Relaxation Techniques

Relax Your Mind

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Effects of Exogenous VEGF on Development of Experimental Pulmonary Hypertension and Endotheliumdependent Relaxation

In addition to its well-known angiogenic properties, VEGF has been shown to protect against endothelial vascular injury and to improve endothelial function. Our previous finding of impaired endothelium-dependent relaxation in chronic hypoxic pulmonary hypertension 1 invited an investigation of whether lung VEGF overexpression can protect against hypoxic pulmonary hypertension and alter the development of pulmonary vascular remodeling.

Relaxation Mechanisms

So far the generation of the background field fluctuations has been assumed to derive solely from the field of a tumbling dipole, interacting with other dipole fields (the so-called 'dipole-dipole' interaction). However any process that generates such a random field can induce relaxation and some of the more important mechanisms will be discussed now (Harris, 1986 Gadian, 1982 Callaghan, 1991). For many spin 1 2 nuclei, this is the most important mechanism for inducing relaxation. This is particularly so for the common biological elements 1H, 13C, 23Na and 31P. The dipole-dipole interaction is heavily modulated by r, the internuclear separation, so that the longitudinal relaxation rate varies as r-6, thus so the interaction will become diminished if nuclei under consideration become significantly separated. Also note the strong dependence on y so that the dipole-dipole relaxation mechanism is much more effective for 1H than for the previously mentioned nuclei. The magnetic moment of...

Nuclearspin Relaxation

Magnetic nuclei in a magnetic field can adopt nuclear-spin states of different energy. As a system reaches equilibrium, the population differences between the different nuclear-spin states decays exponentially through relaxation. The intensity of a resonance signal in the NMR spectrum is related to the difference in population between the two energy levels of the different nuclear-spin states. This means that the rate at which this difference returns to equilibrium and relaxation has a profound effect on the sensitivity and resolution of an NMR spectrum. Longitudinal magnetisation, Mz, is restored to its equilibrium value Mzo by longitudinal relaxation, characterised by the longitudinal relaxation time T1. Transverse magnetisation, Mx and My, decays by transverse relaxation characterised by the transverse relaxation time T2. Nuclear-spin relaxation is mainly modulated via through-space interactions between different nuclear spins and via Brownian rotational tumbling as the orientation...

Changes In Muscle Contractionrelaxation

This type of response may be caused by several mechanisms. For instance, the muscle relaxation induced by succinylcholine, discussed in more detail in Chapter 7, is due to blockade of neuromuscular transmission. Alternatively, acetylcholine antagonists such as tubocurarine may compete for the receptor site at the skeletal muscle end plate, leading to paralysis of the skeletal muscle. Botulinum toxin binds to nerve terminals and prevents the release of acetylcholine the muscle behaves as if denervated and there is paralysis.


The absorption of energy by the system makes it unstable, and it immediately starts to move, or relax, back to a state of equilibrium. The absorbed energy is dispersed by a number of processes, known collectively as relaxation mechanisms. These mechanisms can be grouped into those that transfer energy away from the spins to 'the lattice',1 and those that redistribute it within the spin system (Figure 6.7) (Goldman, 1988 Harris, 1986 Gadian, 1982 Abragam, 1961 Slichter, 1963 Callaghan, 1991 Belton, 1994). The former processes contribute to transverse relaxation (T2) and also spin lattice, or T1 relaxation (see Chapter 5). The latter mechanisms contribute exclusively to the decay of the transverse component of the bulk magnetization M, acting to make the individual isochromats lose phase coherence. As a result, the net component of magnetization lying in the transverse plane dephases, and the detectable signal diminishes (Figure 6.8). Of particular note is the rate at which the signal...

Fundamentals Of Nmr Spectroscopy

In theory, any measurable NMR spectroscopic parameter may be used to investigate binding of a ligand to a protein, but in practice they are limited to measurements that can be determined easily and with a sufficient degree of sensitivity. There are two main approaches used in drug discovery today. The first approach examines chemical shift changes of the protein upon binding of a ligand and the second examines the NMR signals of the ligand and their change upon binding to a protein. In addition, there are also two complementary approaches that examine changes in relaxation or diffusion behaviour of a ligand upon binding to a protein 34, 35 .

Ligandbased Screening

The transverse relaxation time, T2, of small molecules is usually long compared to that of proteins and therefore the resonance signals for small molecules are generally much narrower than those of proteins. However, upon binding of a ligand to a protein, T2 of the ligand will more closely resemble that of the protein, resulting in line broadening of the ligand-associated signals. Line broadening in the NMR spectrum of a ligand following addition of a macromolecule to the sample is a clear indication of binding. Furthermore, the extent of line broadening, and therefore the sensitivity of the experiment, is related to the size of the protein - with larger structures usually having a more pronounced effect on T2 of the ligand. The longitudinal relaxation time, T1, of small molecules is also altered by binding to proteins, resulting in the observation of negative NOEs for bound ligand resonances 41 . Ligand binding can therefore be detected by measuring a 2D 1H-1H -NOESY spectrum of the...

Nmr Backbone Assignment Of A Kinase

PKA is not currently a drug target due to its broad spectrum activity and multiple physiological functions. However, it is considered to be a useful protein for studying other protein kinases 53 . Several X-ray structures of PKA, with and without bound inhibitors, have been published. The structure of the non-phosphorylated, inactive structure was, however, unknown. The authors were keen to emphasise the dynamic nature of proteins, particularly the conformational changes occurring upon activation, and upon binding of substrates and inhibitors, and point out that NMR is an ideal tool for studying motional processes by relaxation analysis. Selective labelling of PKA with 15N-labelled Phe, Tyr, Leu, Asp, Ile and Val was carried out allowing more facile assignment of the peaks due to those residues. For example, it was possible to assign 19 out of the 20 resonances due to valine in the protein using this approach. 13C-labelled Tyr was used in conjunction with 15N-labelled Val allowing the...

Stimulated nitric oxide synthase activity in vitro

The blood flow to the skin is greatly enhanced in human pregnancy and investigation of the cutaneous circulation provides insight into pregnancy-induced mechanisms of vasodilatation. Small subcutaneous arteries (250-300 mm) obtained from subcutaneous fat at Cesarean section relaxed in response to the endothelium-dependent vasodilator ACh to the same extent as similar arteries from non-pregnant women (McCarthy et al., 1994). Interestingly, the NO synthase inhibitor, l-NMMA, failed to completely inhibit relaxation to ACh, and indomethacin had little effect. The residual relaxation to ACh in the presence of the NOS inhibitor was greater in the arteries from pregnant women and suggests the presence of an additional endothelium-derived hyperpolarizing factor (Gerber et al., 1998). Pre-constricted small subcutaneous arteries from normotensive pregnant women have enhanced relaxation to another endothelial vasodilator bradykinin (BK), compared with non-pregnant women (Knock and Poston, 1996)....

Endotheliumderived hyperpolarizing factor

A number of studies have suggested that prostaglandin and NO-independent but endothelium-dependent mechanisms of relaxation are enhanced in human pregnancy (McCarthy et al., 1994 Pascoal and Umans, 1996). Acetylcholine-induced vasodilatation that persists despite inhibition of cyclo-oxygenase and NO synthase is greater in pregnant compared with virgin rats. In both groups, elevation of the potassium concentration in the organ bath totally abolished any remaining relaxation, which is strongly indicative of a role for enhanced synthesis of EDHF.

Stimulated NO synthesis in vitro

There are many aspects of endothelial dysfunction that culminate in the development of pre-eclampsia, the abnormal relaxation to agonists representing just one endothelial cell defect. In small subcutaneous arteries, sensitivity to both ACh (McCarthy et al., 1994) and to BK is reduced in women with pre-eclampsia compared with normo-tensive pregnant women (Knock and Poston, 1996). Using omental vessels from women with preeclampsia, Pascoal et al. (1998) found relaxation to ACh was totally absent whilst responses to BK were unaffected when compared to normotensive controls. Studies using small myometrial arteries from pre-eclamptic women showed that relaxation to BK was completely absent, whereas normoten-sive controls relaxed well (Ashworth et al., 1997). Other studies using similar vessels showed that maximal responses to ACh were reduced in pre-eclamptic women (Kublickiene et al., 1998). Whilst these studies generally agree that endothelium-dependent dilatation is impaired in women...

Circulating angiogenic factors in preeclampsia

Regulatory role in the process of trophoblastic invasion. Reduced endothelium-dependent relaxation of blood vessels incubated in pre-eclamptic serum in the presence of anti-VEGF antibody suggests a role for low concentrations of VEGF in the pathogenesis of pre-eclampsia (Brockelsby et al., 1999).

Compressibility and Thermal Expansion

Although the values of protein thermal expansion coefficients appear to be reasonable in relation to those of comparable polymers and small molecules of similar nature, protein compressibilities are much smaller than would be expected if proteins are impermeable to solvent 75 . Because of their hardness, knots can be expected to have low compressibilities, but the considerable empty space in matrices and surfaces should produce high values if the interior of proteins were mechanically isolated from the environment through which the pressure is applied. Thus far it is found that the hemoglobins have isothermal or adiabatic compressibilities in the normal range for liquids, but most other proteins studied had values characteristic of soft solids. Apparent compressibilities would be consistent with 100 knot and no free volume. The explanation appears to be that although the true low knot compressibilities contribute correctly to the apparent compressibilities, the matrices are permeable...

