Immunosuppressive effects of streptozotocin-induced diabetes result in absolute lymphopenia and a relative increase of T regulatory cells.

OBJECTIVE Streptozotocin (STZ) is the most widely used diabetogenic agent in animal models of islet transplantation. However, the immunomodifying effects of STZ and the ensuing hyperglycemia on lymphocyte subsets, particularly on T regulatory cells (Tregs), remain poorly understood. RESEARCH DESIGN AND METHODS This study evaluated how STZ-induced diabetes affects adaptive immunity and the consequences thereof on allograft rejection in murine models of islet and skin transplantation. The respective toxicity of STZ and hyperglycemia on lymphocyte subsets was tested in vitro. The effect of hyperglycemia was assessed independently of STZ in vivo by the removal of transplanted syngeneic islets, using an insulin pump, and with rat insulin promoter diphtheria toxin receptor transgenic mice. RESULTS Early lymphopenia in both blood and spleen was demonstrated after STZ administration. Direct toxicity of STZ on lymphocytes, particularly on CD8(+) cells and B cells, was shown in vitro. Hyperglycemia also correlated with blood and spleen lymphopenia in vivo but was not lymphotoxic in vitro. Independently of hyperglycemia, STZ led to a relative increase of Tregs in vivo, with the latter retaining their suppressive capacity in vitro. The higher frequency of Tregs was associated with Treg proliferation in the blood, but not in the spleen, and higher blood levels of transforming growth factor-β. Finally, STZ administration delayed islet and skin allograft rejection compared with naive mice. CONCLUSIONS These data highlight the direct and indirect immunosuppressive effects of STZ and acute hyperglycemia, respectively. Thus, these results have important implications for the future development of tolerance-based protocols and their translation from the laboratory to the clinic.

Generic approach for the sensitive absolute quantification of large undigested peptides in plasma using a particular liquid chromatography-mass spectrometry setup.

A generic LC-MS approach for the absolute quantification of undigested peptides in plasma at mid-picomolar levels is described. Nine human peptides namely, brain natriuretic peptide (BNP), substance P (SubP), parathyroid hormone 1-34 (PTH), C-peptide, orexines A and B (Orex-A and -B), oxytocin (Oxy), gonadoliberin-1 (gonadothropin releasing-hormone or luteinizing hormone-releasing hormone, LHRH) and α-melanotropin (α-MSH) were targeted. Plasma samples were extracted via a 2-step procedure: protein precipitation using 1vol of acetonitrile followed by ultrafiltration of supernatants on membranes with a MW cut-off of 30 kDa. By applying a specific LC-MS setup, large volumes of filtrates (e.g., 2×750 μL) were injected and the peptides were trapped on a 1mm i.d.×10 mm length C8 column using a 10× on-line dilution. Then, the peptides were back-flushed and a second on-line dilution (2×) was applied during the transfer step. The refocalized peptides were resolved on a 0.3mm i.d. C18 analytical column. Extraction recovery, matrix effect and limits of detection were evaluated. Our comprehensive protocol demonstrates a simple and efficient sample preparation procedure followed by the analysis of peptides with limits of detection in the mid-picomolar range. This generic approach can be applied for the determination of most therapeutic peptides and possibly for endogenous peptides with latest state-of-the-art instruments.

Stochastic dominance and absolute risk aversion

In this paper we proose the infimum of the Arrow-Pratt index of absoluterisk aversion as a measure of global risk aversion of a utility function.We then show that, for any given arbitrary pair of distributions, thereexists a threshold level of global risk aversion such that all increasingconcave utility functions with at least as much global risk aversion wouldrank the two distributions in the same way. Furthermore, this thresholdlevel is sharp in the sense that, for any lower level of global riskaversion, we can find two utility functions in this class yielding oppositepreference relations for the two distributions.

Relative and absolute reliability of the clinical version of the Narrow Path Walking Test (NPWT) under single and dual task conditions.

Decline in gait stability has been associated with increased fall risk in older adults. Reliable and clinically feasible methods of gait instability assessment are needed. This study evaluated the relative and absolute reliability and concurrent validity of the testing procedure of the clinical version of the Narrow Path Walking Test (NPWT) under single task (ST) and dual task (DT) conditions. Thirty independent community-dwelling older adults (65-87 years) were tested twice. Participants were instructed to walk within the 6-m narrow path without stepping out. Trial time, number of steps, trial velocity, number of step errors, and number of cognitive task errors were determined. Intraclass correlation coefficients (ICCs) were calculated as indices of agreement, and a graphic approach called "mountain plot" was applied to help interpret the direction and magnitude of disagreements between testing procedures. Smallest detectable change and smallest real difference (SRD) were computed to determine clinically relevant improvement at group and individual levels, respectively. Concurrent validity was assessed using Performance Oriented Mobility Assessment Tool (POMA) and the Short Physical Performance Battery (SPPB). Test-retest agreement (ICC1,2) varied from 0.77 to 0.92 in ST and from 0.78 to 0.92 in DT conditions, with no apparent systematic differences between testing procedures demonstrated by the mountain plot graphs. Smallest detectable change and smallest real change were small for motor task performance and larger for cognitive errors. Significant correlations were observed for trial velocity and trial time with POMA and SPPB. The present results indicate that the NPWT testing procedure is highly reliable and reproducible.

