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Results for “parameter optimization”

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PubMed2001

Assessment of axillary lymph node involvement in small breast cancer: analysis of 893 cases.

Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.

Adult↗

PubMed1994

The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures.

A method for kinetic analysis of dynamic positron emission tomography (PET) data by linear programming that allows identification of the components of a measured PET signal without predefining a compartmental model has recently been proposed by Cunningham and co-workers. The method identifies a small subset of functions from a large input set of feasible functions that best fits the time course of total radioactivity measured by PET. To investigate in detail the properties of this technique, we applied it to PET studies with [18F]fluorodeoxyglucose, a tracer with well-characterized kinetic properties. We examined dynamically acquired data over various time intervals in many brain regions and found that the number of components identified by the method is stable and consistent with the presence of kinetic heterogeneity in every region. We optimized the method for determination of regional rates of glucose utilization; calculated rates were found to be somewhat dependent upon the treatment of noise in the measured tissue data and upon the time interval in which the data were collected. The application of a numerical filter to remove noise in the data resulted in values for regional cerebral glucose utilization that were stable with time and consistent with rates determined by the other established techniques. Based on the results of the current study, we expect that the spectral analysis technique will prove to be a highly flexible tool for kinetic analysis of other tracer compounds; it is capable of producing low-variance, time-stable estimates of physiological parameters when optimized for time interval of application, input spectrum of components, and processing of noise in the data.

Adult↗

PubMed2006

Mathematical models of proprioceptors. I. Control and transduction in the muscle spindle.

We constructed a physiologically realistic model of a lower-limb, mammalian muscle spindle composed of mathematical elements closely related to the anatomical components found in the biological spindle. The spindle model incorporates three nonlinear intrafusal fiber models (bag(1), bag(2), and chain) that contribute variously to action potential generation of primary and secondary afferents. A single set of model parameters was optimized on a number of data sets collected from feline soleus muscle, accounting accurately for afferent activity during a variety of ramp, triangular, and sinusoidal stretches. We also incorporated the different temporal properties of fusimotor activation as observed in the twitchlike chain fibers versus the toniclike bag fibers. The model captures the spindle's behavior both in the absence of fusimotor stimulation and during activation of static or dynamic fusimotor efferents. In the case of simultaneous static and dynamic fusimotor efferent stimulation, we demonstrated the importance of including the experimentally observed effect of partial occlusion. The model was validated against data that originated from the cat's medial gastrocnemius muscle and were different from the data used for the parameter determination purposes. The validation record included recently published experiments in which fusimotor efferent and spindle afferent activities were recorded simultaneously during decerebrate locomotion in the cat. This model will be useful in understanding the role of the muscle spindle and its fusimotor control during both natural and pathological motor behavior.

Action Potentials↗

PubMed2002

Coagulation index to distinguish severe preeclampsia from normal pregnancy.

The purpose of this study was to establish a new coagulation index to distinguish severe preeclampsia from normal pregnancy using optimal coagulation parameters. The difference between platelet counts in early gestation and before delivery (DeltaPlt = [platelet counts before delivery] - [platelet counts in early gestation]) was calculated as an index of changes in platelet counts. Antithrombin (AT) activity, thrombin-antithrombin (TAT) complex, fibrin degradation products (FDP) D-dimer, and DeltaPlt were investigated in 72 cases of normal pregnant women in the third trimester of pregnancy and 56 cases of severe preeclampsia. The new coagulation index was calculated using multivariate logistic regression analysis. As a result, in a case using four parameters, the following formula was obtained: Y = (-0.019 x AT activity) + (0.067 x TAT) + (0.067 x D-dimer) + (-0.064 x DeltaPlt) + 0.706. According to this formula, coagulation indices in normal pregnant women and in patients with severe preeclampsia were -0.77 +/- 0.51 and 1.41 +/- 1.56, respectively (p < 0.0001). Among patients with severe preeclampsia, coagulation and fibrinolysis disorders before delivery were typical in patients terminated by cesarean section (coagulation index = 1.62 +/- 1.66) compared with those with successful vaginal delivery (coagulation index = 0.52 +/- 0.34) (p < 0.05). These facts suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting from the aggravation of preeclampsia. From the viewpoint of coagulation and fibrinolysis disorders, the predictive value in order to decide the optimal time for the termination of pregnancy could be recommended when the coagulation index exceeded 1.20.