Sources for Further Study

Nezu. Social Problem-Solving in Adults. In Advances in Cognitive-Behavioral Research and Therapy, edited by Philip C. Kendall. Vol. 1. New York Academic Press, 1982. An excellent summary of problem-solving therapy. As indicated by its title, the Kendall book in which this article appears also contains other informative articles dealing with cognitive behavior therapy. Goldfried, Marvin R. The Use of Relaxation and Cognitive Relabeling as Coping Skills. In Behavioral Self-Management Strategies, Techniques, and Outcomes, edited by Richard B. Stuart. New York Brunner Mazel, 1977. A description of systematic rational restructuring by Marvin Goldfried, who developed the technique reveals its similarities to and differences from rational-emotive therapy. Maultsby, Maxie C., Jr. Rational Behavior Therapy. Englewood Cliffs, N.J. Prentice-Hall, 1984. An excellent summary of rational behavior therapy, as developed by Maultsby discusses self-talk and its...

Platelet Vegf Contents In Patients With Pulmonary Hypertension Or With Chronic Hypoxemic Lung Disease

VEGF released from platelets and acting specifically on endothelial cells may play a pivotal role. In systemic vessels, increasing VEGF bioavailability at sites of endothelial denudation has been shown to accelerate endothelial repair and to limit neointima formation 34 . Moreover, VEGF overexpression within the vascular wall has been shown to restore endothelium-dependent relaxation and to protect against vasoconstriction and platelet activation. The overall balance between VEGF and other platelet-derived non-specific mitogens such as PDGF may, therefore, be of importance in pulmonary vascular diseases and pulmonary hypertension.

Piezoelectric Devices

Design criteria for detectors intended to be applied for dosimetry and measurement of material properties will generally differ from those intended for diagnostic use, particularly in relaxation of an extreme requirement for sensitivity in diagnostic application there is always an underlying requirement to maximise the information derived from a given exposure to a patient. Thus, for narrow-band and multiple spot-frequency measurements on materials and solutions, quartz is a good detector in spite of its relatively low coupling coefficient, whilst for measurements directed at 'exposimetry' (see Section 3.8), where small physical size and uniform frequency response are generally important, it is convenient to use miniature ceramic or PVDF detectors ('hydrophones') in essentally non-resonant conditions.

Docking Methodologies

A new method called relaxed complex methods has been described by Lin et al. (2002). It allows an induced fit of the targeted protein. First, several target conformations should be generated as above. In a second phase, a simple, coarse-grained scoring algorithm is used to allow fast docking of a small set of molecules. The last step corresponds to a more accurate positioning and evaluation of the free energies of binding of the best complexes. The program Slide also enables the motion and relaxation of binding-site side chains in response to the presence of a docked ligand (the so-called induced fit) (Schnecke and Kuhn 2000).

Psychosocial Treatments

Some consumers object to taking medications because of concern about the long-term use of psychotropic medication, or because they are opposed to the ingestion of chemical substances for philosophical or religious reasons. Such individuals may explore alternative treatments. Nutritional supplements and special dietary regimens have been used since the 1950s, but thus far there is no solid scientific support for this approach (Torrey, 2001). Others try homeopathic remedies, or relaxation techniques. Patricia Deegan, a consumer advocate, has written a manual on nonmedical strategies for reducing and coping with symptoms called Coping with Voices Self Help Strategies for People Who Hear Voices That Are Distressing (1995). For example, when experiencing aversive auditory hallucinations, some consumers may obtain relief by listening to soothing music with headphones. (For more information on Dr. Deegan, see the biography in Chapter 12.) The exploration and use of alternative treatments for...

Benefits of Meditation

Research on the physiological effects of meditation led to the application of meditative techniques as a treatment to combat stress-related illnesses. Meditators have often experienced significant decreases in such problems as general anxiety, high blood pressure, alcoholism, drug addiction, insomnia, and other stress-related problems. Researchers have also found that the scores of meditators on various psychological tests have indicated general mental health, self-esteem, and social openness. Many psychologists argue, however, that these effects are not unique to meditation and can be produced by means of other relaxation techniques. Meditation researcher Robert Ornstein has suggested that the long-term practice of meditation may induce a relative shift in hemispheric dominance in the brain from the left hemisphere, which is associated with such linear processes as language and logical reasoning, to the right hemisphere, which is associated with nonlinear processes such as music...

Homogeneous Liquidlike Media

Absorption of the wave energy results in its degradation to heat. This occurs when the density fluctuations in the medium get out of phase with the sound pressure fluctuations. In 'homogeneous' media (e.g. solutions of macromolecules) the mechanisms by which this is known to occur are relaxation mechanisms. These are not fully understood even in very simple media but arise from the time-lag that is inherent in the perturbation of any physical or chemical equilibrium initiated by the cyclic fluctuations of the wave parameters. At any instant in time the total wave energy may be viewed as being shared amongst a number of different forms of energy translational energy, molecular vibrational and structural energy, and lattice vibrational and structural states. As time varies, redistribution of the energy occurs, but at finite rates determined by the precise coupling processes relevant to the propagation medium. The coupling processes themselves constitute the absorption mechanisms, the...

Inhomogeneous Media Including Gas Bubbles

When the propagation medium is not a homogeneous fluid, mechanisms other than the structural or thermal relaxation of its molecular constituents may contribute to the excess absorption (Morfey 1968). In addition to scattering the sound waves (covered in Chapter 6), inhomogeneities in the inertial or elastic properties of the medium can be responsible for the extraction of the acoustic wave energy by either viscous or thermal processes.4 Viscous damping results from the relative motion that occurs, between a suspended structure and the embedding medium, when the density of the inhomogeneity is different from that of the medium. If the density of the inhomogeneity is uniform, it will simply attempt to move back and forth along the axis of sound propagation. If the density is not uniform, there will also be a tendency for relative rotational motion to occur. In either case absorption of acoustic wave energy occurs when the velocity amplitude of the relative motion is diminished because...

Hydrationinduced Conformational Changes

Ments in spectral resolution on hydration are confined to the peak at 40 ppm. This begins at a hydration of about 0.2 h 62 . The source of this behavior is not understood, but could reflect reordering of disulfide bridges, a decrease in the linewidth of contributing resonances from lysine side chains due to increased motional averaging on hydration, or titration shifts induced by hydration. The latter two explanations, however, seem unlikely. Proton-carbon cross-relaxation times do not change very significantly on hydration, while titration shifts would be expected to occur at much lower hydrations than is observed as water adds to ioniz-able side chains and normalizes their pKa values. With the exception of the changes in the peak at 40 ppm, hydration appears to have little effect on the solid state spectrum, and so the distribution of conformations sampled by fully hydrated BSA is as broad as that observed in the dry protein. The most interesting result of these studies, however, is...

Free fatty acids oxidative stress and vascular dysfunction

Increased serum FFA, as a facet of the metabolic syndrome, adversely alters vascular function and constitutes an independent risk factor for coronary disease (Sattar et al., 1998). Experiments on endothelial cells in culture and on rat femoral artery segments in vitro suggest that physiologically relevant concentrations of FFA cause reductions in vasodilator prostacyclin and nitric oxide and reductions in vascular relaxation responsiveness (Davda et al., 1995 Endresen et al., 1994). In lean, insulin-sensitive subjects, manipulations to increase circulating FFA levels to the range observed in insulin-resistant patients (two- to ninefold elevations) impair relaxation to the endothelium-dependent vasodilator methacholine as measured by leg blood flow (Steinberg et al., 1997, 2000). Endogenous FFA correlate well with adverse vascular function in vivo (Steinberg et al., 1996, 1997, 2000). As discussed by these authors, elevated FFA may induce formation of reactive oxygen species which...

Administration of TSHSuppressive Doses of LThyroxine

There is no doubt that subclinical hyperthy-roidism increases the risk of atrial fibrillation 35 . Careful investigations, however, have also shown subtle cardiac dysfunction in these patients as evident from an increased left ventricular mass, impaired ventricular relaxation, and reduced exercise performance 36 . The long-term consequences of this cardiac dysfunction are unknown, but b-blockade improves cardiac function 36,37 . If there is a clear indication for marked TSH suppression, it may be prudent to prescribe b-blockers. This may be especially worthwhile if the patient does not tolerate the high doses of thyroxine.

Biologically Relevant Simple Media

Hueter (1958) appears to have been the first to point out that a positive relationship exists between the attenuation coefficient and the structural 'complexity' of biological media. The 'simple' media referred to above are water and biological molecules in aqueous solution or suspension. Because of a suspected predominant involvement of molecular relaxation mechanisms in determining ultrasonic attenuation in tissues, the ultrasonic study of aqueous solutions of macromolecules has been quite intensive. Pauly and Schwan (1971), in particular, have convincingly demonstrated, by attenuation measurements on liver and on a homogenate of subcellular components of liver, that most of the attenuation is due to absorption at the macromolecular level. Further discussion of molecular mechanisms is taken up in Chapter 7. Some of the properties of water were discussed in Section 4.3.5, where mention was made of the two-state model for structural relaxation by water molecules, proposed by Hall...

