bluuebunny/crossref_metadata_2025 huggingface dataset:
Simvastatin Induces Heme Oxygenase-1
Authors: Lee Tzong-Shyuan , Chang Chih-Chieh , Zhu Yi , Shyy John Y.-J.
Published: August 2004

Background—

Evidence from experimental and clinical studies indicates that statins can protect the vessel wall through cholesterol-independent mechanisms. The “pleiotropic” effects include the prevention of inflammation and proliferation of vascular cells. Here, we studied whether heme oxygenase-1 (HO-1), an important cytoprotective molecule, is induced by simvastatin and the role of HO-1 in the pleiotropic effects of simvastatin.

Methods and Results—

Human and rat aortic smooth muscle cells treated with simvastatin showed an elevated level of HO-1 for up to 24 hours. The induction of HO-1 by simvastatin was not found in cultured endothelial cells and macrophages. Injecting C57BL/6J mice intraperitoneally with simvastatin increased the level of HO-1 in vascular SMCs (VSMCs) in the tunica media. Treating VSMCs with zinc protoporphyrin, an HO-1 inhibitor, or HO-1 small interfering RNA (siRNA) blocked the antiinflammatory effect of simvastatin, including the inhibition of nuclear factor-κB activation and nitric oxide production. Blockade of HO-1 also abolished the simvastatin-induced p21

Waf1

and the associated antiproliferative effect. Simvastatin activated p38 and Akt in VSMCs, and the respective inhibitor of p38 and phosphoinositide 3-kinase (PI3K) greatly reduced the level of simvastatin-induced HO-1, which suggests the involvement of p38 and the PI3K-Akt pathway in HO-1 induction.

Conclusions—

Simvastatin activates HO-1 in VSMCs in vitro and in vivo. The antiinflammatory and antiproliferative effects of simvastatin occur largely through the induced HO-1.
Beyond Restenosis
Authors: Cutlip Donald E. , Chhabra Amit G. , Baim Donald S. , Chauhan Manish S. , Marulkar Sachin , Massaro Joseph , Bakhai Ameet , Cohen David J. , Kuntz Richard E. , Ho Kalon K.L.
Published: August 2004

Background—

In the first year after coronary stent implantation, clinical failures are driven mainly by procedural complications and restenosis, but the subsequent relative contributions of restenosis and disease progression to late failures are less clear.

Methods and Results—

We observed 1228 patients for 5 years after the implantation of stents as part of pivotal second-generation coronary stent trials. Clinical events of death, myocardial infarction, repeat revascularization, and repeat hospitalization for acute coronary syndrome or congestive heart failure were attributed to the index stented (target) lesion or other distinct sites (either in the target or other coronary vessels) and further classified as procedural, restenosis, or nonrestenosis. During the first year the hazard rate was 18.3% for target-lesion events and 12.4% for events unrelated to the target lesion. After the first year the average annual hazard rate was 1.7% for target-lesion events and 6.3% for nontarget-lesion events. By the fifth year, restenosis events occurred in 20.3% of patients, whereas 30-day procedural complications or later nonrestenosis events occurred in 37.9%, including 11.4% who also experienced a restenosis event, for a combined cumulative event rate of 46.4%. Diabetes mellitus and multivessel disease were independently associated with increased risk for both restenosis and nonrestenosis events.

Conclusion—

In a low-risk clinical trial population, the clinical outcome beyond 1 year after stenting is determined by a high rate of events related to disease progression in segments other than the stented lesion, which itself remains relatively stable.
Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension
Authors: Velez-Roa Sonia , Ciarka Agnieszka , Najem Boutaina , Vachiery Jean-Luc , Naeije Robert , van de Borne Philippe
Published: August 2004

Background—

This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH.

Methods and Results—

We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (Sa
o
2
) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O
2
was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Compared with the controls, the PAH patients had increased MSNA (67±4 versus 40±3 bursts per minute;
P
<0.0001) and HR (82±4 versus 68±3 bpm;
P
=0.02). MSNA in the PAH patients was correlated with HR (
r
=0.64,
P
=0.006), Sa
o
2
(
r
=−0.53,
P
=0.03), the presence of pericardial effusion (
r
=0.51,
P
=0.046), and NYHA class (
r
=0.52,
P
=0.033). The PAH patients treated with prostacyclin derivatives had higher MSNA (
P
=0.009), lower Sa
o
2
(
P
=0.01), faster HR (
P
=0.003), and worse NYHA class (
P
=0.04). Plasma catecholamines were normal. Peripheral chemoreflex deactivation with hyperoxia increased Sa
o
2
(91.7±1% to 98.4±0.2%;
P
<0.0001) and decreased MSNA (67±5 to 60±4 bursts per minute;
P
=0.0015), thereby correcting approximately one fourth of the difference between PAH patients and controls.

Conclusions—

We report for the first time direct evidence of increased sympathetic nerve traffic in advanced PAH. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.
Long-Term Outcome in Elderly Patients With Chronic Angina Managed Invasively Versus by Optimized Medical Therapy
Authors: Pfisterer Matthias
Published: August 2004

Background—

There are no prospective trial data on long-term outcomes in 80-year-old patients with chronic angina with regard to antiischemic therapy.

