Comparing the direct normal form and multiple scales methods through frequency detuning.

Approximate analytical methods, such as the multiple scales (MS) and direct normal form (DNF) techniques, have been used extensively for investigating nonlinear mechanical structures, due to their ability to offer insight into the system dynamics. A comparison of their accuracy has not previously been undertaken, so is addressed in this paper. This is achieved by computing the backbone curves of two systems: the single-degree-of-freedom Duffing oscillator and a non-symmetric, two-degree-of-freedom oscillator. The DNF method includes an inherent detuning, which can be physically interpreted as a series expansion about the natural frequencies of the underlying linear system and has previously been shown to increase its accuracy. In contrast, there is no such inbuilt detuning for MS, although one may be, and usually is, included. This paper investigates the use of the DNF detuning as the chosen detuning in the MS method as a way of equating the two techniques, demonstrating that the two can be made to give identical results up to ε 2 order. For the examples considered here, the resulting predictions are more accurate than those provided by the standard MS technique. Wolfram Mathematica scripts implementing these methods have been provided to be used in conjunction with this paper to illustrate their practicality.

Assessment of gastrointestinal health in racing Alaskan sled dogs using capsule endoscopy and inflammatory cytokines.

OBJECTIVES: Exercise-induced gastrointestinal syndrome occurs in dogs and people and might compromise athlete performance by increasing intestinal permeability and causing gastrointestinal erosions. Racing sled dogs often receive acid suppressant prophylaxis which decreases the incidence of gastric erosions induced by exercise. The objectives were to quantify intestinal injury by measuring serum pro-inflammatory cytokine concentrations before and after exercise and to evaluate gastrointestinal mucosa using video capsule endoscopy after exercise. MATERIALS AND METHODS: Prospective study of 12 racing Alaskan sled dogs receiving approximately 1 mg/kg omeprazole once daily from the day before the race until race completion. Blood was drawn before and 8 to 10 hours after an endurance race for the quantification of cytokines. Gastrointestinal tract mucosa was assessed with video capsule endoscopy immediately post-race. RESULTS: Eight of nine dogs (89%; 95% confidence interval 52 to 100%) had gastric erosions; all dogs (100%, 95% confidence interval 63 to 100%) had small intestinal erosions. Most of the dogs (seven of nine) had straw or foreign material present. Cytokine levels were not different from before to after the race. CLINICAL SIGNIFICANCE: Video capsule endoscopy identified gastrointestinal tract mucosal erosions after exercise in all dogs receiving once-daily omeprazole treatment, though other causes for the lesions besides exercise are possible.

Pyloric outflow obstruction secondary to sclerosing encapsulating peritonitis in a dog.

A 6-year-old, male neutered mixed breed dog was presented emergently with a three-week history of hyporexia, vomiting, diarrhoea and weight loss. Upon examination, the patient was dull, had generalised muscle atrophy, moderate abdominal pain and a mild amount of peritoneal effusion. A fluid-filled, distended, corrugated small bowel with marked gastroparesis and moderate peritoneal effusion was noted on abdominal ultrasonography. Endoscopy revealed hyperaemic and friable mucosa and a subjectively narrowed pylorus. Emergency exploratory celiotomy was performed due to worsening patient condition and revealed thick, diffuse, fibrous adhesions of the abdominal cavity. Based on these findings, sclerosing encapsulating peritonitis (SEP) was suspected. A large mass of omentum adjacent to the greater curvature of the stomach had caused a pyloric outflow obstruction. Adhesiolysis was attempted but was unsuccessful due to the friability of the small intestines. The dog was humanely euthanased under anaesthesia. A diagnosis of SEP was confirmed via necropsy. No underlying cause was identified. This is the first known case of a pyloric outflow obstruction secondary to SEP in a dog. Although rare, this condition should be considered as a differential for dogs with signs of a pyloric outflow obstruction with concurrent ascites and abdominal pain, hyporexia, vomiting and diarrhoea.

Muscle contraction and free energy transduction in biological systems.

Muscle contraction occurs when the actin and myosin filaments in muscle are driven past each other by a cyclic interaction of adenosine triphosphate (ATP) and actin with cross-bridges that extend from myosin. Current biochemical studies suggest that, during each adenosine triphosphatase cycle, the myosin cross-bridge alternates between two main conformations, which differ markedly in their strength of binding to actin and in their overall structure. Binding of ATP to the cross-bridge induces the weak-binding conformation, whereas inorganic phosphate release returns the cross-bridge to the strong-binding conformation. This cross-bridge cycle is similar to the kinetic cycle that drives active transport and illustrates the general principles of free energy transduction by adenosine triphosphatase systems.

Force appropriation of nonlinear structures.