Non-invasive quantification of brain glycogen absolute concentration.

The only currently available method to measure brain glycogen in vivo is 13C NMR spectroscopy. Incorporation of 13C-labeled glucose (Glc) is necessary to allow glycogen measurement, but might be affected by turnover changes. Our aim was to measure glycogen absolute concentration in the rat brain by eliminating label turnover as variable. The approach is based on establishing an increased, constant 13C isotopic enrichment (IE). 13C-Glc infusion is then performed at the IE of brain glycogen. As glycogen IE cannot be assessed in vivo, we validated that it can be inferred from that of N-acetyl-aspartate IE in vivo: After [1-13C]-Glc ingestion, glycogen IE was 2.2 +/- 0.1 fold that of N-acetyl-aspartate (n = 11, R(2) = 0.77). After subsequent Glc infusion, glycogen IE equaled brain Glc IE (n = 6, paired t-test, p = 0.37), implying isotopic steady-state achievement and complete turnover of the glycogen molecule. Glycogen concentration measured in vivo by 13C NMR (mean +/- SD: 5.8 +/- 0.7 micromol/g) was in excellent agreement with that in vitro (6.4 +/- 0.6 micromol/g, n = 5). When insulin was administered, the stability of glycogen concentration was analogous to previous biochemical measurements implying that glycogen turnover is activated by insulin. We conclude that the entire glycogen molecule is turned over and that insulin activates glycogen turnover.

Accurate memory for object location by individuals with intellectual disability: Absolute spatial tagging instead of configural processing?

Using head-mounted eye tracker material, we assessed spatial recognition abilities (e.g., reaction to object permutation, removal or replacement with a new object) in participants with intellectual disabilities. The "Intellectual Disabilities (ID)" group (n=40) obtained a score totalling a 93.7% success rate, whereas the "Normal Control" group (n=40) scored 55.6% and took longer to fix their attention on the displaced object. The participants with an intellectual disability thus had a more accurate perception of spatial changes than controls. Interestingly, the ID participants were more reactive to object displacement than to removal of the object. In the specific test of novelty detection, however, the scores were similar, the two groups approaching 100% detection. Analysis of the strategies expressed by the ID group revealed that they engaged in more systematic object checking and were more sensitive than the control group to changes in the structure of the environment. Indeed, during the familiarisation phase, the "ID" group explored the collection of objects more slowly, and fixed their gaze for a longer time upon a significantly lower number of fixation points during visual sweeping.

Measurement of absolute cell volume, osmotic membrane water permeability, and refractive index of transmembrane water and solute flux by digital holographic microscopy.

ABSTRACT. A dual-wavelength digital holographic microscope to measure absolute volume of living cells is proposed. The optical setup allows us to reconstruct two quantitative phase contrast images at two different wavelengths from a single hologram acquisition. When adding the absorbing dye fast green FCF as a dispersive agent to the extracellular medium, cellular thickness can be univocally determined in the full field of view. In addition to the absolute cell volume, the method can be applied to derive important biophysical parameters of living cells including osmotic membrane water permeability coefficient and the integral intracellular refractive index (RI). Further, the RI of transmembrane flux can be determined giving an indication about the nature of transported solutes. The proposed method is applied to cultured human embryonic kidney cells, Chinese hamster ovary cells, human red blood cells, mouse cortical astrocytes, and neurons.

Movement evaluation of overerupted upper molars with absolute anchorage: An in-vitro study

Introduction: The overeruption of upper molars due to the premature loss of antagonist teeth can be treated with the help of miniscrews. The aim of this study was to evaluate the movement of a typodont molar according to the biomechanical approach used with miniscrews. Study design: The study was conducted with four plaster models filled with typodont wax. In each model we used one absolute anchorage on the palatal side and another on the buccal side in different positions, thus generating four different biomechanical systems. A force of 150 g was applied to each side of the resin tooth. Periapical radiographs were taken preintrusion and immediately after completion of the intrusion. Photographs were taken in both the sagittal and occlusal planes every 3 min. The radiographic films and photographs were measured and compared. Results: A vertical movement of the molar was observed in all the models, with system 4 showing the greatest movement. Rotation in the occlusal plane only occurred in system 2, while in system 1 there was a change in the axial axis of 37 degrees. Conclusions: The anchorage site and the combination of forces applied may determine the resulting tooth movement