Methods and Results—

To assess long-term survival and quality of life (QoL) in patients from the
T
rial of
I
nvasive versus
M
edical Therapy in the
E
lderly (TIME), all 276 1-year survivors (of a total 301 patients) were contacted after a median of 3.1 years (range, 1.1 to 5.9 years). At baseline, patients were 80±4 years old, 42% were women, and they were designated as being in angina class 3.2±0.7, despite their taking 2.5±0.7 antiischemic drugs. Patients were randomized to an invasive (n=153) or an optimized medical (n=148) strategy. Survival of invasive-strategy versus medical-strategy patients was 91.5% versus 95.9% after 6 months, 89.5% versus 93.9% after 1 year, and 70.6% versus 73.0% after 4.1 years (
P
=NS). Mortality was independently increased in patients ≥80 years of age, with prior heart failure, ejection fraction ≤0.45, and ≥2 comorbidities, and without revascularization within the first year. Revascularization within the first year improved survival in invasive-strategy (
P
=0.07) and medical-strategy (
P
<0.001) patients. The early benefit of both treatments in angina relief and QoL was maintained long term, but freedom from major events remained higher in invasive-strategy versus medical-strategy patients (39% versus 20%,
P
<0.0001).

Conclusions—

Long-term survival was similar for patients assigned to invasive and medical treatment. The benefits of both treatments in angina relief and improvement in QoL were maintained, but nonfatal events occurred more frequently in patients assigned to medical treatment. Irrespective of whether patients were catheterized initially or only after drug therapy failure, their survival rates were better if they were revascularized within the first year.
Plasma Levels of Cholesteryl Ester Transfer Protein and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
Authors: Boekholdt S. Matthijs , Kuivenhoven Jan-Albert , Wareham Nicholas J. , Peters Ron J.G. , Jukema J. Wouter , Luben Robert , Bingham Sheila A. , Day Nicholas E. , Kastelein John J.P. , Khaw Kay-Tee
Published: August 2004

Background—

Low plasma levels of cholesteryl ester transfer protein (CETP) are associated with elevated levels of HDL cholesterol (HDL-C), but it remains unclear whether this translates into a concomitant reduction in the risk of coronary artery disease (CAD). Evidence exists that the effect of CETP depends on metabolic context, in particular on triglyceride levels.

Methods and Results—

A nested case-control study was performed in the prospective EPIC-Norfolk cohort study. Cases were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during follow-up. Control subjects were matched by age, sex, and enrollment time. CETP levels were not significantly different between cases and controls (4.0±2.2 versus 3.8±2.1 mg/L,
P
=0.07). CETP levels were significantly related to plasma levels of total cholesterol, LDL cholesterol, and HDL-C. The risk of CAD increased with increasing CETP quintiles (
P
for linearity=0.02), such that subjects in the highest quintile had an adjusted OR of 1.43 (95% CI 1.03 to 1.99,
P
=0.03) versus those in the lowest. Among individuals with triglyceride levels below the median (1.7 mmol/L), no relationship between CETP levels and CAD risk was observed (
P
for linearity=0.5), but this relationship was strong among those with high triglyceride levels (
P
for linearity=0.02), such that those in the highest CETP quintile had an OR of 1.87 (95% CI 1.06 to 3.30,
P
=0.02).

Conclusions—

Elevated CETP levels are associated with an increasing risk of future CAD in apparently healthy individuals, but only in those with high triglyceride levels.
Downregulation of Matrix Metalloproteinases and Collagens and Suppression of Cardiac Fibrosis by Inhibition of the Proteasome
Authors: Meiners Silke , Hocher Berthold , Weller Andrea , Laule Michael , Stangl Verena , Guenther Christoph , Godes Michael , Mrozikiewicz Alexander , Baumann Gert , Stangl Karl
Published: August 2004

Myocardial remodeling is an adaptive response of the myocardium to several forms of stress culminating in cardiac fibrosis, left ventricular dilation, and loss of contractility. The remodeling processes of the extracellular matrix are controlled by matrix metalloproteinases, which are in turn regulated by growth factors and inflammatory cytokines. The inflammatory transcription factor nuclear factor κB has been implicated in the transcriptional regulation of several matrix metalloproteinases. Because activation of nuclear factor κB in turn is essentially controlled by the ubiquitin-proteasome system, we investigated the hypothesis that inhibition of the proteasome may prevent activation of matrix metalloproteinases. We demonstrate here that inhibition of the proteasome in rat cardiac fibroblasts suppressed not only expression of matrix metalloproteinases 2 and 9, but also expression of collagen Iα1, Iα2, and IIIα1 as determined by in-gel zymography and real-time reverse transcription–polymerase chain reaction. Moreover, myocardial expression of matrix metalloproteinases and collagens was effectively suppressed by systemic treatment of spontaneously hypertensive rats over 12 weeks with the proteasome inhibitor MG132, which resulted in a marked reduction of cardiac fibrosis (−38%) compared with control animals. We conclude that inhibition of the ubiquitin-proteasome system may provide a new and attractive tool to interfere with collagen and matrix metalloproteinase expression, and therefore might be of possible use in the therapy of myocardial remodeling.
Dual diagnosis: management within a psychosocial context
Authors: Abou-Saleh Mohammed T.
Published: August 2004

