bluuebunny/crossref_metadata_2025 huggingface dataset:
Forensic psychiatric assessment in European Union member states
Authors: Dressing H. , Salize H. J.
Published: March 2006

Objective:  To provide a structured description and cross‐boundary comparison of legal frameworks and training standards relevant for forensic psychiatric assessment in European Union member states before the extension in May 2004.

Method:  Information on legislation and practice concerning the assessment of mentally disordered offenders was gathered by means of a detailed, structured questionnaire which was filled in by national experts.

Results:  Legal frameworks for the assessment and reassessment of mentally disordered offenders and professional training standards in forensic psychiatry vary markedly across EU member states.

Conclusion:  Currently a cross‐boundary harmonization of legal concepts appears hard to achieve. At least a formal construction and implementation of specialist training standards in forensic psychiatry would appear desirable.
Randomized controlled trial of a cannabis‐focused intervention for young people with first‐episode psychosis
Authors: Edwards J. , Elkins K. , Hinton M. , Harrigan S. M. , Donovan K. , Athanasopoulos O. , McGorry P. D.
Published: March 2006

Objective:  To evaluate a cannabis‐focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first‐episode psychosis (FEP).

Method:  Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single‐blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24).

Results:  There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post‐intervention. There were no significant group differences on psychopathology and functional ratings at follow‐up. A significant reduction in cannabis use was observed for both groups over time.

Conclusion:  PE and specific cannabis‐focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.
Polymorphic light eruption may be associated with cigarette smoking and alcohol consumption
Authors: Mentens Greet , Lambert Julien , Nijsten Tamar
Published: March 2006

Background: Although the genetic influence on polymorphic light eruption (PLE) is well established, the role of lifestyle factors is less well defined.

Methods: A retrospective case–control study was conducted that included 74 PLE patients and 102 controls. Each participant was interviewed about demographic, disease and lifestyle characteristics such as smoking, alcohol consumption and use of medications. Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).

Results: Compared with the controls, patients with PLE were significantly more likely to be younger females (P<0.05). Univariate analysis did not show a significant association between any of the smoking‐related questions and PLE. However, after adjusting for gender and drinking alcohol, patients with PLE were significantly more likely to smoke 15 cigarettes or more daily [adjusted OR=4.06 (95% CI=1.19, 13.80) compared with 0 daily cigarettes] than controls. Participants who consumed six or more drinks a week were less likely to have PLE [adjusted OR=0.24 (95% CI=0.07, 0.80)]. In contrast, women who used oral anticonceptives for a longer period were four‐fold more likely to have PLE [adjusted OR=4.74 (95% CI=1.33, 16.86)].

Conclusion: Several lifestyle factors may be associated with PLE, but further studies are warranted to confirm these retrospective findings.
Reduction of the UV burden to indoor tanners through new exposure schedules: a pilot study
Authors: Miller Sharon A. , Coelho Sergio G. , Zmudzka Barbara Z. , Beer Janusz Z.
Published: March 2006

Background: The development of new pigmentation (tan) in human skin after UV exposure requires several days. Once it is developed, the tan can last for weeks. Current recommendations for tanning exposure schedules in the USA (FDA Letter to Manufacturers: Policy on maximum timer interval and exposure schedule for sunlamps, August 21, 1986) allow exposures three times per week for the development of a tan, and one to two times per week for maintenance exposures. However, this policy is often interpreted in the indoor tanning industry as allowing three exposures per week on a continuous basis. We believe that the reduction of the recommended cumulative dose to indoor tanners should be explored. Two approaches for achieving this are (1) decreasing the number of exposures and (2) increasing the time interval between exposures. To explore such changes, we conducted a pilot study.

Methods: The pilot study involved three exposure schedules (evaluated on each of six subjects) that evolved throughout the course of the study. Digital photography, visual assessment and diffuse reflectance spectrometry were used to assess skin color changes. The six pilot subjects were studied for 8–18 weeks. The changes in skin color obtained through the use of the different exposure schedules were compared with changes reported by Caswell (Caswell M, The kinetics of the tanning response to tanning bed exposures, Photodermatol Photoimmunol Photomed 2000: 16: 10–14) who used schedules based on current recommendations.

Results: Two out of the three experimental schedules produced tans comparable with those reported by Caswell. In these two schedules, cumulative doses were a factor of 2–3 below doses from current schedules.