Antithrombins↗

PubMed2000

[Inflammation of the myocardium as an arrhythmia trigger].

In patients with acute or chronic myocarditis, arrhythmias are a common and often the only clinical symptom in the natural course of the disease. The potentially malignant tachy- and bradyarrhythmias are of particular significance in the differential diagnosis of sudden cardiac death in myocarditis. Factors responsible for the increased incidence of cardiac arrhythmias are structural changes, parameters of ventricular dynamics and vascular changes. On the one hand, inflammatory processes in the cardiac myocytes and interstitium can lead directly to fluctuations in membrane potential. Fibrosis and scarring of the myocardial tissue and secondary hypertrophy and atrophy of the myocytes favor the development of ectopic pacemakers, late potentials and reentry as a result of inhomogeneous stimulus conduction. Furthermore, parameters of ventricular dynamics such as increased wall tension, increased myocardial oxygen consumption and diminished coronary reserve in the case of disturbed systolic or diastolic left ventricular function also contribute to the increased incidence of arrhythmias. Lastly, vascular factors can further increase the arrhythmogenicity of the inflamed myocardium through the disturbance of micro- and macrovascular perfusion and the resulting myocardial ischemia. Non-invasive rhythmological evaluation by 24 h Holter ECG, measurement of ventricular late potentials and heart rate variability can be used for orienting risk stratification of the at-risk patient with myocarditis. Programmed atrial and ventricular electrophysiological stimulation also has a relatively high predictive value for spontaneous ventricular tachyarrhythmias. It should be emphasized that, at the present time, optimal electrophysiological parameters with a high predictive value do not exist. In a selected patient population, immunosuppressive therapy in addition to conventional antiarrhythmic therapy can lead to the reduction or complete suppression of spontaneous and inducible arrhythmias. Nevertheless, in the interim, further precautionary antiarrhythmic measures such as serial antiarrhythmic treatment, VT ablation and ACID implantation are necessary in patients with malignant cardiac arrhythmias. Right ventricular myocardial biopsy for demonstration or exclusion of myocarditis is an important additional examination which can improve the differential diagnosis and treatment of patients with cardiac arrhythmias of unclear etiology.

Adult↗

PubMed2002

Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution.

Intradermal injection of naked DNA results in gene transfer to skin cells, but the efficiency of this gene transfer method is relatively low and variable. We have systematically optimized several parameters to obtain reproducible, high-level gene transfer to the mouse skin. Older mice (approximately 7 weeks) showed a significant decrease in gene expression compared with younger mice (4-5 weeks old). The composition of the solvent vehicle (electrolyte versus nonelectrolyte) strongly affected gene expression in the skin. A higher level of gene expression was achieved when naked DNA was dissolved in isotonic phosphate buffered saline solution compared with isotonic dextrose solution. Finally, transfection efficiency in older mice was greatly improved by increasing the ionic strength of the solvent vehicle. The improved transfection efficiency was due to an enhanced DNA uptake by the skin cells. Gene transfer was most evident in the subdermal smooth muscle cells and epidermal cells. With the optimized conditions, gene transfer mediated by intradermal injection of naked DNA was comparable in efficiency to electroporation. However, cellular distributions of the gene transfer of the two methods were different.

Animals↗

PubMed2006

Molecular depth profiling with cluster ion beams.