Recent developments in UK government policy have highlighted the unmet needs of people with dual diagnosis (comorbidity of substance misuse and psychiatric disorder, particularly severe mental illness). Advances in assessment techniques and diagnostic practice have informed the treatment of comorbidity and improved its outcome. There is growing evidence for the effectiveness of psychosocial interventions such as motivational interviewing and cognitive–behavioural therapy, mostly from US studies. However, within the secondary care provided by addiction and general psychiatric services there are serious implementation barriers related to service organisation, staffing levels, training and – most importantly – the difficulties of engaging people with severe mental illness and comorbid substance misuse in treatment. The evidence for the effectiveness of psychosocial treatments and models of service is reviewed and challenges for optimal practice in the UK are highlighted.
Psychotherapies with older people: an overview
Authors: Hepple Jason
Published: August 2004

Psychotherapies with older people have been slow to develop, both theoretically and operationally, in the UK. This is due to ageism and the predominance of models of psychological development relevant to children and younger adults. Despite this, many have applied their practice and skills to psychological work in old age psychiatry, countering the dominance of the ‘organic’ model. An evidence and practice base exists to suggest that cognitive–behavioural therapy, interpersonal therapy, cognitive analytic therapy, psychodynamic and systemic approaches can help in a range of psychiatric problems in older people, including affective disorders, personality disorders and dementia. The inclusion of older people in existing psychotherapy services and the development of networks of practitioners whose support and supervision are encouraged are likely to be positive ways forward.
Drug treatment for personality disorders
Authors: Tyrer Peter , Bateman Anthony W.
Published: August 2004

There is some evidence that antidepressants, particularly the selective serotonin reuptake inhibitors and the monoamine oxidase inhibitors, have some benefits in the management of borderline personality disorder, and lesser evidence (partly because of limited trial data) for the benefits of antipsychotic drugs and mood stabilisers. There is not sufficient distinction between the different personality disorders to recommend that any one disorder should be treated by any one drug, and successful treatment is dependent on careful management, sensitive to the patient's expectations.
Stimulant psychosis: systematic review
Authors: Curran Catherine , Byrappa Neetha , McBride Andrew
Published: August 2004

Background

Psychosis associated with stimulant use is an increasing problem, but there is little research evidence about the nature of the problem and its management.

Aims

To critically review the literature on stimulant psychosis and sensitisation.

Method

Systematic review of studies that have investigated stimulant use and psychosis in humans. The main outcome measures were increases in psychosis with stimulant use, and differences between stimulant users and non-users.

Results

Fifty-four studies met the inclusion criteria. Experimental studies show that a single dose of a stimulant drug can produce a brief increase in psychosis ratings (a ‘response’) in 50–70% of participants with schizophrenia and preexisting acute psychotic symptoms, unaffected by the presence of antipsychotic medication. Those with schizophrenia who do not have acute psychotic symptoms respond, but less frequently (30%). There has been little research into the longer-term effects of use.

Conclusions

Compliance with antipsychotic medication by someone with schizophrenia will not prevent a relapse or worsening of psychotic symptoms if stimulants are used. Low-dose antipsychotic treatment may be beneficial in stimulant users, to prevent sensitisation.
Cell density and cortical thickness in Heschl's gyrus in schizophrenia, major depression and bipolar disorder
Authors: Cotter David , Mackay Daniel , Frangou Sophia , Hudson Lance , Landau Sabine
Published: August 2004

There is evidence that the superior temporal gyrus and Heschl's gyrus within it are implicated in schizophrenia. We investigated neuronal and glial cell density and cortical thickness within Heschl's gyrus, using the optical disector to estimate cell density within cortical layers 3 and 5 in tissue derived postmortem from people with diagnoses of major depressive disorder, schizophrenia and bipolar disorder, compared with normal controls (n=15 per group). No significant difference in neuronal or glial cell density or in cortical thickness was observed between the groups; our findings therefore provide no support for the presence of cellular pathology within Heschl's gyrus in schizophrenia.
Admission patterns of patients with personality disorder
Authors: Dasgupta Pritha , Barber Joan
Published: August 2004

Aims and Method

To examine the prevalence and admission patterns of patients with personality disorder admitted to a Scottish general adult psychiatry service. We carried out a retrospective case-note study of patients identified from the computerised patient administration system. A subgroup of patients was identified as having a longer in-patient stay. Their admission pattern over the preceding 4 years was studied further.

Results

Sixty-two of 844 patients admitted had personality disorder. Thirty-nine had a primary diagnosis of personality disorder, 19 had an additional diagnosis of psychiatric disorder and 12 of alcohol or substance misuse. Within the subgroup admitted for longer in 2001, patterns of few/brief and numerous/often lengthy admissions were noted in earlier years.