Foldingunfolding rates mvalues

Protein folding and unfolding rates can be studied by using stopped-flow measurements. Upon rapid mixing of unfolded protein in water (i.e. by diluting the concentration of the denaturant that was used to unfold the protein this can be done within 2-5 ms), one can observe the formation of native structure, i.e. folding, by spectroscopic methods, for example changes in fluorescence or CD (circular dichroism) signal. The typical result is to observe an exponential relaxation towards the new equilibrium state the characteristic time constant gives the folding time. One can generalize this approach to measure how the protein folds in the presence of different concentrations of denaturant then one can study how the folding rate kf(D) depends on denaturant concentration D . Similarly, one can start from the folded state and study how the unfolding rate ku(D) depends on denaturant concentration.

Basic airway opening techniques

Basic airway opening manoeuvres are simple techniques that can be performed anywhere and without the use of equipment. In most situations, the commonly used techniques of head tilt chin lift and or jaw thrust will be all that is required to relieve airway obstruction caused by the relaxation of soft tissues. These very basic manoeuvres have been described as part of basic life support (BLS) in Chapter 5.

Changes in Acceptor Stem Identity Elements Correlate with Changes in the Code

Additionally, animal mitochondria have experienced a dramatic reduction in their genome size and, in particular, in the number of tRNA genes 89 . If, as we propose, an initial requirement for changes in the code is the relaxation of the recognition constraints between ARS and tRNAs, then the large amount of variations in the genetic code of animal mitochondria should correlate with a large amount of changes in the 'operational RNA code' imbedded in their acceptor stem sequences.

Algebraic Reconstruction Algorithms

Algebraic reconstruction techniques are based on relaxation methods for solving systems of linear equalities or inequalities. Recent developments suggest that with proper tuning, the convergence of these algorithms can be very fast. However, the quality of the reconstructions has not been investigated thoroughly. In this section, a summary overview of algebraic reconstruction techniques is first set out, followed by a description of the algorithmic implementation of the classical algebraic reconstruction technique (ART) and its variants. The ART algorithm is based on the Kaczmarz method and uses a successive over-relaxation method well-known in numerical linear algebra.4 It was first proposed as a reconstruction method in 1970 by Bender et al.5 and was applied mainly to X-ray photography and electron microscopy. The early developments addressed mainly reconstruction of X-ray CT data but more recently, ART-type algorithms have been proposed specifically for PET.6 The principle of the...

Dielectric Theory And Measurements

These molecules are oriented by a torque proportional to the product of the field strength and the dipole moment of each molecule, and this is hindered by frictional forces whose extent depends on the angular frequency w of the (sinusoidal) field and the characteristic relaxation time t of the molecule. At low frequencies (mt 1), the orienting torque overcomes the frictional forces, and the material exhibits a high relative permittivity es, sometimes called the static permittivity. The electrical capacitance C of the material, when held between two plane-parallel electrodes of area A separated by a distance d, is thus defined at low frequencies (on neglecting fringe fields) by

First category effects

S-nitrosated oxy-hemoglobin is vasodilating without release of free NO (cf Fig. 7). The sensitivity of aortic tissue to GSNO is very high, and of the same order of magnitude as the sensitivity to the physiological stimulant acetyl choline (Ach) (Fig. 8). The vasodilation of aortic rings is considerably reduced when superoxide levels in the organ bath are arti -cially raised by coincubation with pyrogallol 89 , a generator of superoxide radicals. Seen as NO donors various RSNOs can produce both bene cial and adverse effects on cells and tissues. This state of affairs reminds us of the ongoing controversy surrounding the bene-ts disadvantages of upregulation of NOS enzymes. Many detailed studies in vitro and in vivo suggest that raising levels of free NO be bene cial in vascular ischemia, but harmful in brain ischemia. Accordingly, many therapeutic treatments of ischemia involve NO donors for vas-culature, and NOS inhibitors for brain. Experiments con rm many similarities between the...

Cramer Rao Minimum Variance Bound

Phantoms can be made from a single component or mixtures. Geometric objects, used for size or volume standards, are often made of acrylic. Major manufacturers are Perspex in the UK and Plexiglas in North America. These are immersed in water (doped to reduce its T1 and T2 values). Objects with a specified T1, T2 or diffusion value can be made from a container filled with liquid or gel, often with various salts added to reduce the relaxation times. Chemical compounds are available from suppliers such as Sigma-Aldrich. Phantoms should ideally be stable with known properties. Water has the advantage of being easily available, and of a standard composition. Its intrinsic Ti & 3.3 s, T2 & 2.5 s at room temperature (see Table 3.6 below), and in its pure form these long relaxation times usually cause problems. The long Ti can lead to incomplete relaxation with sequences that may allow full relaxation with normal brain tissue (Ti & 600 ms for normal white matter at 1.5T see Chapter 5, Figure...

Concluding Remarks

The general model that has emerged from the dielectric studies is that globular proteins in solution attract to themselves from one to two layers of bound water, which represents from 0.3 to 0.7 g of protein-associated water per g dry protein. The extent of association of this water to the protein molecule is such that it can be thought of as a shell that contributes to the protein's effective radius of rotation, as depicted in Fig. 2. A small proportion of this hydration is either internal water that forms an integral part of the protein structure 73 or else is so strongly bound to the protein that the water molecules have orientational relaxation times equal to or longer than that of the protein molecule. Most of the hydration shell, however, consists of water that is not so strongly bound as to inhibit rotational freedom as much as this. A quite detailed picture is available for myoglobin, where it has been shown 7,30 that half of the hydration shell exhibits orientational...

Databanks and Databases

For NMR, the principal databases for storage of NMR experimental data and solved structures are the BioMagResBank, and the Protein Data Bank (PDB) curated by the Research Collaboratory for Structural Bioinformatics (RCSB). The BMRB stores all non-coordinate biomolecular NMR data (Doreleijers et al. 2003) chemical shifts, NOEs, coupling constants, residual dipolar couplings (RDCs), hydrogen exchange rates and protection factors, order parameters, atomic relaxation parameters, and molecular correlation times. The PDB is the central repository for all coordinates and also manages restraint files used for NMR structure calculation (Berman et al. 2000). Most journals require structures and NMR data to be published in PDB and BMRB.

Hirschsprungs disease 109

Rectal manometry Shows absence of internal sphincter relaxation with a reduction in intraluminal pressure in the anal canal following distension of the rectum with a balloon (rarely performed except in older children). Rectal biopsy For definitive diagnosis, mucosal submucosal suction biopsies without need for anaesthesia or full-thickness biopsy under anaesthesia.

Why It May Be Impossible to Reconstruct Hereditary Relations between Proteins Based Solely on Their Sequence Similarity

Firstly, the correlation function C(t), which measures the probability of an amino acid not to be affected by mutations in time X, decays exponentially, so that beyond the correlation function relaxation time one can not relate the sequences original, and the one observed at time X later. Secondly, it did not make a difference if we started our design procedure from one sequence or from two unrelated sequences. These sequences diverged so much from each other in a short design simulation time, that one could not identify which initial sequence we used in the design procedure. Furthermore, our results29 suggested that some degree of homology may occur even between sequences that converged from unrelated root to the same structure, i.e., in clear analogs. The reason for that is that as we showed in reference 29 some positions may feature conserved residues due to physical requirement of stability of a common fold. Physical conservation of certain classes of amino acids at some positions...

Mice Lacking Either the PKGI or Pkgii Have Distinctive Phenotypes

Mice lacking either PKGI or PKGII have also been studied recently. PKGI-null mice have notable alterations in smooth muscle function. Motor activity in the gastrointestinal tract is highly disorganized and transit of foodstuffs through the gut is profoundly slowed. PKGI has been found in both the smooth muscle of the gastrointestinal tract as well as in some of the neurons of the enteric neural ganglia, and the absence of the PKGI from both of these tissues is likely to contribute to the dysfunction of gastrointestinal motility. Likewise, modulation of vascular smooth muscle function in these mice is impaired, consistent with the established importance of PKGI in promoting vasodilation. As a result, male PKGI-null mice have low ability to reproduce because of impaired relaxation of the smooth muscle in the vasculature of the penis, and the PKGI-null mice are somewhat hyper

Role of Neurotransmitters

Certain neurotransmitters serve in the inhibition of neuronal activity. The most common of these is gamma-aminobutyric acid (GABA), found primarily in the diencephalon region of the brain. Here GABA acts to reduce the activity within the region. Antianxiety drugs such as valium or lib-rium appear to work by enhancing the activity of GABA, resulting in the relaxation of skeletal muscles. Antidepression compounds such as Prozac and Zoloft appear to function through blockage of serotonin uptake by neurons.