Peptide-doped trehalose thin films have been characterized by bombardment with energetic cluster ion beams of C60+ and Aux+ (x = 1, 2, 3). The aim of these studies is to acquire information about the molecular sputtering process of the peptide and trehalose by measurement of secondary ion mass spectra during erosion. This system is important since uniform thin films of approximately 300 nm thickness can be reproducibly prepared on a Si substrate, allowing detailed characterization of the resulting depth profile with different projectiles. The basic form of the molecular ion intensity as a function of ion dose is described by a simple analytical model. The model includes parameters such as the molecular sputtering yield, the damage cross section of the trehalose or the peptide, and the thickness of a surface layer altered by the projectile. The results show that favorable conditions for successful molecular depth profiling are achieved when the total sputtering yield is high and the altered layer thickness is low. Successful molecular depth profiles are achieved with all of the cluster projectiles, although the degree of chemical damage accumulation was slightly lower with C60. With C60 bombardment, the altered layer thickness of about 20 nm and the damage cross section of about 5 nm2 are physically consistent with predictions of molecular dynamics calculations available for similar chemical systems. In general, the model presented should provide guidance in optimizing experimental parameters for maximizing the information content of molecular depth profiling experiments with complex molecular thin film substrates.

Algorithms↗

PubMed1997

Clinical treatment planning optimization by Powell's method for gamma unit treatment system.

PURPOSE: This article presents a new optimization method for stereotactic radiosurgery treatment planning for gamma unit treatment system. METHODS AND MATERIALS: The gamma unit has been utilized in stereotactic radiosurgery for about 30 years, but the usual procedure for a physician-physicist team to design a treatment plan is a trial-and-error approach. Isodose curves are viewed on two-dimensional computed tomography (CT) or magnetic resonance (MR) image planes, which is not only time consuming but also seldom achieves the optimal treatment plan, especially when the isocenter weights are regarded. We developed a treatment-planning system on a computer workstation in which Powell's optimization method is realized. The optimization process starts with the initial parameters (the number of isocenters as well as corresponding 3D isocenters' coordinates, collimator sizes, and weight factors) roughly determined by the physician-physicist team. The objective function can be changed to consider protection of sensitive tissues. RESULTS: We use the plan parameters given by a well-trained physician-physicist team, or ones that the author give roughly as the initial parameters for the optimization procedure. Dosimetric results of optimization show a better high dose-volume conformation to the target volume compared to the doctor's plan. CONCLUSION: This method converges quickly and is not sensitive to the initial parameters. It achieves an excellent conformation of the estimated isodose curves with the contours of the target volume. If the initial parameters are varied, there will be a little difference in parameters' configuration, but the dosimetric results proved almost to be the same.

Algorithms↗

PubMed2000

Purging of human breast cancer cells from stem cell products with an adenovirus containing p53.

Tumor cell contamination of stem cell products can contribute to tumor relapse following high-dose chemotherapy and stem cell rescue. Numerous techniques have been used to remove the tumor cells from stem cell products with the objective of prolonging relapse-free survival. However, to date these techniques have been relatively ineffectual and/or toxic to hematopoietic stem and progenitor cells. The differential infectivity of adenovirus (Adv) vectors for breast cancer cells, compared with hematopoietic cells, has suggested that Adv-p53 might provide an effective purging strategy. To facilitate the use of Adv-p53 as a clinical strategy, we undertook studies to determine the parameters necessary for optimal stem cell product purging. The parameters studied were the particle number to nucleated cell ratio, the duration of coincubation, the incubation volume, and the presence or absence of hematopoietic progenitor cells. We have found that these parameters are interdependent and conclude that a 4-hour coincubation with an Adv-p53 particle to nucleated cell ratio of 2000:1 with 2 x 10(8) nucleated cells/mL is optimal for tumor cell purging. Furthermore, this appeared to be a safe procedure, with total loss of clonogenic growth of breast cancer cells as well as no significant effect on progenitor cell function as determined by granulocyte-macrophage colony-forming unit assays.

Adenoviridae↗

PubMed2005

Cortical thickness analysis examined through power analysis and a population simulation.