Clinical Implications

Personality disorder occurs in approximately 7% of admissions to general adult psychiatry beds. Many have additional diagnoses of psychiatric disorder, or substance or alcohol misuse further complicating their treatment.
Inhalation induction with sevoflurane for electroconvulsive therapy: a case series
Authors: Palmer James , Khalil Mohsen , Meagher David
Published: August 2004

Aims and Method

Until 1999, the most common drug for induction of anaesthesia for electroconvulsive therapy (ECT) in the UK was methohexital. Cessation of production left few choices of induction agent. Increased use of sevoflurane in short procedures suggests that it might be suitable as a sole agent for anaesthesia in ECT. We therefore induced anaesthesia in five consecutive patients undergoing ECT to assess sevoflurane's potential for this use. We recorded vital signs, needle phobia, face-mask toleration, duration of induction, seizure duration and recovery variables.

Results

Anaesthesia was successfully induced in all patients without difficulty. One patient experienced mild hypoxia following the seizure. Seizure duration ranged from 24 to 72 seconds. Recovery times to eye opening and times to ‘ward’ fitness were acceptable.

Clinical Implications

Sevoflurane may be a suitable alternative for induction of anaesthesia for ECT.
Reading about self-help for schizophrenia
Authors: Kingdon David , Murray Paul , Doyle Elaine
Published: August 2004

There is a deluge of written information for users and carers being produced about schizophrenia, which shows no sign of abating, so this article makes no attempt to be comprehensive. It would be out-of-date by the time of publication and would inevitably miss leaflets cherished by individual psychiatrists, mental health workers, users and carers. However, remarkably few up-to-date books exist and this issue will be discussed later in the article.
Recurrence properties of autoregressive processes with super-heavy-tailed innovations
Authors: Zeevi Assaf , Glynn Peter W.
Published: August 2004

This paper studies recurrence properties of autoregressive (AR) processes with ‘super-heavy-tailed’ innovations. Specifically, we study the case where the innovations are distributed, roughly speaking, as log-Pareto random variables (i.e. the tail decay is essentially a logarithm raised to some power). We show that these processes exhibit interesting and somewhat surprising behaviour. In particular, we show that AR(1) processes, with the usual root assumption that is necessary for stability, can exhibit null-recurrent as well as transient dynamics when the innovations follow a log-Cauchy-type distribution. In this regime, the recurrence classification of the process depends, somewhat surprisingly, on the value of the constant pre-multiplier of this distribution. More generally, for log-Pareto innovations, we provide a positive-recurrence/null-recurrence/transience classification of the corresponding AR processes.
Large deviations for supercritical multitype branching processes
Authors: Jones Owen Dafydd
Published: August 2004

Large deviation results are obtained for the normed limit of a supercritical multitype branching process. Starting from a single individual of type i, let L[i] be the normed limit of the branching process, and let be the minimum possible population size at generation k. If is bounded in k (bounded minimum growth), then we show that P(L[i] ≤ x) = P(L[i] = 0) + xαF*[i](x) + o(xα) as x → 0. If grows exponentially in k (exponential minimum growth), then we show that −log P(L[i] ≤ x) = x−β/(1−β) G*[i](x) + o (x−β/(1−β)) as x → 0. If the maximum family size is bounded, then −log P(L[i] > x) = xδ/(δ−1)H*[i](x) + o(xδ/(δ−1)) as x → ∞. Here α, β and δ are constants obtained from combinations of the minimum, maximum and mean growth rates, and F*, G* and H* are multiplicatively periodic functions.
An optimal trade-off between content freshness and refresh cost
Authors: Ling Yibei , Mi Jie
Published: August 2004

Caching is an effective mechanism for reducing bandwidth usage and alleviating server load. However, the use of caching entails a compromise between content freshness and refresh cost. Constant refreshing allows a high degree of content freshness at a greater cost of system resource. Conversely, too little refreshing reduces content freshness but saves the cost of resource usage. To address the freshness-cost problem, we formulate the refresh scheduling problem with a generic cost model and use this cost model to determine an optimal refresh frequency that gives the best trade-off between refresh cost and content freshness. We prove the existence and uniqueness of an optimal refresh frequency under the assumptions that the arrival of updated content is Poisson and the age-related cost monotonically increases with decreasing freshness. In addition, we provide an analytic comparison of system performance under fixed refresh scheduling and random refresh scheduling, showing that two refresh schedulings with the same average refresh frequency are mathematically equivalent in terms of the long-run average cost.
Burn-in and covariates
Authors: Ebrahimi Nader
Published: August 2004

Burn-in is a widely used engineering procedure useful for eliminating ‘weak’ items and consequently improving the quality of remaining items. The quality of items can be measured via various performance characteristics. In the present paper we develop new performance criteria for the burn-in method. Our criteria not only take into account the reliability of an item, they also incorporate covariates.
Markov-renewal fluid queues
Authors: Latouche Guy , Takine Tetsuya
Published: August 2004

We consider a fluid queue controlled by a semi-Markov process and we apply the Markov-renewal approach developed earlier in the context of quasi-birth-and-death processes and of Markovian fluid queues. We analyze two subfamilies of semi-Markov processes. In the first family, we assume that the intervals during which the input rate is negative have an exponential distribution. In the second family, we take the complementary case and assume that the intervals during which the input rate is positive have an exponential distribution. We thoroughly characterize the structure of the stationary distribution in both cases.
Cyclic queueing networks with subexponential service times
Authors: Ayhan H. , Palmowski Z. , Schlegel S.
Published: August 2004