Dynamic analysis of belt-drives using the absolute nodal coordinate formulation

Belt-drive systems have been and still are the most commonly used power transmission form in various applications of different scale and use. The peculiar features of the dynamics of the belt-drives include highly nonlinear deformation,large rigid body motion, a dynamical contact through a dry friction interface between the belt and pulleys with sticking and slipping zones, cyclic tension of the belt during the operation and creeping of the belt against the pulleys. The life of the belt-drive is critically related on these features, and therefore, amodel which can be used to study the correlations between the initial values and the responses of the belt-drives is a valuable source of information for the development process of the belt-drives. Traditionally, the finite element models of the belt-drives consist of a large number of elements thatmay lead to computational inefficiency. In this research, the beneficial features of the absolute nodal coordinate formulation are utilized in the modeling of the belt-drives in order to fulfill the following requirements for the successful and efficient analysis of the belt-drive systems: the exact modeling of the rigid body inertia during an arbitrary rigid body motion, the consideration of theeffect of the shear deformation, the exact description of the highly nonlinear deformations and a simple and realistic description of the contact. The use of distributed contact forces and high order beam and plate elements based on the absolute nodal coordinate formulation are applied to the modeling of the belt-drives in two- and three-dimensional cases. According to the numerical results, a realistic behavior of the belt-drives can be obtained with a significantly smaller number of elements and degrees of freedom in comparison to the previously published finite element models of belt-drives. The results of theexamples demonstrate the functionality and suitability of the absolute nodal coordinate formulation for the computationally efficient and realistic modeling ofbelt-drives. This study also introduces an approach to avoid the problems related to the use of the continuum mechanics approach in the definition of elastic forces on the absolute nodal coordinate formulation. This approach is applied to a new computationally efficient two-dimensional shear deformable beam element based on the absolute nodal coordinate formulation. The proposed beam element uses a linear displacement field neglecting higher-order terms and a reduced number of nodal coordinates, which leads to fewer degrees of freedom in a finite element.

The Intonation of absolute questions of Brazilian Portuguese

In this paper we describe three melodic patterns of absolute interrogatives from a phonetic point of view, obtained from a corpus in Goiás (Brazil). The patterns are: a) Rising Final Inflection (30% to 52%), b) Rising-Falling Final Inflection, c) High Nucleus Final Inflection. These patterns have been established from the acoustic analysis and standardisation of 55 questions and from the verification of their validity in a perception test. We compared them with interrogative patterns obtained in different parts of Brazil and also in two Romance languages, Spanish and Catalan.

Development of beam and plate finite elements based on the absolute nodal coordinate formulation

The focus of this dissertation is to develop finite elements based on the absolute nodal coordinate formulation. The absolute nodal coordinate formulation is a nonlinear finite element formulation, which is introduced for special requirements in the field of flexible multibody dynamics. In this formulation, a special definition for the rotation of elements is employed to ensure the formulation will not suffer from singularities due to large rotations. The absolute nodal coordinate formulation can be used for analyzing the dynamics of beam, plate and shell type structures. The improvements of the formulation are mainly concentrated towards the description of transverse shear deformation. Additionally, the formulation is verified by using conventional iso-parametric solid finite element and geometrically exact beam theory. Previous claims about especially high eigenfrequencies are studied by introducing beam elements based on the absolute nodal coordinate formulation in the framework of the large rotation vector approach. Additionally, the same high eigenfrequency problem is studied by using constraints for transverse deformation. It was determined that the improvements for shear deformation in the transverse direction lead to clear improvements in computational efficiency. This was especially true when comparative stress must be defined, for example when using elasto-plastic material. Furthermore, the developed plate element can be used to avoid certain numerical problems, such as shear and curvature lockings. In addition, it was shown that when compared to conventional solid elements, or elements based on nonlinear beam theory, elements based on the absolute nodal coordinate formulation do not lead to an especially stiff system for the equations of motion.

Measurement of the absolute fluorescence quantum yield of rhodamine B solution using a dual-beam thermal lens technique

The dual-beam thermal lens technique has been found to be very effective for the measurement of fluorescence quantum yields of dye solutions. The concentration-dependence of the quantum yield of rhodamine B in methanol is studied here using this technique. The observed results are in line with the conclusion that the reduction in the quantum yield in the quenching region is essentially due to the non-radiative relaxation of the absorbed energy. The thermal lens has been found to become abberated above 40 mW of pump laser power. This low value for the upper limit of pump power is due to the fact that the medium is a resonantly absorbing one.

Solvent Effect on Absolute Fluorescence Quantum Yield of Rhodamine 6G Determined Using Transient Thermal Lens Technique

Dual beam thermal lens tecbnique is successfully employed for the determination of absolute Fluorescence quantum yield of rhodamine 6G lnser dye in different solvents. A 532 nm radiation from a Q-switched Nd:YAG laser was used for the excitation purpose. The fluorescence quantum yield values are found to be strongly influenced by environmental effects. It has been observed that fluorescence yield is greater for rhodamine 6G in ethylene glycol system than in water or in methanol. Our results also indicate that parameters like concentration of the dye solution, aggregate formation and excited state absorption affect the absolute values of fluorescence yield significantly.

Pulsed Photoacoustic Determination of Absolute Fluorescent Quantum Yield of the Laser Dye Rhodamine B

Pulsed photoacoustic technique which is found to be a very convenient and accurate method, is used for the determination of absolute fluorescence quantum yield of laser dye rhodamine B. Concentration and power dependence of quantum yield of rhodamine B in methanol for excitation at 532 nm is reported here. Results show that a rapid decrease in quantum yield as the concentration is increased and finally it reaches the limit corresponding to fluorescence quenching.