Conclusion: The UV burden to indoor tanners can be substantially reduced without compromising the cosmetic effect. These results need to be confirmed in a larger study.
Photolocalized purpura during ciprofloxacin therapy
Authors: Urbina Francisco , Barrios Moema , Sudy Emilio
Published: March 2006

Photosensitivity reactions reported with ciprofloxacin mimic those of sunburn, with erythema and edema in the milder forms, and painful blistering with subsequent peeling when severe. Purpuric eruptions during treatment with ciprofloxacin have been rarely reported. We describe a 30‐year‐old man who was given a 15‐day course with ciprofloxacin 500 mg twice a day for a prostatitis. Coinciding with sun exposure, he developed a purpuric, pruriginous eruption on his lower extremities, consisting of erythematous, petechial lesions located on the anterior aspect of his thighs and legs, clearly delimited by his bathing suit. The lesions cleared completely after the discontinuation of the drug and treatment with topical clobetasol. The acute reaction observed in our patient differed from a classical sunburn, consisting of confluent petechias, strictly limited to sunlight‐exposed areas, and accompanied by pruritus. Photoexposed purpuric eruptions should be considered as another side effect of ciprofloxacin therapy in addition to phosensitivity rashes.
A Multigene Family Encoding R‐SNAREs in the Ciliate Paramecium tetraurelia
Authors: Schilde Christina , Wassmer Thomas , Mansfeld Joerg , Plattner Helmut , KissmehI Roland
Published: March 2006

SNARE proteins (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) mediate membrane interactions and are conventionally divided into Q‐SNAREs and R‐SNAREs according to the possession of a glutamine or arginine residue at the core of their SNARE domain. Here, we describe a set of R‐SNAREs from the ciliate Paramecium tetraurelia consisting of seven families encoded by 12 genes that are expressed simultaneously. The complexity of the endomembrane system in Paramecium can explain this high number of genes. All P. tetraurelia synaptobrevins (PtSybs) possess a SNARE domain and show homology to the Longin family of R‐SNAREs such as Ykt6, Sec22 and tetanus toxin‐insensitive VAMP (TI‐VAMP). We localized four exemplary PtSyb subfamilies with GFP constructs and antibodies on the light and electron microscopic level. PtSyb1‐1, PtSyb1‐2 and PtSyb3‐1 were found in the endoplasmic reticulum, whereas PtSyb2 is localized exclusively in the contractile vacuole complex. PtSyb6 was found cytosolic but also resides in regularly arranged structures at the cell cortex (parasomal sacs), the cytoproct and oral apparatus, probably representing endocytotic compartments. With gene silencing, we showed that the R‐SNARE of the contractile vacuole complex, PtSyb2, functions to maintain structural integrity as well as functionality of the osmoregulatory system but also affects cell division.
A critical analysis of UK public health policies in relation to diet and nutrition in low‐income households
Authors: Attree Pamela
Published: March 2006

Diet and nutrition, particularly among low‐income groups, is a key public health concern in the UK. Low levels of fruit and vegetable consumption, and obesity, especially among children, have potentially severe consequences for the future health of the nation. From a public health perspective, the UK government's role is to help poorer families make informed choices within healthy frameworks for living. However, the question is – to what extent are such policies in accordance with lay experiences of managing diet and nutrition on a low‐income? This paper critically examines contemporary public health policies aimed at improving diet and nutrition, identifying the underlying theories about the influences on healthy eating in poor families, and exploring the extent to which these assumptions are based on experiential accounts. It draws on two qualitative systematic reviews – one prioritizing low‐income mothers’ accounts of ‘managing’ in poverty; and the other focusing on children's perspectives. The paper finds some common ground between policies and lay experiences, but also key divergencies. Arguably, the emphasis of public health policy on individual behaviour, coupled with an ethos of empowered consumerism, underplays material limitations on ‘healthy eating’ for low‐income mothers and children. Health policies fail to take into account the full impact of structural influences on food choices, or recognize the social and emotional factors that influence diet and nutrition. In conclusion, it is argued that while health promotion campaigns to improve low‐income families’ diets do have advantages, these are insufficient to outweigh the negative effects of poverty on nutrition.
Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B
Authors: Wieczerzak E. , Jankowska E. , Rodziewicz‐Motowidło S. , Giełdoń A. , Łągiewka J. , Grzonka Z. , Abrahamson M. , Grubb A. , Brömme D.
Published: March 2006

Abstract:  We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, Ki, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe (7) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7. We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.
Thiophilic interaction chromatography of Alzheimer's β‐amyloid peptides
Authors: Parry S. , Todorova‐Balvay D. , Srikrishnan T. , Sulkowski E.
Published: March 2006

Abstract:  Alzheimer's disease is characterized by a progressive formation of senile plaques in the brain, the major constituent of which is β‐amyloid (Aβ) peptide, a proteolytic product of the transmembrane β‐amyloid precursor protein (APP). Prior to the measurement of levels of the Aβ peptide for diagnostic purposes, this peptide must be isolated from the myriad of proteins resident in the human serum. Thiophilic interaction chromatography is an effective method for the isolation of proteins and peptides containing clusters of aromatic residues such as tryptophan, phenylalanine and tyrosine. The purpose of the present study was to develop a protocol for binding and recovery of Aβ peptides (1–38), (1–40) and (1–42) to T‐gels by varying T‐gel type and elution conditions such as the salt concentration and type of eluent. We established the minimal salt concentration necessary for the binding of the Aβ(1–40) peptide to the 3S‐gel; binding at that concentration was subsequently compared with that of model proteins, lysozyme and α‐chymotrypsin and this methodology was extended to 2S‐gels and PyS. β‐Amyloid peptide (1–40) showed a remarkably strong affinity for all three types of T‐gels in comparison to lysozyme and α‐chymotrypsin and was found to bind best to 2S‐gel.
Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V2 vasopressin agonists
Authors: Sikorska (née Trzepałka) E. , Ślusarz R. , Lammek B.
Published: March 2006