For aK-stage cyclic queueing network withNcustomers and general service times, we provide bounds on thenth departure time from each stage. Furthermore, we analyze the asymptotic tail behavior of cycle times and waiting times given that at least one service-time distribution is subexponential.
The annihilating process on random trees and the square lattice
Authors: Sudbury Aidan
Published: August 2004

An annihilating process is an interacting particle system in which the only interaction is that a particle may kill a neighbouring particle. Since there is no birth and no movement, once a particle has no neighbours its site remains occupied for ever. The survival probability is calculated for a random tree and for the square lattice. A connection is made between annihilating processes and the adsorption of molecules onto surfaces. A one-dimensional adsorption problem is solved in the case in which the two neighbours do not act independently.
Analysis of generalized processor-sharing systems with two classes of customers and exponential services
Authors: Guillemin Fabrice , Pinchon Didier
Published: August 2004

We derive in this paper closed formulae for the joint probability generating function of the number of customers in the two FIFO queues of a generalized processor-sharing (GPS) system with two classes of customers arriving according to Poisson processes and requiring exponential service times. In contrast to previous studies published on the GPS system, we show that it is possible to establish explicit expressions for the generating functions of the number of customers in each queue without calling for the formulation of a Riemann–Hilbert problem. We specifically prove that the problem of determining the unknown functions due to the reflecting conditions on the boundaries of the positive quarter plane can be reduced to a Poisson equation. The explicit formulae are then used to derive some characteristics of the GPS system (in particular the tails of the probability distributions of the numbers of customers in each queue).
A symmetrized Euler scheme for an efficient approximation of reflected diffusions
Authors: Bossy Mireille , Gobet Emmanuel , Talay Denis
Published: August 2004

In this article, we analyse the error induced by the Euler scheme combined with a symmetry procedure near the boundary for the simulation of diffusion processes with an oblique reflection on a smooth boundary. This procedure is easy to implement and, in addition, accurate: indeed, we prove that it yields a weak rate of convergence of order 1 with respect to the time-discretization step.
Random dynamical systems with jumps
Authors: Horbacz Katarzyna
Published: August 2004

We consider random dynamical systems with randomly chosen jumps on infinite-dimensional spaces. The choice of deterministic dynamical systems and jumps depends on a position. The system generalizes dynamical systems corresponding to learning systems, Poisson driven stochastic differential equations, iterated function system with infinite family of transformations and random evolutions. We will show that distributions which describe the dynamics of this system converge to an invariant distribution. We use recent results concerning asymptotic stability of Markov operators on infinite-dimensional spaces obtained by T. Szarek.
Some properties of ageing notions based on the moment-generating-function order
Authors: Li Xiaohu
Published: August 2004

Classes of life distributions based on the moment-generating-function order are investigated in this paper. It is shown firstly that the class ℳ is closed under both convex linear combination and geometric compounding. Secondly, the class NBUmg (new better than used in the moment-generating-function order) is proved to be closed under increasing star-shaped transformations. Finally, the interplay between the stochastic comparison of the excess lifetime of a renewal process and the NBUmg interarrivals is studied.
Ground reaction forces in horses trotting up an incline and on the level over a range of speeds
Authors: Dutto Darren J. , Hoyt Donald F. , Cogger Edward A. , Wickler Steven J.
Published: August 2004

Although the forces required to support the body mass are not elevated when moving up an incline, kinematic studies, in vivo tendon and bone studies and kinetic studies suggest there is a shift in forces from the fore-to the hindlimbs in quadrupeds. However, there are no whole-animal kinetic measurements of incline locomotion. Based on previous related research, we hypothesized that there would be a shift in forces to the hindlimb. The present study measured the force produced by the fore- and hindlimbs of horses while trotting over a range of speeds (2.5 to 5 m s–1) on both level and up an inclined (10%) surface.

On the level, forelimb peak forces increased with trotting speed, but hindlimb peak force remained constant. On the incline, both fore- and hindlimb peak forces increased with speed, but the sum of the peak forces was lower than on the level. On the level, over the range of speeds tested, total force was consistently distributed between the limbs as 57% forelimb and 43%hindlimb, similar to the weight distribution of the horses during static weight tests. On the incline, the force distribution during locomotion shifted to 52% forelimb and 48% hindlimb.

Time of contact and duty factor decreased with speed for both limbs. Time of contact was longer for the forelimb than the hindlimb, a finding not previously reported for quadrupeds. Time of contact of both limbs tended to be longer when traveling up the incline than on the level, but duty factor for both limbs was similar under both conditions. Duty factor decreased slightly with increased speed for the hindlimb on the level, and the corresponding small, predicted increase in peak vertical force could not be detected statistically.
Biomechanics of quadrupedal walking: how do four-legged animals achieve inverted pendulum-like movements?
Authors: Griffin Timothy M. , Main Russell P. , Farley Claire T.
Published: August 2004