Subcellular Targeting Defines Protein Phosphatase Functions

Another phosphatase targeting mechanism was identified in smooth muscle. Preparations of smooth muscle myosin contain a tightly associated protein phosphatase that dephosphorylated myosin light chain and promoted smooth muscle relaxation. The myosin-bound phosphatase was shown to be a complex of three polypeptides, PP1 catalytic subunit, a 130-kDa myosin binding subunit (also known as MBS) and a 20-kDa regulatory subunit. The 130-kDa polypeptide is capable of binding both PP1 and myosin. The 20-

Some Practical Applications

While this study induced a phobic reaction in the subject, systematic de-sensitization is a procedure designed to eliminate phobias and anxieties. The procedure was largely developed and named by South African-born therapist Joseph Wolpe. Noting that it is very difficult to have pleasant and anxious feelings simultaneously, Wolpe fashioned a systematic technique to teach clients to engage in behavior (relaxation) that competes with anxiety. The client and therapist now move on to the next phase of therapy. While remaining fully relaxed, the client is asked to imagine being in the first situation at the bottom of the list. The image is held for several seconds. The client then relaxes for about twenty seconds before imagining the same situation again for several seconds. When the client is able to imagine an item and remain fully relaxed, the therapist presents a slightly more fearful situation to imagine. This procedure continues until an image causes distress, at which time the...

Jwm Bulteand Lh Bryant Jr

Certain chemical structures have magnetic properties that enable faster proton relaxation, allowing their use as MR contrast agents or magnetopharmaceuticals when found biocompatible. Larger complexes such as macromolecular or particulate contrast agents have recently emerged as a distinct subgroup of magnetic materials, suitable for contrast enhancement of the blood pool and specific tissues. This chapter describes the latest advances in chemical engineering and molecular cellular biology, which are producing an entirely new class of (targeted) MR contrast agents that can be used for high-resolution imaging of biologic processes at the molecular and cellular level. Image contrast in MR imaging is largely determined by the magnetic relaxation times of tissues. Following a radiofrequency (RF) pulse at the resonance frequency (42.57 MHz Tesla), protons absorb the electromagnetic radiation, and return or relax to the lowest energy state of alignment with the applied magnetic field. This...

Too Many Young Volunteer Studies

Many volunteer studies, especially at commercial, academic and university clinical units, are frequently young people of college age. Both males and females will volunteer since financial remuneration, and a free medical check-up and medical care play their part in motivation. The young also have less career and family commitments interfering with their motivation. Time for studying, reading and relaxation within an atmosphere of camaraderie also contributes to the availability of younger volunteers, who, because of their age, also tend to be very healthy. It will readily be appreciated that most drugs or devices are not unique or life saving but hopefully an improvement on existing agents, and indeed this applies to most basic research experiments. Nearly all drug studies in Phase I are aimed at gathering data on a potentially safe and possibly efficacious dose range. As a

Intracellular Polyamines Underlie Physiological Inward Rectification

Match the relaxation time constants of inward rectifiers observed in intact cells, providing further evidence that polyamine block causes inward rectification in vivo (4,5). In contrast to the classical strong inward rectifiers, weakly rectifying channels, such as Kirl.1 (ROMK1) and KATp channels, all exhibit very weak affinity for spermine and other polyamines, and a much shallower voltage dependence of polyamine block. Polyamines have also been demonstrated to cause inward rectification in AMPA kainate receptors and cyclic nucleotide-gated channels, although block of these channels is not as potent as the block of Kir channels (15,16).

Biological Basis Of T

In normal tissues Ti values are related to macro-molecule concentration, water binding and water content. This is the reason for the basic Ti contrast in the brain myelin causes white matter to have a shorter T1 than grey matter (Figure 5.2). The absolute T1 of each tissue will depend on field strength (Figure 5.3). T1 can be changed in pathology. For instance, oedema around tumours or in inflammatory acute MS lesions leads to an increase in T1. T1 is also increased in chronic MS lesions, probably as a result of the reduction in myelin and increase in water content. Conversely, T1 is reduced at the rim of active MS lesions by the presence of cellular debris which constitute extra-relaxation centres in the fluid. Bottomley's review (Bottomley etal., 1987) remains the most extensive review of T1 (and T2) values in normal and pathological tissues across a range of field strengths.

Gait Analysis Observation and Manual Evaluation

The individual needs strength in the muscles of the ankle, knee, hip, and trunk to stand up and walk without external support. Correct timing of the contraction and relaxation in these muscle groups is required for practical balance and gait (Horak and Nashner 1986 Eberhart et al. 1954). Exercises on the mats and treatment table are used to help bring the muscles to the level of strength needed for function.

Psychopharmacological Prevention of PTSD

Part of effective treatment of PTSD involves prevention of full-blown PTSD from developing by intervening as immediately posttrauma as one can with debriefing, crisis intervention, and psychological first aid. This is particularly true in cases of Acute Stress Disorder. Interventions that can reduce immediate and acute posttrauma levels of arousal, such as relaxation training and utilizing social supports, are often effective. Can pharmacological treatment play a role in prevention or early intervention Stahl (2005) suggests that medications can be given to disrupt the psychobiological processes that lead to PTSD, ideally preventing the disorder but conservatively attenuating its severity. Two studies suggest that administration of propranolol may be effective as its effects on suppressing epinephrine may interfere with the formation of strong traumatic memories. Still other research is suggesting that early use of benzodiazepines and SSRIs, too, may be helpful. More research needs to...

Cardiovascular Function

Cardiac output at rest is not substantially changed with age in the absence of superimposed cardiac disease. However, components of the cardiac cycle are indeed changed. Heart rate is decreased, reflecting the decrease in parasympathetic withdrawal noted previously, and perhaps impaired b-adrenergic and sinoatrial function. Left ventricular mass and left ventricular stroke volume are increased, which allows cardiac output to be maintained in the face of decreased heart rate. However, diastolic relaxation is slowed, making the late left ventricular filling that is associated with atrial contraction a more important determinant of stroke volume in the elderly. Chronotropic response to b-adrenergic stimulation is impaired, but it is uncertain if this is the cause or the result of increased circulating norepinephrine levels (44). Cellular and molecular mechanisms for these changes have been studied in some detail in animal models and may offer some insight into drug responses. The...

Therapeutic Relationships

Psychotherapists have recognized that many patients have difficulty with changing their patterns of living because of anxiety or lack of skill and experience in behaving differently. Behavioral therapy techniques are especially useful in such cases. In cases of anxiety, the patient can be taught to relax through relaxation training exercises. The patient gradually imagines performing new, difficult behaviors while relaxing. Eventually, the patient learns to stay relaxed while performing these behaviors with the psychotherapist and other people. This process is called desensitization, and it was originally developed to treat persons with extreme fears of particular objects or situations, termed phobias. New behavior is sometimes taught through modeling techniques in which examples of the behavior are first demonstrated by others. Behavioral psychotherapists have also shown the importance of rewarding small approximations to the new behavior that is the goal. This shaping technique...

How is an MR image produced

The hydrogen nuclei act like tiny spinning bar magnets (magnetic moments) and within the MRI scanner they align themselves parallel or anti-parallel to the external magnetic field. If radiowaves RF of a critical frequency (the resonant or Lamor frequency) are generated, some of the nuclei absorb energy causing them to change their orientation relative to the external magnetic field. This causes rotation of the net magnetisation vector to rotate through a certain angle - flip angle, e.g. 90 degrees. The greater the strength and duration of the RF pulse, the greater the flip angle. At the same time, all of the nuclei begin to spin in phase with one another. When the RF is turned off, the nuclei start to relax towards their resting state. The magnetisation vector returns to its original orientation (T1 relaxation). Immediately following the RF pulse, the individual magnetic moments are rotating in phase. Simultaneously with T1 relaxation, there is dephasing of the spins (T2 relaxation)....

How is tissue contrast created

A long train of radiowave pulses make up the imaging sequence. The duration and timing of the pulses determine which tissue properties will be reflected in the final image, e.g. the T1 or T2 relaxation rates (T1- or T2-weighted image). Images may also be weighted for the proton density of tissues, which corresponds to their free-water content. Therefore, unlike CT, tissue contrast in MRI is variable, and an understanding of the sequence used is required in order to interpret images.

Hypertensive cardiomyopathy

When studied with echocardiography, many normal pregnant women show a degree of ''physiologic'' diastolic dysfunction. Schannwell etal. (2001) demonstrated affected LV relaxation with a reduction in peak early diastolic flow and an increase of isovolu-metric relaxation time at 33 weeks gestation in normal pregnant women. In pregnant patients with mild chronic hypertension they showed definite signs of diastolic dysfunction with delayed relaxation noted as early as the beginning of the gestation. Some patients with pregnancy-associated hypertension developed diastolic dysfunction at midgestation, while others only showed this abnormality at term. They concluded that in healthy pregnant women, the increased preload associated with normal pregnancy results in a reversible physiologic left ventricular hypertrophy, a significant alteration in diastolic left ventricular function (disturbed relaxation pattern) and a temporary decrease in the efficacy of...