We have previously developed a procedure for measuring the thickness of cerebral cortex over the whole brain using 3-D MRI data and a fully automated surface-extraction (ASP) algorithm. This paper examines the precision of this algorithm, its optimal performance parameters, and the sensitivity of the method to subtle, focal changes in cortical thickness. The precision of cortical thickness measurements was studied using a simulated population study and single subject reproducibility metrics. Cortical thickness was shown to be a reliable method, reaching a sensitivity (probability of a true-positive) of 0.93. Six different cortical thickness metrics were compared. The simplest and most precise method measures the distance between corresponding vertices from the white matter to the gray matter surface. Given two groups of 25 subjects, a 0.6-mm (15%) change in thickness can be recovered after blurring with a 3-D Gaussian kernel (full-width half max = 30 mm). Smoothing across the 2-D surface manifold also improves precision; in this experiment, the optimal kernel size was 30 mm.

Algorithms↗

PubMed2026

Large-scale simulation of coverage and error rate tradeoffs for cancer detection in cell-free DNA whole-genome sequencing.

MOTIVATION: Cell-free DNA (cfDNA) whole-genome sequencing (WGS) is a promising approach for detecting cancer recurrence. It enables cancer detection by identifying all tumor-derived cfDNA (ctDNA) molecules carrying somatic single nucleotide variants (sSNVs). While ideally, a sequencing platform should be highly accurate for reliable ctDNA detection, in reality, all sequencing platforms introduce sequencing errors that generate false positives indistinguishable from true SNVs. Understanding how sequencing parameters influence ctDNA detection sensitivity at low tumor fractions (TFs) in cfDNA samples is essential for guiding sequencing strategies in clinical contexts. To model cfDNA sequencing for tumor detection, which contains asymmetric noise and multiple interacting parameters, analytical modeling is intractable, motivating large-scale parallelized simulation. RESULTS: We developed a simulation framework to generate in silico cfDNA data across 10 cancer types. In total, 480 million cfDNA samples were simulated from tumor WGS profiles. Overall, the lowest detectable TF differs substantially between cancer types under identical sequencing conditions due to variations in mutational load. For cancers with high mutational load, 3× coverage with low-error techniques reliably detects TFs below 0.1%. In contrast, cancers with low mutational load require at least six-fold higher coverage to achieve comparable detection thresholds. Increasing sequencing quality scores from Q30 to Q55 at 30× coverage further enhances sensitivity, enabling detection of TFs as low as 1 × 10-5. This study provides a comprehensive framework for optimizing sequencing parameters, offering valuable guidance for tailoring future technology development for specific cancer types and clinical applications. AVAILABILITY AND IMPLEMENTATION: The code is publicly available at https://github.com/UMCUGenetics/cfdetect/tree/main.

Whole Genome Sequencing↗

PubMedDate not supplied

Evaluation of retrospective multisector and half scan ECG-gated multidetector cardiac CT protocols with moving phantoms.

PURPOSE: We evaluated independently retrospective half scan and multisector mode manufacturer's protocols and compared them with modified acquisition protocols to determine optimal imaging parameters for cardiac scanning. MATERIALS AND METHODS: Data were acquired using two fabricated gated moving phantoms. In half scan mode, the manufacturer's recommended pitch values were compared with adjacent values at different motion rates. In multisector mode, the manufacturer's protocols were compared with ones with different gantry speeds and pitch values at the same motion rates. Weighted CT dose indexes (CTDI) were obtained for all protocols. Gated and reformatted reconstructed images of the moving phantoms were evaluated. RESULTS: In half scan mode, slightly better image quality was observed by lowering the pitch value, but with an increase of 6.3% of the weighted CTDI. Better results were obtained in multisector mode by lowering the pitch value up to 0.2, but with an increase of 14.3% of the weighted CTDI. Optimal images were obtained with the lowest temporal resolution. CONCLUSIONS: Gated moving phantom studies offer the advantage of testing acquisition protocols of complex motions and of helping to establish appropriate protocols.

Electrocardiography↗

PubMed2006

Improvement of statistical potentials and threading score functions using information maximization.