Walking involves a cyclic exchange of gravitational potential energy and kinetic energy of the center of mass. Our goal was to understand how the limbs of walking quadrupeds coordinate the vertical movements of the fore and hind quarters to produce these inverted pendulum-like movements. We collected kinematic and ground reaction force data from dogs walking over a range of speeds. We found that the fore and hind quarters of dogs behaved like two independent bipeds, each vaulting up and over its respective support limb. The center of mass moved up and down twice per stride, like a single walking biped, and up to 70% of the mechanical energy required to lift and accelerate the center of mass was recovered via the inverted pendulum mechanism. To understand how the limbs produce these center of mass movements, we created a simple model of two independent pendulums representing the movements of the fore and hind quarters. The model predicted that the fore and hind quarter movements would completely offset each other if the fore limb lagged the hind limb by 25% of the stride time and body mass was distributed equally between the fore and hind quarters. The primary reason that dogs did not walk with a flat trajectory of the center of mass was that each fore limb lagged its ipsilateral hind limb by only 15% of the stride time and thereby produced time periods when the fore and hind quarters moved up or down simultaneously. The secondary reason was that the fore limbs supported 63% of body mass. Consistent with these experimental results, the two-pendulum model predicts that the center of mass will undergo two fluctuations per stride cycle if limb phase is less than 25% and/or if the total mass is not distributed evenly between the fore or hind quarters.
Distance and force production during jumping in wild-type and mutantDrosophila melanogaster
Authors: Zumstein Nina , Forman Oliver , Nongthomba Upendra , Sparrow John C. , Elliott Christopher J. H.
Published: August 2004

In many insects renowned for their jumping ability, elastic storage is used so that high forces can be developed prior to jumping. We have combined physiological, behavioural and genetic approaches to test whether elastic energy storage makes a major contribution to jumping in Drosophila.

We describe a sensitive strain gauge setup, which measures the forces produced by tethered flies through their mesothoracic legs. The peak force produced by the main jumping muscle of female flies from a wild-type(Canton-S) strain is 101±4.4 μN [and this is indistinguishable from a second wild-type (Texas) strain]. The force takes 8.2 ms to reach its peak. The peak force is not affected significantly by altering the leg angle (femur–tibia joint angle) in the range of 75–120°, but the peak force declines as the leg is extended further.

Measurements of jumping ability (distance jumped) showed that female Drosophila (with their wings removed) of two wild-type strains,Canton-S and Texas, produced jumps of 28.6±0.7 and 30.2±1.0 mm(mean ± s.e.m.). For a female wild-type Drosophila, a jump of 30 mm corresponds to a kinetic energy of 200 nJ on take-off (allowing 20% of the energy to overcome air resistance). We develop equations of motion for a linear force–time model of take-off and calculate that the time to take-off is 5.0 ms and the peak force should be 274 μN (137 μN leg–1).

We predicted, from the role of octopamine in enhancing muscle tension in several locust muscles, that if stored elastic energy plays no part in force development, then genetic manipulation of the octopaminergic system would directly affect force production and jumping in Drosophila. Using two mutants deficient in the octopaminergic system, TbhnM18(M18) and TyrRhono (hono), we found significantly reduced jumping distances (20.7±0.7 and 20.7±0.4 mm, respectively) and force production (52% and 55%, respectively) compared with wild type.

From the reduced distance and force production in M18, a mutant deficient in octopamine synthesis, and in hono, a tyramine/octopamine receptor mutant, we conclude that in Drosophila, as in locusts,octopamine modulates escape jumping. We conclude that the fly does not need to store large quantities of elastic energy in order to make its jump because (1)the measured and calculated forces agree to within 40% and (2) the reduction in distances jumped by the mutants correlates well with their reduction in measured peak force.
Models of hydrodynamic flow in the bowhead whale filter feeding apparatus
Authors: Werth Alexander J.
Published: August 2004

Anatomical and behavioral analyses suggest that the filtration mechanism of bowhead and right whales (Balaenidae) is driven by hydrodynamic as well as ram hydraulic pressures. Complementary models were devised to investigate biomechanical aspects of water flow in the buccal cavity of the bowhead whale Balaena mysticetus during continuous filter feeding. A mathematical model was created to test and quantify water flow predictions with steady state hydromechanical equations; a physical model of the bowhead mouth(approximately 1/15 scale) was constructed to visualize flow processes. Both models rely on morphometric data obtained from whales harvested by Inupiat Eskimos for subsistence purposes along with information on foraging ecology(locomotor velocity, gape, etc.). Results indicate that unique features of balaenid oral construction and function (e.g. subrostral gap, orolabial sulcus, curvature of baleen, extensive mandibular rotation and lingual mobility) not only permit steady, unidirectional flow of water through the mouth, but also establish Bernoulli and Venturi effects during feeding. These hydrodynamic conditions allow balaenids to improve filtering efficiency and avoid creation of an anterior compressive wave (by increasing flow velocity and thereby reducing pressure) so that they may capture elusive prey even at slow swimming speeds.
Ionic interactions between PRNA and P protein in Bacillus subtilis RNase P characterized using a magnetocapture-based assay
Authors: DAY-STORMS JEREMY J. , NIRANJANAKUMARI S. , FIERKE CAROL A.
Published: August 2004