Beta receptor agonists

When an asthmatic attack has been triggered by histamine at H1 receptors, the objective is to redilate the bronchi with a E2 receptor agonist in the upper and mid airways. These cause relaxation of bronchial smooth muscle and thus allows the airway to dilate. These materials are mainstays of the treatment of asthma, as well as a variety of other pulmonary diseases in which it is desired to decrease airway resistance. They provide rapid symptomatic relief where the predominant cause of reduced airway calibre is bronchial smooth muscle contraction, or they may be used as regular maintenance therapy to avert symptoms. Their preventative effect is particularly seen in the suppression of exercise-induced asthma41. Beta receptor agonists also increase the rate of mucociliary clearance, known to be abnormally slow in patients with obstructive airways disease. Inhaled E2 receptor agonists are less effective if airway inflammation is a major factor in the disease. The oldest member of the...

Study of Sleep Deprivation

If it were possible to allow animals to rest and relax but not sleep, would the sleep deprivation still prove fatal This question was addressed by anecdotal accounts of human sleep deprivation during the Korean War. As a means of extracting confessions from American soldiers, Korean military intelligence operatives commonly subjected prisoners of war to sustained bouts of sleep deprivation. In the face of overwhelming exhaustion and clear signs of personality disintegration, American soldiers were often induced to sign confessions of their alleged war crimes. However, Randy Gardner, a seventeen-year-old high school student, experienced sleep deprivation for 264 hours to get his name in the Guinness Book of World Records with no apparent permanent effects and no profound temporary deficits. Why would people respond in such radically different ways to sleep deprivation One hypothesis proposes that severe adverse effects arise as a function of stress and inability to rest and relax,...

Clinical Applications

Nocturnal enuresis, or bed-wetting, is a stage four developmental disorder present in about four million to five million children annually in the United States. The exact cause of this disorder is undetermined, although the extreme muscular relaxation during stage four sleep likely contributes to its occurrence. To prevent nocturnal enuresis, the patient must learn to

Etiology of erectile dysfunction after radical retropubic prostatectomy

Intraoperative damage to the neurovascular bundles, which initiate erections, is the main cause of erectile dysfunction after prostatectomy.1 These neurovascular bundles, comprised of cavernous nerves, release nitric oxide in response to sexual stimuli, which initiates a molecular cascade resulting in increased levels of cyclic guanosine monophosphate (cGMP). This cGMP potentiates corporal vasodilatation and smooth muscle relaxation, which ultimately produces an erection.9 Erectile dysfunction occurs immediately after radical prostatectomy secondary to disruption of the neurovascular bundles, and the return of sexual function may take up to 18 months in some individuals.1,20 This varied length of time of return of sexual function may be due to patient age. Younger patients are more likely to have excessive erectile capacity and greater neurovascular regenerative capabilities.21

Treatment Of Preterm Labour

Present on the myometrium and on activation can stimulate relaxation of the muscle. The effectiveness, however, is limited to extending pregnancy by approximately 48 h and there are significant maternal side effects such as tremor, tachycardia, arrhythmias and, in very rare cases, death. A delay in delivery of 48 h is useful as it allows the administration of steroids to the mother, which accelerates lung development of the foetus. In addition to ritodrine, other b-2 agonists have been used off-label in both the US and Europe, the most commonly prescribed being terbutaline. During recent years, the use of b-2 agonists has declined following cautions on the side effects and ritodrine has now been withdrawn in the US.

Plant Science Initiative N305 Beadle Center for Genetics Research University of Nebraska Lincoln NE 685880660 USA

As in the case of most animal systems, organellar genomes generally show strict maternal inheritance in plants. However, there are exceptions to this pattern. In some cases, paternal inheritance is observed, though varying degrees of biparental inheritance are also seen (Reboud and Zeyl, 1994 Zhang et al., 2003). In nearly all such exceptions, the plastid has been more likely to show variation from strict maternal inheritance than the mitochondrion. Why the relaxation of strict maternal inheritance pat

Motor Vehicle Accidents

Miller (1998) outlines three areas for treatment (1) reducing arousal, (2) cognitive-behavioral therapy, and (3) exposure therapy. Deep muscle relaxation, systematic desensitization, and cure-controlled breathing are common and useful techniques. Among the cognitive-behavioral modalities, Albert Ellis's rational-emotive therapy is considered specifically useful for accident survivors (Best & Ribbe, 1995) because of its focus on cognitions of fairness, causality, and control. Other more specific CBT techniques, including cognitive restructuring, thought stopping, and role playing, are also suggested. Finally, exposure therapy using in vivo exposure procedures have been found to be especially helpful for MVA-PTSD. If patients are particularly fixed on fears of injury, imaginal flooding may be used to augment in vivo procedures. Kuch (1989) suggests that when the victim is particularly avoidant of driving, exposure techniques as a passenger may have to be done first. Kuch also recommends...

Beyond the Reptation Model 41 The Motion of Kinks

Referring to Fig. 1A, a chain is shown inside a gel and is initially oriented horizontally. The picture shows the simulation results for a chain length of9000, using a method that will be discussed in Section 5. In Fig. IB, the field is applied downward, causing the chain to move in this direction. Because of the presence of the gel, its motion downward is severely impeded. The best the chain can do is to form vertically oriented kinks. However, whether or not it will do this depends on three different factors. Kinks are stretched and doubled back on themselves, and consequently, have less entropy than the chain inside the original tube, so entropy tends to disfavor kink formation. This entropy reduction is linearly proportional to the length of the kink. Another effect hindering kink formation is an elasdc curvature energy needed to bend the dp of the kink. Since the pore size in agarose is close to the persistence length of DNA, this effect is not too important. The final factor is...

Urinary stress incontinence 199

P Raised intra-abdominal pressure is not adequately transmitted to the proximal urethra, resulting in a disproportionate rise of bladder pressure over urethral pressure. Also, the descent of the urethra-vesical junction (from weakness in the pelvic floor muscles) results in a loss of normal sphincter closure. This is exacerbated during pregnancy, as progesterone promotes relaxation of the bladder and proximal urethral muscles.

Two Clinical Vignettes

Of the first device, conscious and unconscious anxiety from the past and present inhibits the conscious relaxation of the urethral sphincter bringing attention to bear on a conscious memory of feeling cock of the walk overrides the anxiety and allows the conscious relaxation of the sphincter.

Biological Reactivity Of Nitrates And Bioactivation

Mediation of the vasodilator response to GTN by NO requires the efficiency of bioactivation to NO to be high, since GTN induces tissue relaxation with nanomolar potency and bioactive concentrations of NO are also nanomolar 119-121 . However, inspection of the chemical reactions of nitrates, depicted in Fig. 5, indicates that there is no direct pathway for the 3e-reduction to NO. On the basis of chemical reactivity, the most facile reactions of nitrates in vivo are predicted to be

The Theory of Gait Training

Gait Training Hemiplegia Patient

The PNF techniques are useful when working with the patient in gait. Rhythmic Initiation, Replication, and Combination of Isotonics help the patient to learn a new motion or to move to a position. Use of Stabilizing Reversals and Rhythmic Stabilization to facilitates stability. Using Dynamic Reversals will reduce fatigue and promote coordination. Use Relaxation techniques to improve functional mobility.

Rape and Sexual Assault

Foa and Rothbaum (1998) suggest the use of general CBT techniques, including imaginal exposure, in vivo exposure, breathing retraining, cognitive restructuring, thought stopping, guided self-dialogue, deep muscle differential relaxation, and covert modeling and role playing. They mention some important treatment considerations for rape trauma victims that are critical to address. They begin by warning that rape victims are particularly and extremely avoidant, and if this issue is left unaddressed, it may significantly interfere with treatment. Suggestions for dealing with these high levels of avoidance include validation of the client's feelings, perhaps allowing for more cancellations and support clients when they do avoid treatment as a way to get them to come in for treatment. A supportive attitude and understanding is critical. Another complicating factor is that unlike with Panic Disorder and many other phobias, the fears and anxieties that a rape victim often feels are strongly...

Horowitzs Cognitive Analytic Approach

The next phase of treatment involves helping the patient improve his or her future coping style. These words are italicized because this treatment approach addresses the patients functioning in response to both current and anticipated stressors on the part of the patient-realistic or otherwise. It is explained that thoughts about the event or events are being inhibited and can be experienced in a dose-by-dose approach with specific controls rather than global inhibitions (Horowitz, 2001, p. 193) being utilized to cope. As defensive functioning is reduced, negative emotions will emerge but within the context of tolerable limits. If these experiences are too overwhelming, Horowitz (2001) suggests adding desen-sitization procedures for relaxation and self-control. Maladaptive defenses should give way to more consciously controlled and adaptive controls. Defensive operations such as inhibition of thought, suppression of emotion, distortion of reality,

Glass Transitions In Proteins

Expansivity Glass

The idea that water acts as a plasticizer of the protein conformation is not new it was suggested many years ago by Bone and Pethig 102 on the basis of dielectric relaxation studies (see Chapter 4). In recent years, several studies of fully hydrated proteins and protein crystals also have indicated the existence of a glasslike dynamical transition at about 200 K in proteins. It is well known that glass transition temperatures for synthetic polymers decrease with increases in plasticizer content, yet the possibility that the transition at 200 K in fully hydrated proteins and the transition observed at 298 K at low hydrations are related has been established only recently. In this section, we describe the 200 K transition as well as work on the hydration dependence of the transition temperature. We begin by briefly describing some basic properties of glass transitions in synthetic polymers. Further details can be found in Refs. 103-105 or other standard texts on synthetic polymers....