Abstract:  Conformational studies of three agonists of V2 receptor modified with 1‐aminocyclohexane‐1‐carboxylic acid (Acc), [Acc2,DArg8]VP, [Acc3]AVP and [Cpa1,Acc3]AVP, using 2D NMR and theoretical calculations are presented in this paper. It is believed that α,α‐disubstituted amino acids, such as Acc, affect the formation of either 310 or α‐helical conformation. Moreover, a peptide with Acc may adopt either the γ‐ or an inverse γ‐turn over it. Thus, incorporation of Acc into the arginine‐vasopressin sequence induced C7‐membered ring conformation with Acc at the top of it, and additional formation of β‐bend involving residues in the 2–5 fragment of the peptides. Furthermore, the analogues are also characterized by type I of β‐turn involving residues Acc3‐Cys6 in [Acc3]AVP and [Cpa1,Acc3]AVP, and by type IV or II′ in [Acc2,DArg8]VP. Replacement of Tyr at position 2 of [Acc2,DArg8]VP with Acc afforded a hydrogen bond between the guanidine moiety of DArg8 and the side chain of either Asn5 or Gln4. In the remaining analogues, the β‐turn comprising the Cys6‐Gly9 residues allows the positively charged side chain of Arg8 to be directed toward Tyr2. The substitution of Cys1 with Cpa1 enhances hydrophobic properties of N‐terminal part of the molecule strengthening thereby the affinity to the binding pocket of receptors.
HIV‐1 integrase inhibition by pyrrole/imidazole‐containing polyamides
Authors: Zakharova O.D. , Baranova S. , Parissi V. , Ryabinin V.A. , Sinyakov A.N. , Litvak S. , Litvak L.T. , Nevinsky G.A.
Published: March 2006

Abstract:  Since HIV‐1 integrase (IN) is responsible for catalyzing the insertion of the viral genome into the host cell chromosome, it provides an attractive target for antiviral drug design. We synthesized a set of pyrrole/imidazole‐containing polyamides (PAs), specifically interacting within the minor groove of DNA in order to find inhibitors of integrase. All PAs contained different N‐ and C‐terminal groups. A first family of polyamides, the (a) series, contained 3 or 4 heterocyclic rings (pyrrole or imidazole) linearly bound. A second family, the (b) series are ‘bifunctional PAs’ that contained two linear chains of oligocarboxamides in opposite orientation, each with 3 or 4 pyrrole or imidazole units connected with a flexible spacer. The inhibition of integrase activity by the (a) series depended on their sequence and increased with the number of rings, especially imidazole residues. Bifunctional compounds were tripyrroles with different spacers, or different combinations of pyrroles and imidazoles keeping the same spacer. The affinity of integrase for bifunctional tripyrroles linked by three different spacers (γ‐aminobutyric acid, β‐alanine or glycine) strongly depended on the spacer. Changing from γ‐aminobutyric acid to shorter spacers increased the affinity. The other group of bifunctional PAs containing alternating imidazoles or pyrrole rings, but with the same spacer, showed affinities that depended on the sequence of unnatural amino acids. These data indicate that some of the newly synthesized PAs can provide a rationale for the design of drugs targeting the integration step.
GnRH analogues containing conformationally restricted amino acids in positions 3 and 6: differential impact on pituitary binding affinity and direct antiproliferative effect on breast cancer cells†
Authors: Zompra A.A. , Magafa V. , Lamari F.N. , Nikolopoulou A. , Nock B. , Maina T. , Spyroulias G.A. , Karamanos N.K. , Cordopatis P.
Published: March 2006