Nonlinear normal modes (NNMs) are widely used as a tool for developing mathematical models of nonlinear structures and understanding their dynamics. NNMs can be identified experimentally through a phase quadrature condition between the system response and the applied excitation. This paper demonstrates that this commonly used quadrature condition can give results that are significantly different from the true NNM, in particular, when the excitation applied to the system is limited to one input force, as is frequently used in practice. The system studied is a clamped-clamped cross-beam with two closely spaced modes. This paper shows that the regions where the quadrature condition is (in)accurate can be qualitatively captured by analysing transfer of energy between the modes of the system, leading to a discussion of the appropriate number of input forces and their locations across the structure.

Identifying the significance of nonlinear normal modes.

Nonlinear normal modes (NNMs) are widely used as a tool for understanding the forced responses of nonlinear systems. However, the contemporary definition of an NNM also encompasses a large number of dynamic behaviours which are not observed when a system is forced and damped. As such, only a few NNMs are required to understand the forced dynamics. This paper firstly demonstrates the complexity that may arise from the NNMs of a simple nonlinear system-highlighting the need for a method for identifying the significance of NNMs. An analytical investigation is used, alongside energy arguments, to develop an understanding of the mechanisms that relate the NNMs to the forced responses. This provides insight into which NNMs are pertinent to understanding the forced dynamics, and which may be disregarded. The NNMs are compared with simulated forced responses to verify these findings.

Evaluating Quality and Adequacy of Gastrointestinal Samples Collected using Reusable or Disposable Forceps.

BACKGROUND: Sample quality of gastrointestinal endoscopic biopsies is of paramount importance for accurate histological diagnosis. Many veterinary practices use reusable forceps as a result of perceived decreased cost. With reusable forceps, it remains unknown whether sample quality declines with repeated use and becomes inferior to single-use forceps and is therefore more or less cost effective than single-use forceps. HYPOTHESIS/OBJECTIVES: The study hypothesis was that reusable forceps sample quality would deteriorate after repeated use as compared to single-use forceps. ANIMALS: Sixty-five dogs undergoing gastrointestinal endoscopy for diagnostic investigations at the Hospital for Small Animals, Edinburgh University. METHOD: A prospective, pathologist-blinded study comparing single-use and reusable alligator standard cup biopsy forceps (Olympus 2.0 mm 1550 mm) with 5 randomized reusable forceps. Sample quality (stomach, duodenum, ileum, and colon) was assessed by a single pathologist using the WSAVA guidelines. RESULTS: There was no difference in the adequacy, depth, villi number, or crush artifact in the 4 intestinal areas between forceps type with at least 10, and up to 15, repeated uses of the reusable forceps. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates that reusable cup biopsy forceps provide equivalent biopsy quality after repeated uses to single-use forceps and are cost effective at 10-case use.

Out-of-unison resonance in weakly nonlinear coupled oscillators.

Resonance is an important phenomenon in vibrating systems and, in systems of nonlinear coupled oscillators, resonant interactions can occur between constituent parts of the system. In this paper, out-of-unison resonance is defined as a solution in which components of the response are 90° out-of-phase, in contrast to the in-unison responses that are normally considered. A well-known physical example of this is whirling, which can occur in a taut cable. Here, we use a normal form technique to obtain time-independent functions known as backbone curves. Considering a model of a cable, this approach is used to identify out-of-unison resonance and it is demonstrated that this corresponds to whirling. We then show how out-of-unison resonance can occur in other two degree-of-freedom nonlinear oscillators. Specifically, an in-line oscillator consisting of two masses connected by nonlinear springs-a type of system where out-of-unison resonance has not previously been identified-is shown to have specific parameter regions where out-of-unison resonance can occur. Finally, we demonstrate how the backbone curve analysis can be used to predict the responses of forced systems.

Binding under a molecular "umbrella" as a cooperative statistical mechanical system: tropomyosin-actin-myosin as an example.

We Study models in which initial ligand molecules can bind on a linear array of sites only by lifting or moving an adjacent polymer molecule, over a range of a few binding sites, into a state of higher free energy. This inhibits the initial binding but subsequent ligand molecules can then bind more easily under the "umbrella" already lifted in the initial binding (a cooperative effect). Three subjects are considered: cooperative properties of a general model in which, besides the "umbrella" effect, the polymer is divided into m-site long segments, with interactions between the ends of these segments (section 3); application of this model to tropomyosin-troponin-myosin (section (a cooperative effect). Three subjects are considered: cooperative properties of a general model in which, besides the "umbrella" effect, the polymer is divided into m-site long segments, with interactions between the ends of these segments (section 3); application of this model to tropomyosin-troponin-myosin (section (a cooperative effect). Three subjects are considered: cooperative properties of a general model in which, besides the "umbrella" effect, the polymer is divided into m-site long segments, with interactions between the ends of these segments (section 3); application of this model to tropomyosin-troponin-myosin (section 2); and cooperative properties of simpler models in which the polymer is not divided into segments though the "umbrella" can have various ranges (section 4).