Effect Of Hydration On Protein Dynamics

A variety of techniques have been employed to examine the effect of hydration on the dynamic properties of the protein and of water at the protein surface. The results of studies employing dielectric relaxation and Rayleigh scattering of Moss-bauer radiation (RSMR) are described in other chapters of this book. Rupley and Careri 3 have recently provided an extensive review of the literature in this field. In many cases, the critical hydration levels found with time-averaged properties are also observed in the recovery of protein dynamic properties. In this section, we review some of these results. Protein-water interactions have been extensively investigated by NMR techniques using both hydrated powders and protein solutions. For reviews, see Kuntz and Kauzmann 1 , Bryant 71,72 , and Rupley and Careri 3 . Much of the work has been concerned with the relaxation properties of water at the protein surface using H, 2H, and 170 nuclei, but several solid state 13C NMR studies of hydrated...

Ar Coactivators And Prostate Cancer Development And Progression

Type I coactivators are bridging proteins between the DNA-bound nuclear receptor and the basal transcriptional machinery. Protein inhibitors of activated signal transducers and activators of transcription (STAT) factors (PIAS), whose members exert differential effects on AR activity, belong to this group. AR activation is stimulated by PIAS 1 and 3 but repressed by PIASy (87). P-catenin has a role in cell-cell adhesion by linking the cytoskeleton to adherens junctions, acting as a type I coactivator (88). As an effector of the wingless type MMTV integration site family (Wnt) pathway, P-catenin regulates proliferation, differentiation, and migration (89). Cytoplasmic P-catenin can form a complex with members of the T-cell factor and lymphoid enhancer factor family of transcription factors in the nucleus. Class II coactivators have histone acetyltransferase activity that is required for relaxation of chromatin structure. They stabilize ligand binding and influence translocation of the...

Vascular Supply And Innervation Of The Corpora Cavernosa

Penile autonomic innervation is responsible for regulating the tone of the cavernous smooth musculature and the intra-cavernous arteriolar smooth muscle. Relaxation of these muscles results in tumescence. While the penis is in the flaccid state, blood flow is limited by the basal tone of these smooth muscles. This tonic contraction is mediated by sympathetic stimulus from the cavernous nerves. The sympathetic pathway originates from the T10 to L2 spinal segments and travels through the sympathetic chain ganglia to the hypogastric plexus via the splanchnic nerves. The hypogastric plexus divides into two hypogastric nerves at the level of the aortic bifurcation. These two nerves enter the pelvis medial to the internal iliac vessels and deep to the endopelvic fascia. Both the hypogastric nerves and the pelvic continuation of the sympathetic trunks send branches to the pelvic plexus. In humans, the sympathetic fibers that contribute to the cavernosal nerves and regulate erection originate...

Viscoelasticity Semisolid Media

Maxwell Element

A molecular picture of viscoelasticity may, for example, be gained by considering a liquid between two plates one fixed and one oscillating to provide a sinusoidal shear stress. At low frequencies of oscillation all the driving energy is dissipated in viscous flow of the different layers of liquid over each other. Such flow occurs as a small directional drift superimposed on the random, thermal, molecular motion. If the frequency of the oscillating stress is increased until it is too fast for any molecular diffusion to occur during the period of shear strain, then the liquid will appear to possess shear rigidity no energy is dissipated in viscous flow, instead it is stored elastically. The change from viscous to elastic behaviour with increasing frequency, intermediate between these extremes, is called the 'viscoelastic relaxation'. In this case the viscoelastic relaxation time is the diffusional jump-time of the liquid molecules. With an alternating compression of low frequency the...

The Story of Paul Continued from Chapter

Ruth helped Paul set up a schedule that included study time, relaxation time, and meetings with her for support and problem solving. Paul's parents were skeptical about his plan to return to school. They were convinced that the stress of school is what had pushed him over the edge. However, with Ruth's help, Paul was able to tell them how important school was for him and how important their support would be to his success. Paul's parents agreed to support his plan as long as they could figure out what to do if Paul got sick again. Paul, his parents, and Ruth made a list of things that would indicate that he was experiencing another episode of his illness and the things people could do to help.

Viscoelastic Properties

Connective Tissue Hysteresis

Considering the complex hierarchical organization of tendons and ligaments, surrounding proteins, and ground substance, it is not surprising that they demonstrate nonlinear viscoelastic properties that are both time- and history-dependent. This essentially means that the elongation of the tissue is based not only on the amount of force but on the time and history of force application. A Medline search reveals published literature as early as 1969 on the viscoelastic properties of collagenous tissues (71,72). Time-dependent behavior of connective tissues has classically been examined using creep (21,71,73-84), stress relaxation, or hysteresis experimental methods. Creep is fundamentally simple to measure, where a constant load is applied to a tissue and the progressive time-dependent elongation is measured. The elongation amount should be measured with reference to markers on the sample rather than the separation of the grips to ensure no slippage occurs. Stress relaxation is measured...

Uterine Overdistension

The effect of uterine stretch on myometrial expression of G proteins (e.g., GsD), which mediate myometrial relaxation, is not known. Human studies of uterine overdistension are lacking. One recent study found no difference between singleton and multiple gestations in the levels of expression of GsD, PGE2 receptors, CX-43, and CX-26 in myometrium taken from nonlabor-ing women undergoing elective cesarean delivery at term (Lyall et al., 2002). Moreover, mechanical stretch did not alter the levels of GsD expression in vitro, and GsD expression was unaffected by steroid hormones. These findings suggest that the mechanisms by which uterine stretch can promote myometrial contractions in humans are complex and may involve additional factors or that multiple gestations that do not result in preterm labor may have compensatory mechanisms for the increased uterine stretch by preventing aberrant CAP expression.

Functional Autonomy and Personal Dispositions

Always evolving, Allport believed that the motivations of adulthood are often independent of the motivations of childhood, and he referred to this concept as functional autonomy. For example, a person who plays a musical instrument during childhood years because of parental pressure may play the same instrument for relaxation or enjoyment as an adult. Although not all motives are functionally autonomous, many adult activities represent a break from childhood and are based on varied and self-sustaining motives.

Cognitive Behavioral Therapies for PTSD

Relaxation training Joseph Wolpe developed systematic desensitization as a means to desensitize an individual to stimuli that is initially very arousing. It is a practice- or learning-based technique in which a desirable behavior that is incompatible with the undesired behavior is first established (Blake & Sonnenberg, 1998). Then, while engaged in the incompatible and positive behavior, typically a state of calm or relaxation, the patient is exposed to arousing or fear-inducing stimuli while attempting to remain calm and relaxed. Eventually, arousal in reaction to previously arousing stimuli will subside and be replaced by a relaxed state. A patient can then encounter arousing stimuli without the arousal reaction. Systematic desensitization is sometimes done with imagery exposure, making it more cognitive, but it is often used with real life stimuli, thus putting it in the behavioral camp. An anxiety hierarchy is developed in which a patient establishes how specific stimuli rank in...

The baby box Myth and reality

Systematic de sensitization Operant-conditioning techniques are also at work in helping those with significant fears and anxiety learn to live more effectively. A process called systematic desensitization is used to overcome the fear or anxiety associated with a particular stimulus. The premise behind systematic desensitization is that if a fear is learned or conditioned, it can then be unlearned by the process of extinction or by not reinforcing the behavior. The person undergoing this treatment is asked to either imagine the anxiety-producing situation or confront the real-life situation incrementally, while positive reinforcement is provided to help establish the perception of control over the stimulus. Occasionally, relaxation training accompanies the use of systematic desensitization whenever the anxiety-producing stimuli are present. It helps to increase the likelihood of a relaxed response to the feared stimulus. This behavior-modification treatment has been very successful at...

The Artificial Cell Membrane

Constants of the relaxation processes that are prevailing. This might involve the mass transport in an ion channel, the charging of the double layer capacitance in the electrolyte electrode interface or the diffusion of an electroactive ion to the electrode surface. Two different methods are available to interpret the impedance spectra, both of them rely on a proper identification of exactly what is going on. In the first case a physical model is evaluated and the corresponding flux equations are solved 44 . Thereafter, the impedance data are fitted to the resulting equation. In the other case an equivalent circuit is proposed, most often consisting of resistances and capacitances in series and or in parallel, reflecting the different suggested processes. Provided, the assumptions are correct, data fitting in both cases gives information on the electrochemical events in the interface. However, if the wrong equivalent circuit is chosen, data fitting yields numbers of little or no...