Ribonuclease P (RNase P) is a ribonucleoprotein complex that catalyzes the cleavage of the 5′ end of precursor tRNA. To characterize the interface between the Bacillus subtilis RNA (PRNA) and protein (P protein) components, the intraholoenzyme KD is determined as a function of ionic strength using a magnetocapture-based assay. Three distinct phases are evident. At low ionic strength, the affinity of PRNA for P protein is enhanced as the ionic strength increases mainly due to stabilization of the PRNA structure by cations. Lithium substitution in lieu of potassium enhances the affinity at low ionic strength, whereas the addition of ATP, known to stabilize the structure of P protein, does not affect the affinity. At high ionic strength, the observed affinity decreases as the ionic strength increases, consistent with disruption of ionic interactions. These data indicate that three to four ions are released on formation of holoenzyme, reflecting the number of ion pairs that occur between the P protein and PRNA. At moderate ionic strength, the two effects balance so that the apparent KD is not dependent on the ionic strength. The KD between the catalytic domain (C domain) and P protein has a similar triphasic dependence on ionic strength. Furthermore, the intraholoenzyme KD is identical to or tighter than that of full-length PRNA, demonstrating that the P protein binds solely to the C domain. Finally, pre-tRNAasp (but not tRNAasp) stabilizes the PRNA•P protein complex, as predicted by the direct interaction between the P protein and pre-tRNA leader.
Photolabile anticodon stem–loop analogs of tRNAPhe as probes of ribosomal structure and structural fluctuation at the decoding center
Authors: DRUZINA ZHANNA , COOPERMAN BARRY S.
Published: August 2004

With the recent availability of high-resolution structures of bacterial ribosomes, studies of ribosome-catalyzed protein biosynthesis are now focusing on the nature of conformational changes that occur as the ribosome exerts its complex catalytic function. Photocrosslinking can be relevant for this purpose by providing clues to ribosomal structural fluctuations and dynamics. Here we describe crosslinking experiments on 70S ribosomes using two photolabile anticodon stem–loop derivatives of Escherichia coli tRNAPhe carrying a 4-thiouridine in either position 33 or 37 and denoted Ph-ASLs. One or both of these Ph-ASLs bind to the tRNA A-, P-, and E-sites on the ribosome, with both binding to and photocrosslinking from the E-site showing strong dependence on the presence of a tRNA in the P-site. Both Ph-ASLs crosslink to the extreme 3′-end of 16S rRNA from both the P- and E-sites, providing direct confirmatory evidence in solution for the folding back of the 3′-end toward the decoding region. This suggests that the 3′-end of 16S rRNA may act as a switch in controlling mRNA access to the decoding center, a phenomenon of potential relevance for the translation of leaderless mRNA. E-site bound Ph-ASLs also form photocrosslinks to nucleotides 1395–1398, 1399–1400, and 1491–1494 at the top of helix 44 of 16S rRNA, indicating movement of the decoding center from a position between the A- and P-sites seen in the crystal structure to one neighboring the E-site.
In search of RNase P RNA from microbial genomes
Authors: LI YONG , ALTMAN SIDNEY
Published: August 2004

A simple procedure has been developed to quickly retrieve and validate the DNA sequence encoding the RNA subunit of ribonuclease P (RNase P RNA) from microbial genomes. RNase P RNA sequences were identified from 94% of bacterial and archaeal complete genomes where previously no RNase P RNA was annotated. A sequence was found in camelpox virus, highly conserved in all orthopoxviruses (including smallpox virus), which could fold into a putative RNase P RNA in terms of conserved primary features and secondary structure. New structure features of RNase P RNA that enable one to distinguish bacteria from archaea and eukarya were found. This RNA is yet another RNA that can be a molecular criterion to divide the living world into three domains (bacteria, archaea, and eukarya). The catalytic center of this RNA, and its detection from some environmental whole genome shotgun sequences, is also discussed.
Numerical study of scalar mixing in curved channels at low Reynolds numbers
Authors: Vanka S. P. , Luo G. , Winkler C. M.
Published: August 2004

A computational study has been performed to determine the rates of mixing in a curved square duct at low Reynolds numbers of interest to microfluidic applications. Two flow streams with inlet scalar concentrations of zero and unity in the two halves of a duct perpendicular to the plane of curvature were allowed to mix by convection and diffusion. Concentration distributions and unmixedness coefficients are presented for several Reynolds and Schmidt numbers and are compared with values for a straight channel of equivalent length. It is seen that for large Schmidt number fluids, mixing is considerably enhanced at moderately low Reynolds numbers (Re ∼ 10), but is not enhanced at Reynolds numbers of the order of 0.1. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2359–2368, 2004
Effect of waveforms on morphology development in chaotic mixing of polymers
Authors: Sau Madhusudan , Jana Sadhan C.
Published: August 2004

The effect of waveforms of rotor motion in a chaotic mixing device on the development of morphology in the blending of polypropylene (PP) and polyamide 6 (PA6) was investigated. The rotor motion was delivered in a steady and time‐periodic manner and the mixing effectiveness was evaluated in terms of Poincaré maps and stretching distribution, the speed of conversion of PP‐phase into droplets, and droplet size distribution. The pathway of morphology development, such as deformation of the PP‐phase into lamella, fibrils, and droplets, was found not to depend on the nature of the waveform. However, the makeup of each morphological form depended strongly on the particular waveform used. The best results were obtained when the rotor motion was delivered using a sine waveform. In this case, the PP‐phase turned most rapidly into fibrils and droplets and the droplets were of more uniform size. The square waveform, although produced higher mean stretching and showed more uniform mixing in Poincaré maps, yielded large‐size droplets, purportedly through premature breakup of the fibrils in the zones of weak flow, such as in the vicinity of the stationary rotors. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2346–2358, 2004
The gene responsible for PARK6 Parkinson's disease, PINK1, does not influence common forms of parkinsonism
Authors: Healy Daniel G. , Abou‐Sleiman Patrick M. , Ahmadi Kourosh R. , Muqit Miratul M. K. , Bhatia Kailash P. , Quinn Niall P. , Lees Andrew J. , Latchmann David S. , Goldstein David B. , Wood Nicholas W.
Published: August 2004