We show that statistical potentials and threading score functions, derived from finite data sets, are informatic functions, and that their performance depends on the manner in which data are classified and compressed. The choice of sequence and structural parameters affects estimates of the conditional probabilities P(C|S), the quantification of the effect of sequence S on conformation C, and determines the amount of information extracted from the data set, as measured by information gain. The mathematical link between information gain and mean conformational energy, established in this work using the local backbone potential as model, demonstrates that manipulation of descriptive parameters also alters the "energy" values assigned to native conformation and to decoy structures in the test pool, and consequently, the performance of such statistical potential functions in fold recognition exercises. We show that sequence and structural partitions that maximize information gain also minimize the mean energy of the ensemble of native conformations. Moreover, we establish an informatic basis for the placement of the native score within an energy spectrum given by the decoy pool in a threading exercise. We discover that, among all informatic quantities, information gain is the best predictor of threading success, even better than the standard Z-score. Consequently, the choices of sequence and structural descriptors, extent of compression, and levels of discretization that maximize information gain must also produce the best potential functions. Strategies to optimize these parameters with respect to information extraction are therefore relevant to building better statistical potentials. Last, we demonstrate that the backbone torsion potential, defined by the trimer sequence, can be an effective tool in greatly reducing the set of possible conformations from a vast decoy pool.

Amino Acid Sequence↗

PubMed2005

Cost-effective manufacture of an allogeneic GM-CSF-secreting breast tumor vaccine in an academic cGMP facility.

BACKGROUND: GM-CSF-secreting, allogeneic cell-based cancer vaccines have shown promise for the treatment of a variety of solid tumors. We have now applied this approach to breast cancer. The aim of these studies was to optimize expansion parameters, qualify the manufacturing process, and establish expected outcomes for cGMP-compliant manufacturing of two GM-CSF-secreting breast tumor cell lines. METHODS: The variables affecting the efficiency of expanding and formulating two allogeneic GM-CSF-secreting cell lines, 2T47D-V and 3SKBR3-7, were systematically evaluated. Production criteria investigated included alternative cell culture vessels (flasks vs. cell factories), centrifugation time and speed variables for large volume cell concentration, cell seeding density, the minimal concentration of FBS required for maximal cell expansion, and the dose and timing of irradiation in relation to cryopreservation. RESULTS: These studies demonstrate that, in comparison with standard 150-cm2 tissue culture flasks, Nunc 10-Stack Cell Factories are a more efficient and practical cell culture vessel for vaccine cell line manufacture. Centrifugation optimization studies using the COBE 2991 Cell Processor established that a speed of 2000 r.p.m. (450 g) for 2 min reliably concentrated the cells while maintaining acceptable viability and bioactivity. Radiation studies established that lethal irradiation prior to cryopreservation does not compromise the quality of the product, as measured by post-thaw cell viability and GM-CSF cell line-specific secretion levels. Finally, studies aimed at optimizing the production of one vaccine cell line, 3SKBR3-7, demonstrated that seeding the cells at a higher density and maintaining them in half the initial concentration of FBS maximized the yield of bioactive cells, resulting in significant cost savings. DISCUSSION: A manufacturing process that simultaneously maximizes cell yield, minimizes cell manipulation and maintains vaccine cell potency is critical for producing cell-based cancer vaccines in an academic setting. These studies define a feasible, reproducible and cost-effective methodology for production of a GM-CSF-secreting breast cancer vaccine that is cGMP compliant.

Academic Medical Centers↗

PubMed2005

Chemical and biological flocculation process to treat municipal sewage and analysis of biological function.