Experimental Biomechanical Testing

The classic sigmoid-shaped curve of tendons and ligaments have been emphasized over the years to demonstrate the unique arrangements of these tissues. The initial nonlinear or toe region, followed by the linear region, where stiffness is usually reported, and the failure region have been the foundation of many studies. Beyond a static or quasi-static tensile test of tendons and ligaments, other testing methods have been reported. These include low-load properties (57) biaxial tensile testing, viscoelastic properties creep (21) and stress relaxation (85), hysteresis (64), free vibration, forced oscillation and thermoelastic tests. Professor Woo and his group introduced the technique of a universal force sensor and robotics (44-46,48-50,53,58) to evaluate the mechanical properties of ligaments under more realistic physiological loading. Clearly, the evolu

Beyond Biased Reptation

Biased Reptation

The orientation seems to continuously increase as TV1 beyond the size at which a saturation is predicted by the theory. There is also a strong transient overshoot of the orientation at the onset of the field, and a fast relaxation process just after field interruption, which cannot be accounted for by the sole orientation of the tube in the field (other more subtle undershoots were reported, but we let them aside here to focus on the most spectacular observations). These effects were attributed to internal modes of the chains, i.e., to the failure of the assumption of constant tube length. The comparison of the main relaxation times of the orientation with mobility measurements on a molecular scale (107,108) and with field inversion results (109) support the idea that the antiresonance of the mobilty observed in FIGE and the orientation transient overshoot have a common molecular origin.

Internal Dynamics and NMR Structure Determination

MD simulations on peptides are of great interest, since one can perform fully solvated simulations in the hundreds of nanoseconds range, and the peptides may show very complicated dynamics, including reversible folding (Daura et al. 1999 Peter et al. 2001). In these cases, the interpretation of NMR relaxation data is particularly difficult, and the use of standard methods for structure determination is bound to fail. However, the direct back calculation of the complete spectra is possible from long MD simulations, therefore, there is no need to separate internal and rotational dynamics. The NMR parameters predicted from the simulation can be directly compared to the experiments. In terms of structure refinement, this is somewhat unsatisfactory, since one has to rely entirely on the accuracy of the MD simulations in atomic detail, and the experimental data do not enter directly. Simulations of sufficient length are still impossible for larger biological macromolecules. Inferring...

Examples of systems biology research1

3bpga Structure

APC-catalyzed degradation of cyclin-B and signals the exit of the M-phase and reentry into interphase. In addition, two net positive feedbacks play a role via Myt1-Wee1 and cdc25. It was shown experimentally 103 that in the absence of the degradation of cyclin-B by APC the resulting network is bistable. In the presence of cyclin-B degradation, the network displays the oscillations characteristic for the cell cycle more specifically, it functioned as a relaxation oscillator. Using a semi-detailed model (based on 18, 103 ), the authors modeled the network in the absence and the presence of the degradation of cyclin-B and found bistability and oscillations, respectively. Then they investigated the effects of the two net positive feedbacks by inhibiting them. This caused the core oscillator to engage in damped oscillations rather than prolonged oscillations indicating the essentiality of the positive feedback for proper functioning of the cell cycle. The model they used was only...

Viscoelastic Behavior

Viscous Elastic Modulus Hpam

There are three different methods to study viscoelastic materials stress relaxation test, creep test, and dynamic test. 2.5.1 Stress Relaxation Test If food materials are deformed to a fixed strain and the strain is held constant, the stress required to maintain this strain decreases with time. This is called stress relaxation. In this test, stress is measured as a function of time as the material is subjected to a constant strain. This test can be conducted in shear, uniaxial tension, or uniaxial compression. Figure 2.16 shows stress relaxation curves for elastic, viscous, and viscoelastic materials. As can be seen in Fig. 2.16, ideal viscous substances relax instantaneously but no relaxation is observed in ideal elastic materials. Viscoelastic materials relax gradually and stop depending on the Figure 2.16 Stress relaxation curves for elastic, viscous and viscoelastic materials From Steffe, J.F. (1996). Rheological Methods in Food Process Engineering, 2nd ed. East Lansing, MI...

Tissue Engineering Strategies For Acl Regeneration

Several studies have determined actual stresses and or strains generated in the ACL during knee loading in animals (36) or humans (37,38). The loads generated during normal usage are well below the failure load of the ACL and vary within the antero-medial and posterolateral bundle as a function of loading conditions. The mechanical properties of isolated femur-ACL-tibia complexes have also been studied under subfailure and failure conditions. The structural properties (breaking load, stiffness, and extensibility) and material properties (ultimate strength, modulus, and ultimate strain) of various tendons and ligaments have been determined from uniaxial constant strain rate failure testing (39,40). The ACL is anisotropic, nonlinear, and viscoelastic (experiences creep and stress relaxation), making it even more difficult to match its properties. To obtain design criteria, these mechanical properties must be prioritized, according to the most important to restore normal knee function...

Hypnosis and Meditation

Two popular nonchemical techniques for altering consciousness are hypnosis and meditation. Hypnosis was first discovered in the eighteenth century by Franz Mesmer, and its use has been marked by controversy ever since. An altered state is induced in hypnosis by the suggestive instructions of the hypnotist, usually involving progressive relaxation. The hypnotized subject often appears to be asleep but remains alert inside, exhibiting varying degrees of responsiveness to the suggestions of the hypnotist. Only about 10 percent of the population can enter the deepest hypnotic state, while another 10 percent cannot be hypnotized at all. The rest of the population can achieve some degree of hypnotic induction. Psychologists argue about whether hypnosis is a genuine altered state or simply a form of role playing. changes that occur during meditation. Some of the findings include a decrease in oxygen consumption of 16 percent during meditation (compared with an 8 percent drop during the...

PET Scanning in Oncology

Tomographie Injection

Asked to fast because it is both inappropriate and unnecessary to disrupt their blood glucose levels. All other patients are asked to fast for at least six hours prior to their scan but are again encouraged to drink plenty of water. On arrival in the department, the patient's personal details should be checked and a clear explanation of what the scan involves should be given. It is important to give the patient the opportunity to ask questions at this stage so as to ensure that they are completely relaxed. For this reason, the appointment time should include a pre-injection period of about 15 minutes. For 18F -FDG PET scanning it is advantageous to have the patient lying down for both the injection and the uptake period as this will hopefully aid relaxation and reduce unwanted muscle and brown fat uptake. In order to get the best out of the 18F -FDG PET scan it is important that certain key areas are given due consideration. The site of the body chosen for injection of the 18F -FDG is...

Blood Pressure

In the usual context, blood pressure refers to brachial artery pressure, which in the average adult is about 120 80. The 120 (in mm Hg) refers to systolic pressure, the brachial arterial pressure during cardiac ventricular contraction. The 80 is diastolic pressure, the brachial arterial pressure during cardiac ventricular relaxation. The average between the two, thus, is about 100. Such an average of 100 may be abnormal if the pulse difference (termed the arterial pulse pressure) is wide. For instance

Applications of the Principles of Behaviorism

The behaviorism of Watson has resulted in applications in psychology and many other disciplines. The most notable form of application of Watson's behaviorism is the psychological treatment known as systematic desensitiza-tion. This treatment was created by South African psychiatrist Joseph Wolpe (1915-1997). Systematic desensitization was designed to reverse the outcome of the classical conditioning process in which extremely intense negative emotional responses, such as fear or anxiety, are elicited by everyday aspects of the environment. This outcome is referred to as a phobia. The treatment first requires training in relaxation. The second component of treatment takes a person through a hierarchy of steps beginning with a setting very distant from the feared stimulus and ending with the problem setting. At each step, the individual is asked to note and in some manner signal the experiencing of fear or anxiety and then is instructed to relax. Movement through the hierarchy is...

Stress and dermatology

As far back as the 19th century, Hillier (1865), in working with eczema, implicated mental excitement, nervous debility and anxiety as the cause of these skin diseases. In 1982, Teshima and colleagues found that emotional stress had the capacity to influence the immune system to a great extent and that this would often manifest in cutaneous illness. They found that the tension in patients could lead to an enhancement of allergic reactions and these allergic patients were shown to improve with relaxation and autogenic training. There were also speculative implications for skin disease with the finding that the function of T-cells and the phagocytosis of macrophages were suppressed by induced stress. Furthermore, evidence of the strong relationship between the skin and the central nervous system (CNS) has been demonstrated by Ortonne and colleagues (1983) who noted that innervation of the CNS often produced blushing, perspiration and pallor.

Mechanisms Of Parturition Parturition

Placental CRH synthesis is stimulated by glucocorticoids, in contrast to the inhibitory effect of glucocorticoids on hypothalamic CRH synthesis. Placental CRH, in turn, promotes fetal cortisol and DHEA-S production, and this positive-feedback loop is progressively amplified, thereby driving the process forward from fetal HPA activation to parturition. Placental CRH, in turn, enhances prostaglandin production by increasing the levels of expression of prostaglandin H2 synthase (PGHS) chorion and amnion cells, creating yet another positive-feedback loop that drives the process of parturition. Paradoxically, during uterine quiescence CRH may act as a myometrial relaxant rather than as a promoter of parturition. Throughout most of pregnancy, the myometrium expresses CRH type 1 receptors that are linked by Gsa regulatory proteins to adenylate cyclase and cAMP, which would promote myometrial relaxation when they are stimulated. At the end of pregnancy, however, an alternative splice variant...