A theoretical study of cooperative dual linear aggregation and the vernier effect.

An introductory theoretical study is presented of cooperative dual linear aggregation, originating from a surface. That is, two kinds of molecules aggregate in side-by-side strands; lateral interactions cause the aggregation in the two strands to be cooperative. The vernier effect is a special case that is given particular attention: if the two kinds of molecules have different lengths, there will be certain combinations of numbers of molecules that will give the two strands the same length (a 'vernier structure'). Such a structure has extra thermodynamic and kinetic stability, literally because there are no loose ends. The increased lifetime of a vernier structure is, however, not very impressive unless some additional feature is incorporated into the model to enhance further such a structure. Aligned multi-stranded tubular aggregates are also discussed.

Theoretical considerations in the equilibrium binding of myosin fragments on F-actin.

In a previous paper, equilibrium ocnstants for the binding of myosin fragments onto F-actin were assumed known and the statistical problems encountered when the actin sites are occupied to an arbitrary fractional extent were analyzed. The object of the present paper is to attempt to understand the observed order of magnitude of these equilibrium constants in terms of the statistical mechanical degrees of freedom involved. That is, we examine here the equilibrium constants themselves rather than the statistical consequences of the equilibrium constants. The treatment given amounts to a semi-quantitative sketch or outline of the problem. Structural details are much too uncertain to warrant a careful and rigorous treatment at this time. But the discussion suffices to establish the essential qualitative features of the problem. The procedure used is to examine the important equilibrium constants, one at a time, in terms of the factors (partition functions) that contribute to each constant, together with numerical estimates for these factors.

The cone threshold: spatial interactions of rod and cone adapting signals.

Steady small blue adapting fields that stimulated only rods produced large threshold elevations for a superimposed tiny red flash that stimulated cones. The threshold elevation differed considerably between observers, confirming the results of Buck (Topical Meeting on Recent Advances in Vision, abstract in Technical Digest, 1980; Invest. Ophthal, visual Sci., Suppl. 20, 207, 1981). A red annulus that stimulated cones reduced slightly the threshold elevation produced by the small rod adapting field. Similarly, when the cone threshold was elevated by a small red field that stimulated only cones, a blue annulus that stimulated rods slightly reduced the threshold of the red cone test flash. These effects, although weak, demonstrate lateral sensitizing interactions between a cone center field and rod annulus, and vice versa, when the cone threshold is assessed with a tiny red flash.

An assessment of prolonged reactivity of seven monoclonal antibodies against CX-1 tumor xenografts using a hand-held gamma-detecting probe.

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.

Evaluation of urethral stent placement for benign urethral obstructions in dogs.

BACKGROUND: Benign urethral obstructions (BUO) in dogs result in substantial morbidity because of challenges with conventional therapies. Treatment of malignant urethral obstructions with intraluminal urethral stents is reported to successfully relieve obstructions. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy and outcome of urethral stent placement for treatment of BUO in dogs. ANIMALS: Eleven client-owned animals with urethral stents placed for treatment of BUO. METHODS: Retrospective study in which medical records were reviewed in dogs diagnosed with BUO and treated with a metallic urethral stent. Data collected included signalment, cause of benign obstruction, procedure time, size and type of stent, complications, and short- and long-term outcome. RESULTS: Eleven dogs with 15 urethral stents were included. Intraluminal urethral stent(s) relieved the obstructions in all dogs. Four dogs had 2 stents placed in separate procedures because of incomplete patency after treatment (n = 1), inadvertent compression of the stent (n = 1), or tissue ingrowth through the stent (n = 2). The median continence score after stent placement was 10 of 10 (range 3-10) with 6 dogs being continent, 3 mildly incontinent, and 1 each moderately and severely incontinent. All owners considered their dog to have an excellent long-term clinical outcome with long-term urethral patency. The median follow-up time was 24 months (range 4-48). CONCLUSIONS AND CLINICAL IMPORTANCE: Urethral stents appear to be an effective treatment for benign urinary obstructions. Moderate to severe incontinence developed in a minority (12.5%) of dogs. Stents relieved obstructions in all dogs with an excellent long-term outcome.

The effect of tramadol and indomethacin coadministration on gastric barrier function in dogs.

BACKGROUND: Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown. HYPOTHESIS/OBJECTIVES: That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid-injured, indomethacin-treated, and tramadol-treated mucosa. ANIMALS: Gastric mucosa of 10 humanely euthanized shelter dogs. METHODS: Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified. RESULTS: Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E2 (acid-injured PGE2 : 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE2 : 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B2 (acid-injured TXB2 : 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB2 : 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect (PGE2 P = .713, TXB2 P = .194). Neither drug had an effect on cyclooxygenase expression (COX-1 P = .743, COX-2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration. CONCLUSIONS AND CLINICAL IMPORTANCE: There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.