Abstract: Analogues of GnRH have been widely used in oncology and gynaecology to induce reversible chemical castration. In addition to the classic hypophysiotropic action of GnRH, it has been shown that many malignant cells, such as breast cancer cells, secrete GnRH and express the GnRH receptor/s. In order to study the effect of modifications in position3and6of GnRH on both pituitary binding affinity and breast cancer cell proliferation, we synthesized eight new GnRH analogues. All GnRH analogues lacked the carboxy–terminal Gly10–amide of GnRH and an ethylamide residue was added to Pro9. Gly6was substituted by α,α‐dialkyl amino acids (Aib:α‐aminoisobutyric acid, Deg: diethylglycine) and Trp3by D–Trp, D‐ and L‐1,2,3,4,‐tetrahydro‐isoquinoline‐3‐carboxylic acid (Tic). During competition binding experiments in mouse anterior pituitaryαT3‐1 cells, [Aib6,desGly10]GnRH‐NHEt bound to the GnRH receptor with IC50values comparable to those of parent hormone in contrast to the analogues substituted at position3. However, [L‐Tic3,Deg6,desGly10]GnRH‐NHEt had high pituitary binding affinity. With the exception of GnRH and [Aib6,desGly10]GnRH‐NHEt, all GnRH analogues significantly inhibited the proliferation of human breast cancer cells (MCF‐7); higher inhibitory effect was observed for analogues modified at position3. Results show differential impact of the modifications on the binding affinity to the GnRH receptor in mouse pituitary cells and on the inhibition of human breast cancer cell proliferation and provide insight into structure‐activity relationship of GnRH in different biological systems.
Band-Limited Trajectory Planning and Tracking for Certain Dynamically Stabilized Mobile Systems
Authors: Pathak Kaustubh , Agrawal Sunil K.
Published: March 2006

In this paper, a general framework for trajectory planning and tracking is formulated for dynamically stabilized mobile systems, e.g., inverted wheeled pendulums and autonomous helicopters. Within this framework, the system state is divided into slow and fast substates. The fast substate is used as a pseudocontrol for tracking a desired slow substate trajectory. First, an exponential fast substate controller is designed to track a fast substate reference trajectory. This fast substate reference trajectory is, in turn, planned so that the slow substate follows its desired trajectory. To ensure that the fast substate reference trajectory is feasible for the exponential controller, it is designed using band-limited “Sinc” functions whose maximum frequency is less than the inverse of the time constant of the exponential controller. To illustrate the procedure, the dynamic model of an inverted wheeled pendulum is reformulated by a partial feedback linearization such that it is amenable to the separation into slow and fast components. The planning and tracking controller design is explained using simulation results. This technique is shown to be easily embedded inside a modified nonlinear model predictive control framework for the slow subsystem. This framework tries to explicitly take the computational delay into account. The computation time required for this technique is encouraging from a real-world implementation perspective.
Shared Control in Haptic Systems for Performance Enhancement and Training
Authors: O’Malley Marcia K. , Gupta Abhishek , Gen Matthew , Li Yanfang
Published: March 2006

This paper presents a shared-control interaction paradigm for haptic interface systems, with experimental data from two user studies. Shared control, evolved from its initial telerobotics applications, is adapted as a form of haptic assistance in that the haptic device contributes to execution of a dynamic manual target-hitting task via force commands from an automatic controller. Compared to haptic virtual environments, which merely display the physics of the virtual system, or to passive methods of haptic assistance for performance enhancement based on virtual fixtures, the shared-control approach offers a method for actively demonstrating desired motions during virtual environment interactions. The paper presents a thorough review of the literature related to haptic assistance. In addition, two experiments were conducted to independently verify the efficacy of the shared-control approach for performance enhancement and improved training effectiveness of the task. In the first experiment, shared control is found to be as effective as virtual fixtures for performance enhancement, with both methods resulting in significantly better performance in terms of time between target hits for the manual target-hitting task than sessions where subjects feel only the forces arising from the mass-spring-damper system dynamics. Since shared control is more general than virtual fixtures, this approach may be extremely beneficial for performance enhancement in virtual environments. In terms of training enhancement, shared control and virtual fixtures were no better than practice in an unassisted mode. For manual control tasks, such as the one described in this paper, shared control is beneficial for performance enhancement, but may not be viable for enhancing training effectiveness.
Internet-Based Bilateral Teleoperation Based on Wave Variable With Adaptive Predictor and Direct Drift Control
Authors: Ching Ho , Book Wayne J.
Published: March 2006

In a conventional bilateral teleoperation, transmission delay over the Internet can potentially cause instability. A wave variable algorithm guarantees teleoperation stability under varying transmission delay at the cost of poor transient performance. Adding a predictor on the master side can reduce this undesirable side effect, but that would require a slave model. An inaccurate slave model used in the predictor as well as variations in transmission delay, both of which are likely under realistic situations, can result in steady-state errors. A direct drift control algorithm is used to drive this error to zero, regardless of the source of the error. A semi-adaptive predictor that can distinguish between free space and a rigid contact environment is used to provide a more accurate force feedback on the master side. A full adaptive predictor is also used that estimates the environmental force using recursive least squares with a forgetting factor. This research presents the experimental results and evaluations of the previously mentioned wave-variable-based methods under a realistic operation environment using a real master and slave. The algorithm proposed is innovative in that it takes advantage of the strengths of several control methods to build a promising bilateral teleoperation setup that can function under varying transmission delay, modeling error, and changing environment. Success could lead to practical applications in various fields, such as space-based remote control, and telesurgery.
Dynamics, Design and Simulation of a Novel Microrobotic Platform Employing Vibration Microactuators
Authors: Vartholomeos Panagiotis , Papadopoulos Evangelos
Published: March 2006