AT1 receptor autoantibodies

Brockelsby, J., Hayman, R., Ahmed, A., Warren, A., Johnson, I. and Baker, P. (1999). VEGF via VEGF receptor-1 (Flt-1) mimics preeclamptic plasma in inhibiting uterine blood vessel relaxation in pregnancy implications in the pathogenesis of preeclampsia. Lab. Invest., 79, 1101-11.

Nitrates As Nitric Oxide Mimetics

That responded to nitrosation of diaminorhodamine in the presence of NO 50,51 . In contrast, intracellular NO was detected using this fluorescent probe from a variety of agents that elevate NO acetylcholine (that activates endothelial NOS eNOS), and three separate NO donors (from different chemical classes). These agents were used at comparable concentrations to GTN and produced concentration-dependent responses. In addition, all four agents inhibited mitochondrial O2 consumption, an effect associated with the interaction between NO and cytochrome c oxidase, and of potential pathophysiological significance. Again, in contrast, GTN was reported to have no effect on mitochondrial respiration. In the same study, vasorelaxation induced by all agents was inhibited by the NO trap oxy-haemoglobin (oxyHb), although vasorelaxation by GTN was inhibited much less by oxyHb than by all other agents. In a third study reporting measurement of coronary vascular resistance in the isolated Langendorf...

PDE Inhibitors and Cardiovascular Disorders

With the discovery of the second messenger nitric oxide and its link to activation of guanylyl cyclase, there has been a renewed interest in inhibition of cGMP-selective PDEs as a means to produce vascular smooth muscle relaxation. While testing several compounds that inhibit the cGMP-specific PDE5, it was discovered that the corpus cavernous of the penis was particularly sensitive to these drugs. This observation has lead to the development of drugs useful in the treatment of penile erectile dysfunction (Licht, 1999). Sildenafil citrate (Viagra) is one of the most widely publicized drugs produced at the end of this century. Another area of potential use of PDE5 inhibitors is for the treatment of pulmonary hypertension (Beavo, 1995).

Identification And Coverage Of Sorption Sites And Some Critical Hydration Levels In The Sorption Isotherm

There has been some debate as to the sites of water sorption and the extent of coverage, particularly with regard to the participation of sites along the polypeptide backbone. Even the amount of bound water has been difficult to define unambiguously. The physical properties of water interacting with proteins have been studied with a variety of techniques, including dielectric relaxation methods (see Chapter 4), infrared and NMR spectroscopy, Rayleigh scattering of Mossbauer radiation (RSMR) (see Chapter 5), hydrodynamic methods as well as thermodynamic measurements (see reviews by Kuntz and Kauzmann 1 , Edsall and McKenzie 2 , Rupley and Careri 3 , Luscher-Mattli 33 , and the volume of Methods in Enzymology edited by Hirs and Timasheff 34 ). Most methods provide some estimate of the amount of water that interacts with the protein and that has structural or dynamic properties, as measured by the particular technique, that are different from those of bulk water. This water is termed...

Disorders of Swallowing

Nasopharyngeal Penetration

Sufficient tongue control to latch onto and maintain control of the nipple. Suckling deficits also manifest with weak and deficient tongue motion, inability to compress the nipple and early tiring (KrAmeR 1989). Oral motor dysfunction occurs with moderate or severe cerebral palsy and developmental delay. Incomplete buccal closure leads to drooling, and abnormal tongue and jaw motion (KrAmer 1989). Those neurologically impaired children unable to elevate the soft palate experience nasopharyngeal incoordination and nasopharyngeal reflux (Fig. 2.4). Occasional nasopharyngeal incoordination is most commonly due to transient swallowing incoordination. Retropharyngeal masses such as teratoma, lymphoma and abscess can rarely cause dysphagia. Cricopharyngeal achalasia, or failure of relaxation of the cricopharyngeus muscle, is most commonly secondary to gastroesophageal reflux. Signs of cri-copharyngeal achalasia include absent, delayed or incomplete opening or early closure of the sphincter....

Pdes As Targets For Pharmacological Intervention

Thea sinensis, Coffea arabica, and Theobroma cacao, and mention of the stimulating properties of these extracts is found in records of the most ancient civilizations. The active principles in these extracts are alkaloids called xanthines, the most potent being the-ophylline and caffeine. The effect of caffeine and theophylline on PDE activity was discovered soon after the discovery of cAMP. It was actually adopted as a diagnostic tool of activation of the cAMP-dependent pathway. Those cell functions that are potentiated by xanthines are most likely mediated by activation of the cyclic nucleotide pathway. More comprehensive studies have demonstrated that xanthines have additional effects on Ca2+ sequestration and on the adenosine pathway, but it is still accepted that a good portion of their stimulatory activity is due to the increase in cAMP that follows inhibition of the PDE activity. Treatment with xanthines produces a wide range of pharmacological effects, including stimulation of...

Multiple Energy Window Methods

The parameter b is a relaxation factor that controls the amount of feedback of the modification term into the correction and when b 0, the TEW technique becomes the DEW technique. The energy window used in the Clw Rsc term may be either of the two lower energy windows (Fig. 5.15c). In the implementation of Shao et al., the lower energy windows spanned the energies 385-450 keV and 350-450 keV, the calibration phantom was a 20 cm diameter uniform cylinder and the relaxation factor was 0.5 45 . As in the DEW technique, the ratios Robj and Rcalib and the modification factor M are calculated for each sino-gram element. The TEW method has many of the same advantages and drawbacks of the dual energy methods. However, it improves on the DEW method in particular by reducing the sensitivty of the scatter correction to variations in source distribution and size.

Endotheliumderived relaxing factors

Stimulation of intact endothelial cells by circulating neurotransmitters, hormones and substances derived from platelets and the coagulation system causes the release of a substance that induces relaxation of the underlying vascular smooth muscle (Furchgott and Zawadzki, 1980). Furthermore, mechanical forces such as shear stress, which are generated by changes in blood flow, induce endothelium-dependent vasodilatation, an important adaptive response during exercise. In 1980, Furchgott and Zawadzki first postulated the existence of an endothelium-derived relaxing factor (EDRF). The identity of the factor within the endothelium that mediated vascular relaxation was later found to be nitric oxide (NO) (Furchgott, 1988 Ignarro et al, 1988 Palmer et al, 1987). Vascular smooth muscle cell relaxation Vascular smooth muscle cell relaxation

Changes in Balance and Falls

Diagram Demonstrating Sleep Stages Eeg

Skilled movements (e.g., fine finger movements) are regulated in the brain by nerve fibers that originate in the motor cortex and form the pyramids in the medulla, hence the term pyramidal tracts. Grosser movements and posture are regulated by central nervous system (CNS) areas (e.g., basal ganglia) other than those connected with the pyramidal tracts, hence, by exclusion, the term extrapyramidal pathways. Coordination, adjustment, and smoothing of movements are regulated by the cerebellum, which receives impulses from several sensory receptors. Impulses from all of these brain structures ultimately determine the pattern and rate of discharge of the spinal motor neurons and neurons in motor nuclei of cranial nerves, thereby controlling somatic motor activity. Axons from these neurons form motor nerves that travel from the spinal cord to the various skeletal muscles throughout the body. Once the muscle has been reached, motor nerves synapse at the myoneural junction and transmit the...

Protein Mediators Of Biotransformation

Anaerobic conditions, generating a low flux of NO, but XOR was inactivated in the process. A more recent study of the XOR-mediated reduction of GTN and ISDN confirmed aspects of this work, but importantly, NO was not detectable as a product without the addition of thiols or ascorbate 207 . The thiol dependence and detection of nitrosothiols argue for XOR bioactivation of nitrates to nitrites, followed by non-enzymatic trapping by thiols to generate a nitrosothiol that itself generates NO. It was remarked that the maximum rate of NO production observed was less than 10 of that of nitrite hydrolysis to NO-. These observations are in accordance with the rapid trapping of nitrites by thiols and the rapid hydrolysis of NOGDN, the nitrite intermediate formed from GTN, which was first reported in 1994 173 . XOR itself catalyzes NO2 reduction to NO at the Mo site 166,206 , however, a leading role for XOR in vascular nitrate bioactivation is not supported by observations that the XOR...

Magnetic Resonance Imaging

Brain Has Structure Magnet

Precessional frequency increases as the field strength increases. Protons aligned with a static magnetic field precess at very high frequency around the axis of the external field. The precession frequency (Larmor frequency) is constant for a given type of atomic nucleus and the external field strength. All the hydrogen nuclei in the brain precess at the same frequency in the same field however, they precess with different phases. Thus, at a given moment different nuclei have reached different points in their rotation around the axis of the external field. Bloch and Purcell showed that if radiofrequency stimuli were supplied to the atoms at the right angle to the magnetic field, the nuclei absorbed energy and precessed at a wider and wider angle from the magnetic field. When the radiofrequency stimulus was discontinued, the precessing nuclei emitted a brief radiofrequency signal (i.e. magnetic resonance signal) at the same frequency as the precession frequency. If a pulse of...

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