Mutations in the PINK1 gene (PARK6), a putative serine‐threonine kinase, cause autosomal recessive Parkinson's disease. PINK1 functions as a protein kinase and confers protective effects in the mitochondria, where it is primarily located. We assessed in a population of European ancestry whether common genetic variation in this novel gene influences nonmendelian forms of Parkinson's disease. We defined the linkage disequilibrium structure of PINK1 and used this to identify a set of tagging single nucleotide polymorphisms that we estimate will efficiently represent all of the common DNA variation in the entire gene. Genotyping these tags in a set of 576 Parkinson's disease patients and 514 controls did not demonstrate a case–control partition for allele or for haplotype and thus provides evidence against the existence of a common functional variants in PINK1 that has a strong influence on PD risk. Ann Neurol 2004;56:329–335
Preparation and rheological behaviors of 6‐carboxy‐chitosan
Authors: Zhou Yongguo , Yang Yuedong , Chuo Huimin , Liu Xiaomin
Published: August 2004

The hydroxymethyl groups of 2‐amino‐2‐deoxy‐D‐glucose units in chitosan were selectively oxidized to carboxyl groups with NO2 gas to form 6‐carboxy‐chitosan in aqueous 0.5 mol/L acetic acid. In optimal conditions, the 52.5% hydroxymethyl groups in chitosan could be converted into carboxyl groups. When the pH value of the solution is lower than 4.0 or more than 5.4, 6‐carboxy‐chitosan has common characteristics of a polycation or polyanion electrolyte, respectively, and when the pH value of the solution is 4.0—5.4, 6‐carboxy‐chitosan has common characteristics of an amphoteric polyelectrolyte. 6‐Carboxy‐chitosan has same macromolecular backbones as chitosan, and its isoelectric point (pI) value is 4.9. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1126–1130, 2004
Diffusion behavior of reducing agents into keratin fibers using microspectrophotometry
Authors: Kuzuhara A. , Hori T.
Published: August 2004

To investigate the penetration of thioglycolic acid (TG), thiolactic acid (TL), and L‐cysteine (CYS), into keratin fibers, cross‐sectional samples of virgin white human hair treated with TG, TL, and CYS were prepared. A new method for analyzing the diffusion behavior of reducing agents into human hair was developed. The diffusion pattern of reducing agents into human hair, which cannot be determined by optical microscopy, can be determined by the method developed. The method involves treating virgin hair fibers with TG, TL, and CYS. After the treatment, the cross‐sectioned hair samples were dyed with methylene blue and the cross‐sectional intensity scans were measured at a wavelength of 664 nm (λmax of methylene blue) with a microspectrophotometer. The three different diffusion patterns from the three reducing agents were obtained. The penetration of TG and TL into virgin human hair clearly increased by increasing the treatment time and pH. On the other hand, the penetration of CYS was less than TG and TL (CYS could not penetrate into the cortex region of the virgin human hair). Also, the diffusion pattern of TG showed Fickian type characteristics. The apparent diffusion coefficient of TG into human hair at pH 9.0 determined from the TG concentration profile was found to be 10−9 cm2/s. On the other hand, the apparent diffusion coefficient of TG into human hair at pH 7.0 was 10−10 cm2/s, and thus, the apparent diffusion coefficient of TG depended on the pH of the TG solution. From these experiments, we have concluded that the diffusion patterns of the three reducing agents in this study depended on the electrostatic interaction between the human hair and the reducing agents. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1131–1138, 2004
Sorption, diffusion, and swelling characteristics of sodium alginate and its blend membranes with poly(vinyl alcohol) in water–acetic acid mixtures
Authors: Aminabhavi Tejraj M. , Shetty Lakshmi C. , Naidu B. Vijaya Kumar , Mallikarjuna Nadagouda N. , Hanchinal Vanajakshi M.
Published: August 2004

Sorption, diffusion, and swelling characteristics of sodium alginate and its blend membranes with poly(vinyl alcohol) were investigated for water–acetic acid mixtures by using a gravimetric method at 30, 40, and 50°C. The membranes were characterized by X‐ray diffraction and Fourier transform infrared techniques. Concentration‐independent diffusion coefficients were obtained by applying Fick's relationship before completion of equilibrium sorption. Permeation coefficients were calculated from sorption and diffusion coefficients. Concentration profiles of liquids were computed considering the sheet geometry for the membrane by solving Fick's equation under suitable boundary conditions. Arrhenius activation parameters were computed for the transport processes. Experimental results and calculated quantities were discussed to understand membrane–solvent interactions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1139–1150, 2004