This paper presents the analysis, design, and simulation of a novel microrobotic platform that is able to perform translational and rotational sliding with submicrometer positioning accuracy and develop velocities up to 1.5mm∕s. The platform actuation system is novel and based on centripetal forces generated by vibration micromotors. The motion principle is discussed in detail, and the dynamic model of the platform and of its actuation system is developed. Analytical expressions for the distinct modes of operation of the platform are derived and used to provide system design guidelines. Simulations are performed that verify the analytical results, demonstrate the platform capabilities, and examine its transient response. The microrobot design is simple, compact, and of low cost. In addition, the energy supply of the mechanism can be accomplished in an untethered mode using simple means, such as single-cell batteries.
A Unified Force Controller for a Proportional-Injector Direct-Injection Monopropellant-Powered Actuator
Authors: Fite Kevin B. , Mitchell Jason E. , Barth Eric J. , Goldfarb Michael
Published: March 2006

This paper describes the modeling and control of a proportional-injector direct-injection monopropellant-powered actuator for use in power-autonomous human-scale mobile robots. The development and use of proportional (as opposed to solenoid) injection valves enables a continuous and unified input/output description of the device, and therefore enables the development and implementation of a sliding-mode-type controller for the force control of the proposed actuator, which provides the stability guarantees characteristic of a sliding-mode control approach. Specifically, a three-input, single-output model of the actuation system behavior is developed, which takes a nonlinear non-control-canonical form. In order to implement a nonlinear controller, a constraint structure is developed that effectively renders the system single input, single output, and control canonical, and, thus, of appropriate form for the implementation of a sliding-mode controller. A sliding-mode controller is then developed and experimentally implemented on the proposed actuator. Experimental results demonstrate closed-loop force tracking with a saturation-limited bandwidth of approximately 6Hz.
Equilibrium Point Control of a 2-DOF Manipulator
Authors: Clapa Damien J. , Croft Elizabeth A. , Hodgson Antony J.
Published: March 2006

Programmable mechanical compliance in actuation is desirable for human interaction tasks and important for producing biomimetic motion, particularly for robots designed for use in domestic settings. In this paper, the equilibrium point (EP) hypothesis is proposed and implemented as a new strategy for controlling programmable compliance. The primary objective of this work is to design and demonstrate a simple robot control strategy that can potentially be used by assistive robots to learn and execute compliant interaction tasks from human demonstrations. A 2-DOF planar manipulator activated by McKibben actuators was constructed for the purpose of demonstrating the application of the EP hypothesis on an inexpensive robotic platform, such as might be used in domestic applications. The equilibrium angle and stiffness of each of the joints on the manipulator can be independently programmed. The results presented herein show stable and satisfactory tracking behavior during free motion, interaction, and transition tasks for a robot control system inspired by the EP hypothesis and implemented with a linear proportional-integral (PI) control strategy.
Design of Machines With Compliant Bodies for Biomimetic Locomotion in Liquid Environments
Authors: Valdivia y Alvarado Pablo , Youcef-Toumi Kamal
Published: March 2006

The aim of this work is to investigate alternative designs for machines intended for biomimetic locomotion in liquid environments. For this, structural compliance instead of discrete assemblies is used to achieve desired mechanism kinematics. We propose two models that describe the dynamics of special compliant mechanisms that can be used to achieve biomimetic locomotion in liquid environments. In addition, we describe the use of analytical solutions for mechanism design. Prototypes that implement the proposed compliant mechanisms are presented and their performance is measured by comparing their kinematic behavior and ultimate locomotion performance with the ones of real fish. This study shows that simpler, more robust mechanisms, as the ones described in this paper, can display comparable performance to existing designs.
The Effect of Leg Specialization in a Biomimetic Hexapedal Running Robot
Authors: Clark Jonathan E. , Cutkosky Mark R.
Published: March 2006

The biologically inspired Sprawl family of hexapedal robots has shown that fast and stable running is possible with only open-loop control. Proper design of the passively self-stabilizing leg structure has enabled these robots to run at speeds of up to 15 bodylengths/s and over uneven terrain. Unlike other running robots built to date, the Sprawl robots’ front and rear legs are designed to preform distinct functional roles. Like the cockroaches that inspired them, the front legs of the robots act to lift and decelerate, while the rear legs provide the primary forward thrust. This paper uses a dynamic simulation to investigate the effect that changing the robot’s leg structure and posture has on its performance. The simulation results support our hypothesis that the use of a differential leg function induced through postural adjustments effectively trades efficiency for stability.
Visual and Tactile-Based Terrain Analysis Using a Cylindrical Mobile Robot
Authors: Reina Giulio , Foglia Mario M. , Milella Annalisa , Gentile Angelo
Published: March 2006

