to growth and reproduction.

The optimal allocation of energy to growth and reproduction is considered for three different cases, i.e., a single reproduction (semelparity), reproduction through repeated discrete clutches, and continuous reproduction. The problem reduces to optimizing age and size at maturity. The best strategy is to continue growth until the change of production rate with respect to increasing body size, multiplied by life expectancy for those attaining adulthood and reproducing successfully, is greater than one. The time at which semelparous species reproduce may also be optimized; for the other modes of reproduction only physiological factors or seasonality can limit the maximum age. A brief growing season or high mortality rate are factors leading to early maturity and small adult body size.

Animals↗

Unified optimization criterion for energy converters.

We propose a unified optimization criterion for energy converters. It represents the best compromise between energy benefits and losses for a specific job and neither an explicit evaluation of entropies nor the consideration of environmental parameters are required. For all considered systems the criterion predicts a performance regime laying between those of maximum efficiency and maximum useful energy. Such regime has been invoked as optimum not only in macroscopic heat engines but also in some molecular motors.

Journal Article↗

[Potassium channel activators: comparative structural study of pinacidil, diazoxide and cromakalim].

A conformational analysis has been performed with SYBYL starting from the energy optimized (Tripos force field) X-ray conformation of (R,S)-pinacidil. The geometry of four selected low energy conformers has been reoptimized using the AM1 semiempirical Molecular Orbital method (MOPAC 5.0), and the total energy of the optimized conformers has been compared. In spite of an apparent structural dissimilarity, a good analogy has been found between the calculated isopotential map of diazoxide and that of at least one selected low energy conformer of pinacidil. It has been suggested that, unlike cromakalim, the low but observable activity of pinacidil on pancreatic B-cells could be explained by adoption for this compound of a conformation having a diazoxide-like stereoelectronical imprint which could assume a similar interaction on the same biological receptor.

Antihypertensive Agents↗

A comparison of 50-J versus 100-J shocks for direct-current cardioversion of atrial flutter.

BACKGROUND: Direct-current cardioversion remains the gold standard for restoration of sinus rhythm in patients with atrial flutter. Although an initial energy of 50 J is recommended, the optimal energy settings have not been evaluated in a large series of contemporary patients. METHODS: We compared the outcome of cardioversion with 50 J versus 100 J in 330 consecutive patients with atrial flutter. Initial energy was based on attending physician preference. One hundred sixty patients received 50 J and 170 patients received 100 J. RESULTS: Patients in both groups did not differ significantly in age, sex, weight, body mass index, duration of the arrhythmia, postoperative status, presence and type of structural heart disease, or use of antiarrhythmic drugs. Patients in the 100-J group had more first shock conversion (85% vs 70%; P =. 001), fewer total shocks (1.2 +/- 0.5 vs 1.4 +/- 0.7; P =.001), and less induction of atrial fibrillation (2% vs 11%; P =.002). There were no significant differences in overall restoration of sinus rhythm, cumulative energy delivered, anesthetic dose, and procedure room time. On multivariate analysis, delivery of 100 J was the strongest predictor of first shock success (odds ratio 2.6, 95% confidence interval 2.13 to 3.16; P <.001). CONCLUSION: An initial energy of 100 J is more efficient for restoration of sinus rhythm in patients with atrial flutter.

Aged↗

Associative memory hamiltonians for structure prediction without homology: alpha-helical proteins.

Energy landscape theory is used to obtain optimized energy functions for predicting protein structure, without using homology information. At short sequence separation the energy functions are associative memory Hamiltonians constructed from a database of folding patterns in nonhomologous proteins and at large separations they have the form of simple pair potentials. The lowest energy minima provide reasonably accurate tertiary structures even though no homologous proteins are included in the construction of the Hamiltonian. We also quantify the funnel-like nature of these energy functions by using free energy profiles obtained by the multiple histogram method.

Computer Simulation↗

Nitric oxide signaling: systems integration of oxygen balance in defense of cell integrity.

PURPOSE OF REVIEW: Nitric oxide has emerged as a ubiquitous signaling molecule subserving diverse pathophysiologic processes, including cardiovascular homeostasis and its decompensation in atherogenesis. Recent insights into molecular mechanisms regulating nitric oxide generation and the rich diversity of mechanisms by which it propagates signals reveal the role of this simple gas as a principle mediator of systems integration of oxygen balance. RECENT FINDINGS: The molecular lexicon by which nitric oxide propagates signals encompasses the elements of posttranslational modification of proteins by redox-based nitrosylation of transition metal centers and free thiols. Spatial and temporal precision and specificity of signal initiation, amplification, and propagation are orchestrated by dynamic assembly of supramolecular complexes coupling nitric oxide production to upstream and downstream components in specific subcellular compartments. The concept of local paracrine signaling by nitric oxide over subcellular distances for short durations has expanded to include endocrine-like effects over anatomic spatial and temporal scales. From these insights emerges a role for nitric oxide in integrating system responses controlling oxygen supply and demand to defend cell integrity in the face of ischemic challenge. In this context, nitric oxide coordinates the respiratory cycle to acquire and deliver oxygen to target tissues by regulating hemoglobin function and vascular smooth muscle contractility and matches energy supply and demand by down-regulating energy-requiring functions while shifting metabolism to optimize energy production. SUMMARY: Insights into mechanisms regulating nitric oxide production and signaling and their integration into responses mediating homeostasis place into specific relief the role of those processes in pathophysiology. Indeed, endothelial dysfunction associated with altered production of nitric oxide regulating tissue integrity contributes to the pathogenesis underlying atherogenesis. Moreover, this central role in pathophysiology identifies nitric oxide signaling as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with ischemic cardiovascular disease.

Animals↗

Nutritional supplementation decreases hip fracture-related complications.

Protein energy malnutrition is an important determinant of clinical outcome in older patients after hip fracture, but the effectiveness of nutritional support programs in routine clinical practice is controversial. We performed a prospective, randomized, controlled clinical trial to determine if nutritional supplementation decreased fracture-related complications in a selection of otherwise healthy patients with hip fractures. Patients were randomized to intervention or control groups. The control group (n = 40) was given ordinary hospital food and beverage. The intervention group (n = 40) also was administered a 1000 kcal daily intravenous supplement for 3 days, followed by a 400 kcal oral nutritional supplement for 7 days. We recorded daily fluid and energy intake during the first 10 days of hospitalization and fracture-related complications up to 4 months. The total fluid and energy intake in the intervention group neared optimal levels. The control group received 54% and 64% of optimal energy and fluid intake, respectively. The risk of fracture- related complications was greater in the control group (70%) than in the intervention group (15%). Four patients in the control group died within 120 days postoperatively. The comprehensive balanced nutrition supplement resulted in lower complication rates and mortality at 120 days postoperatively.

Administration, Oral↗