The pilot-scale experimental apparatus and the procedure of the chemical and biological flocculation process to verify the feasibility in treating Shanghai municipal sewage were introduced in this paper. In addition, the biological function of the process was discussed. The results of optimal running showed that in the reaction tank, the concentration of mixed liquor suspended solid(MLSS) was 2 g/L, hydraulic retention time(HRT) was 35 min, dosage of liquid polyaluminium chloride(PAC) was 60 mg/L, and the concentration of polyacrylamide(PAM) was 0.5 mg/L. The effluent average concentrations of COD(Cr), TP, SS and BOD5 were 50 mg/L, 0.62 mg/L, 18 mg/L, and 17 mg/L, respectively. These were better than the designed demand. In addition, the existence of biological degradation in this system was proven by several methods. The removal efficiencies of the chemical and biological flocculation process were 20% higher than that of the chemical flocculation process above at the same coagulant dosage. The treatment process under different situations was evaluated on a pilot-scale experiment, and the results provided magnificent parameters and optimal condition for future operation of the plant.

Acrylic Resins↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗

PubMed2000

Effect of initially limited resuscitation in a combined model of fluid-percussion brain injury and severe uncontrolled hemorrhagic shock.

OBJECT: Studies of isolated uncontrolled hemorrhage have indicated that initial limited resuscitation improves survival. Limited resuscitation has not been studied in combined traumatic brain injury and uncontrolled hemorrhage. In this study the authors evaluated the effects of limited resuscitation on outcome in combined fluid-percussion injury (FPI) and uncontrolled hemorrhage. METHODS: Twenty-four swine weighing 17 to 24 kg each underwent FPI (3 atm) and hemorrhage to a mean arterial pressure (MAP) of 30 mm Hg in the presence of a 4-mm aortic tear. Group I (nine animals) was initially resuscitated to a goal MAP of 60 mm Hg; Group II (nine animals) was resuscitated to a goal MAP of 80 mm Hg; and Group III (control; six animals) was not resuscitated. After 60 minutes, the aortic hemorrhage was controlled and the animals were resuscitated to baseline physiological parameters and observed for 150 minutes. Mortality rates were 11%, 50%, and 100% for Groups I, II, and III, respectively (Fisher's exact test; p = 0.002). The total hemorrhage volume was greater in Group II (69+/-32 ml/kg), as compared with Group I (41+/-18 ml/kg) and Group III (37+/-3 ml/kg) according to analysis of variance (p < 0.05). In surviving animals, cerebral perfusion pressure, cerebral blood flow (CBF), cerebral venous O2 saturation (ScvO2), and cerebral metabolic rate of O2 did not differ among groups. Although CBF was approximately 50% of baseline during the period of limited resuscitation in Group I, ScvO2 remained greater than 60%, and arteriovenous O2 differences remained within normal limits. CONCLUSIONS: In this model of FPI and uncontrolled hemorrhage, early aggressive resuscitation, which is currently recommended, resulted in increased hemorrhage and failure to optimize cerebrovascular parameters. In addition, a 60-minute period of moderate hypotension (MAP = 60 mm Hg) was well tolerated and did not compromise cerebrovascular hemodynamics, as evidenced by physiological parameters that remained within the limits of cerebral autoregulation.

Animals↗

PubMed2006

Optimizing UV laser focus profiles for improved MALDI performance.

Matrix assisted laser desorption/ionization (MALDI) applications, such as proteomics, genomics, clinical profiling and MALDI imaging, have created a growing demand for faster instrumentation. Since the commonly used nitrogen lasers have throughput and life span limitations, diode-pumped solid-state lasers are an alternative. Unfortunately this type of laser shows clear performance limitations in MALDI in terms of sensitivity, resolution and ease of use, for applications such as thin-layer sample preparations, acceptance of various matrices (e.g. DHB for glycopeptides) and MALDI imaging. While it is obvious that the MALDI process has some dependence on the characteristics of the laser used, it is unclear which features are the most critical in determining laser performance for MALDI. In this paper we show, for the first time, that a spatially structured laser beam profile in lieu of a Gaussian profile is of striking importance. This result enabled us to design diode-pumped Nd : YAG lasers that on various critical applications perform as well for MALDI as the nitrogen lasers and in some respects even better. The modulation of the beam profile appears to be a new parameter for optimizing the MALDI process. In addition, the results trigger new questions directing us to a better understanding of the MALDI process.

Algorithms↗