Ground autonomous mobile robots have important applications, such as reconnaissance, patrol, planetary exploration, and military applications. In order to accomplish tasks on rough terrain, control and planning methods must consider the physical characteristics of the vehicle and of its environment. Failure to understand these characteristics could lead to vehicle endangement and consequent mission failure. This paper describes recent and current work at the Politecnico of Bari in collaboration with the University of Lecce in the area of deformable terrain mobility and sensing. A cylindrical mobile robot is presented and its rolling motion on terrain is studied from a theoretical and experimental prospect. A comprehensive model is developed taking into account the interaction of the vehicle with the terrain and the related dynamic ill effects, such as rolling resistance and slip, and it is experimentally validated. An unconventional application of the vehicle serving as a tactile sensor is discussed and experimental results are presented showing the effectiveness of the cylindrical mobile robot in estimating the properties of homogeneous, deformable terrain, which in turn can be used to assess the vehicle traversability.
Model-Based Cancellation of Biodynamic Feedthrough Using a Force-Reflecting Joystick
Authors: Gillespie R. Brent , Sövényi Szabolcs
Published: March 2006

Manual control performance on-board a moving vehicle is often impeded by biodynamic feedthrough—the effects of vehicle motion feeding through the operator’s body to produce unintended forces on the control interface. In this paper, we propose and experimentally test a model-based controller that acts through a motorized manual interface to cancel the effects of biodynamic feedthrough. The cancellation controller is based on characterization data collected using an accelerometer on the vehicle and a force sensor embedded in the manual interface and a protocol under which the manual interface is temporarily immobilized while in the grip of the operator. The biodynamic model fit to the data is based in turn on a carefully constructed model of the coupled vehicle-operator system. The impact of biodynamic feedthrough and the ability of the model-based controller to cancel its effects were estimated through an experiment in which 12 human subjects used a joystick to carry out a pursuit tracking task on-board a single-axis motion platform. Cancellation controllers derived from biodynamic models fit individually to each subject significantly improved pursuit tracking performance, as evidenced by a 27% reduction in root-mean-square tracking error, a 32% improvement in time-on-target, and an increase in crossover frequency from 0.11 to 0.15 Hz.
Design Methodology for Biomimetic Propulsion of Miniature Swimming Robots
Authors: Behkam Bahareh , Sitti Metin
Published: March 2006

Miniature and energy-efficient propulsion systems hold the key to maturing the technology of swimming microrobots. In this paper, two new methods of propulsion inspired by the motility mechanism of prokaryotic and eukaryotic microorganisms are proposed. Hydrodynamic models for each of the two methods are developed, and the optimized design parameters for each of the two propulsion modes are demonstrated. To validate the theoretical result for the prokaryotic flagellar motion, a scaled-up prototype of the robot is fabricated and tested in silicone oil, using the Buckingham PI theorem for scaling. The proposed propulsion methods are appropriate for the swimming robots that are intended to swim in low-velocity fluids.
Cell-Type-Specific Repression of Internal Ribosome Entry Site Activity by Double-Stranded RNA-Binding Protein 76
Authors: Merrill Melinda K. , Dobrikova Elena Y. , Gromeier Matthias
Published: March 2006

Translation of picornavirus plus-strand RNA genomes occurs via internal ribosomal entry at highly structured 5′ untranslated regions. In addition to canonical translation factors, translation rate is likely influenced by supplementary host and viral
trans
-acting factors. We previously reported that insertion of a heterologous human rhinovirus type 2 internal ribosomal entry site (IRES) into the poliovirus (PV) genome, generating the chimeric virus PV-RIPO, selectively abrogates viral translation and propagation in neurons, which eliminate poliovirus's signature neuropathogenicity. While severely deficient in cells of neuronal lineage, the rhinovirus IRES promotes efficient propagation of PV-RIPO in cancer cells. Tumor-specific IRES function can be therapeutically exploited to direct viral cytotoxicity to cancer cells. Neuron-glioma heterokaryon analysis implicates neuronal
trans-
dominant inhibition in this effect, suggesting that host
trans
-acting factors repress IRES function in a cell-type-specific manner. We identified a set of proteins from neuronal cells with affinity for the rhinovirus IRES, including double-stranded RNA-binding protein 76 (DRBP76). DRBP76 associates with the IRES in neuronal but not in malignant glioma cells. Moreover, DRBP76 depletion in neuronal cells enhances rhinovirus IRES-driven translation and virus propagation. Our observations suggest that cell-type-specific association of DRBP76 with the rhinovirus IRES represses PV-RIPO translation and propagation in neuronal cells.
African Swine Fever Virus pB119L Protein Is a Flavin Adenine Dinucleotide-Linked Sulfhydryl Oxidase
Authors: Rodríguez Irene , Redrejo-Rodríguez Modesto , Rodríguez Javier M. , Alejo Alí , Salas José , Salas María L.
Published: March 2006

Protein pB119L of African swine fever virus belongs to the Erv1p/Alrp family of sulfhydryl oxidases and has been described as a late nonstructural protein required for correct virus assembly. To further our knowledge of the function of protein pB119L during the virus life cycle, we have investigated whether this protein possesses sulfhydryl oxidase activity, using a purified recombinant protein. We show that the purified protein contains bound flavin adenine dinucleotide and is capable of catalyzing the formation of disulfide bonds both in a protein substrate and in the small molecule dithiothreitol, the catalytic activity being comparable to that of the Erv1p protein. Furthermore, protein pB119L contains the cysteines of its active-site motif CXXC, predominantly in an oxidized state, and forms noncovalently bound dimers in infected cells. We also show in coimmunoprecipitation experiments that protein pB119L interacts with the viral protein pA151R, which contains a CXXC motif similar to that present in thioredoxins. Protein pA151R, in turn, was found to interact with the viral structural protein pE248R, which contains disulfide bridges and belongs to a class of myristoylated proteins related to vaccinia virus L1R, one of the substrates of the redox pathway encoded by this virus. These results suggest the existence in African swine fever virus of a system for the formation of disulfide bonds constituted at least by proteins pB119L and pA151R and identify protein pE248R as a possible final substrate of this pathway.
Herpes Simplex Virus gE/gI Must Accumulate in the
trans
-Golgi Network at Early Times and Then Redistribute to Cell Junctions To Promote Cell-Cell Spread
Authors: Farnsworth Aaron , Johnson David C.
Published: March 2006

Herpes simplex virus (HSV) glycoprotein heterodimer gE/gI is necessary for virus spread in epithelial and neuronal tissues. Deletion of the relatively large gE cytoplasmic (CT) domain abrogates the ability of gE/gI to mediate HSV spread. The gE CT domain is required for the sorting of gE/gI to the
trans
-Golgi network (TGN) in early stages of virus infection, and there are several recognizable TGN sorting motifs grouped near the center of this domain. Late in HSV infection, gE/gI, other viral glycoproteins, and enveloped virions redistribute from the TGN to epithelial cell junctions, and the gE CT domain is also required for this process. Without the gE CT domain, newly enveloped virions are directed to apical surfaces instead of to cell junctions. We hypothesized that the gE CT domain promotes virus envelopment into TGN subdomains from which nascent enveloped virions are sorted to cell junctions, a process that enhances cell-to-cell spread. To characterize elements of the gE CT domain involved in intracellular trafficking and cell-to-cell spread, we constructed a panel of truncation mutants. Specifically, these mutants were used to address whether sorting to the TGN and redistribution to cell junctions are necessary, and sufficient, for gE/gI to promote cell-to-cell spread. gE-519, lacking 32 C-terminal residues, localized normally to the TGN early in infection and then trafficked to cell junctions at late times and mediated virus spread. By contrast, mutants gE-495 (lacking 56 C-terminal residues) and gE-470 (lacking 81 residues) accumulated in the TGN but did not traffic to cell junctions and did not mediate cell-to-cell spread. A fourth mutant, gE-448 (lacking most of the CT domain), did not localize to cell junctions and did not mediate virus spread. Therefore, the capacity of gE/gI to promote cell-cell spread requires early localization to the TGN, but this is not sufficient for virus spread. Additionally, gE CT sequences between residues 495 and 519, which contain no obvious cell sorting motifs, are required to promote gE/gI traffic to cell junctions and cell-to-cell spread.
Membrane-Anchored Inhibitory Peptides Capture Human Immunodeficiency Virus Type 1 gp41 Conformations That Engage the Target Membrane prior to Fusion
Authors: Melikyan Gregory B. , Egelhofer Marc , von Laer Dorothee
Published: March 2006

Soluble peptides derived from the C-terminal heptad repeat domain of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors of HIV-1 entry and gp41-induced fusion. Target membrane-anchored variants of these peptides have been shown to retain inhibitory activity. Both soluble and membrane-anchored C peptides (MACs) are thought to block fusion by binding to the N-terminal coiled coil domain of gp41 and preventing formation of the final six-helix bundle structure. However, interactions of target MACs with gp41 must be restricted to a subset of trimers that have their hydrophobic fusion peptides inserted into the target membrane. This unique feature of MACs was used to identify the intermediate step of fusion at which gp41 engaged the target membrane. Fusion between HIV envelope-expressing effector cells and target cells was measured by fluorescence microscopy. Expression of MACs in target cells led to less than twofold reduction in the extent of fusion. However, when reaction was first arrested by adding lysolipids that disfavored membrane merger, and the lipids were subsequently removed by washing, control cells supported fusion, whereas those that expressed MACs did not. The drastically improved potency of MACs implies that, at lipid-arrested stage, gp41 bridges the viral and target cell membranes and therefore more optimally binds the membrane-anchored peptides. Experimental demonstration of this intermediate shows that, similar to fusion induced by many other viral glycoproteins, engaging the target membrane by HIV-1 gp41 permits coupling between six-helix bundle formation and membrane merger.
Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region
Authors: Burns Cara Carthel , Shaw Jing , Campagnoli Ray , Jorba Jaume , Vincent Annelet , Quay Jacqueline , Kew Olen
Published: March 2006

We replaced degenerate codons for nine amino acids within the capsid region of the Sabin type 2 oral poliovirus vaccine strain with corresponding nonpreferred synonymous codons. Codon replacements were introduced into four contiguous intervals spanning 97% of the capsid region. In the capsid region of the most highly modified virus construct, the effective number of codons used (

N
C

) fell from 56.2 to 29.8, the number of CG dinucleotides rose from 97 to 302, and the G+C content increased from 48.4% to 56.4%. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased in proportion to the number of replacement codons. Plaque areas decreased over an ∼10-fold range, and virus yields decreased over an ∼65-fold range. Perhaps unexpectedly, the synthesis and processing of viral proteins appeared to be largely unaltered by the restriction in codon usage. In contrast, total yields of viral RNA in infected cells were reduced ∼3-fold and specific infectivities of purified virions (measured by particle/PFU ratios) decreased ∼18-fold in the most highly modified virus. The replicative fitness of both codon replacement viruses and unmodified viruses increased with the passage number in HeLa cells. After 25 serial passages (∼50 replication cycles), most codon replacements were retained, and the relative fitness of the modified viruses remained well below that of the unmodified virus. The increased replicative fitness of high-passage modified virus was associated with the elimination of several CG dinucleotides. Potential applications for the systematic modulation of poliovirus replicative fitness by deoptimization of codon usage are discussed.
Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills (
Mandrillus sphinx
)
Authors: Onanga Richard , Souquière Sandrine , Makuwa Maria , Mouinga-Ondeme Augustin , Simon François , Apetrei Cristian , Roques Pierre
Published: March 2006

Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4
+
and CD8
+
cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10
7
to 10
8
RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10
5
to 10
6
RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10
5
to 10
6
DNA copies/10
6
cells) and stabilized at 10
3
to 10
4
DNA copies/10
6
cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3
+
CD4
+
cells in the LNs occurred in animals with high peak VLs. CD4
+
and CD8
+
T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.
The Peptide-Binding and ATPase Domains of Recombinant hsc70 Are Required To Interact with Rotavirus and Reduce Its Infectivity
Authors: Pérez-Vargas Jimena , Romero Pedro , López Susana , Arias Carlos F.
Published: March 2006

The heat shock cognate protein hsc70 has been implicated as a postattachment cell receptor for rotaviruses. Here we show that hsc70 interacts specifically with rotaviruses through its peptide-binding domain, since a recombinant full-length hsc70 protein and its peptide-binding domain, but not its ATPase domain, bound triple-layered particles in a solid-phase assay, and known ligands of hsc70 competed this binding. The peptide ligands of hsc70 were also shown to block rotavirus infectivity when added to cells before virus infection, suggesting that hsc70 on the surface of MA104 cells also interacts with the virus through its peptide-binding domain and that this interaction is important for virus entry. When purified infectious virus was incubated with soluble hsc70 in the presence of the cochaperone hsp40 and ATP and then pelleted through a sucrose cushion, the recovered virus had lost 60% of its infectivity, even though hsc70 was not detected in the pellet fraction. The hsc70-treated virus showed slightly different reactivities with monoclonal antibodies and was more susceptible to heat and basic pHs than the untreated virus, suggesting that hsc70 induces a subtle conformational change in the virus that results in a reduction of its infectivity. The relevance of the ATPase activity of hsc70 for reducing virus infectivity was demonstrated by the finding that in the presence of a nonhydrolyzable analogue of ATP, virus infectivity was not affected, and a mutant protein lacking ATPase activity failed to reduce virus infection. Altogether, these results suggest that during cell infection, the interaction of the virus with hsc70 on the surface of MA104 cells results in a conformational change of virus particles that facilitates their entry into the cell cytoplasm.
Nonstructural Protein of Infectious Bursal Disease Virus Inhibits Apoptosis at the Early Stage of Virus Infection
Authors: Liu Meihong , Vakharia Vikram N.
Published: March 2006

Infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (NS). This protein has been implicated to play a role in the induction of apoptosis. In this study, we investigate the kinetics of viral replication during a single round of viral replication and examine the mechanism of IBDV-induced apoptosis. Our results show that it is caspase dependent and activates caspases 3 and 9. Nuclear factor kappa B (NF-κB) is also activated and is required for IBDV-induced apoptosis. The NF-κB inhibitor MG132 completely inhibited IBDV-induced DNA fragmentation, caspase 3 activation, and NF-κB activation. To study the function of the NS protein in this context, we generated the recombinant rGLS virus and an NS knockout mutant, rGLSNSΔ virus, using reverse genetics. Comparisons of the replication kinetics and markers for virally induced apoptosis indicated that the NS knockout mutant virus induces earlier and increased DNA fragmentation, caspase activity, and NF-κB activation. These results suggest that the NS protein has an antiapoptotic function at the early stage of virus infection.