ResearchPad - thumbs Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A practical 3D-printed soft robotic prosthetic hand with multi-articulating capabilities]]> Soft robotic hands with monolithic structure have shown great potential to be used as prostheses due to their advantages to yield light weight and compact designs as well as its ease of manufacture. However, existing soft prosthetic hands design were often not geared towards addressing some of the practical requirements highlighted in prosthetics research. The gap between the existing designs and the practical requirements significantly hampers the potential to transfer these designs to real-world applications. This work addressed these requirements with the consideration of the trade-off between practicality and performance. These requirements were achieved through exploiting the monolithic 3D printing of soft materials which incorporates membrane enclosed flexure joints in the finger designs, synergy-based thumb motion and cable-driven actuation system in the proposed hand prosthesis. Our systematic design (tentatively named X-Limb) achieves a weight of 253gr, three grasps types (with capability of individual finger movement), power-grip force of 21.5N, finger flexion speed of 1.3sec, a minimum grasping cycles of 45,000 (while maintaining its original functionality) and a bill of material cost of 200 USD (excluding quick disconnect wrist but without factoring in the cost reduction through mass production). A standard Activities Measure for Upper-Limb Amputees benchmark test was carried out to evaluate the capability of X-Limb in performing grasping task required for activities of daily living. The results show that all the practical design requirements are satisfied, and the proposed soft prosthetic hand is able to perform all the real-world grasping tasks of the benchmark tests, showing great potential in improving life quality of individuals with upper limb loss.

<![CDATA[Minimal force transmission between human thumb and index finger muscles under passive conditions]]>

It has been hypothesized that force can be transmitted between adjacent muscles. Intermuscle force transmission violates the assumption that muscles act in mechanical isolation, and implies that predictions from biomechanical models are in error due to mechanical interactions between muscles, but the functional relevance of intermuscle force transmission is unclear. To investigate intermuscle force transmission between human flexor pollicis longus and the index finger part of flexor digitorum profundus, we compared finger flexion force produced by passive thumb flexion after one of three conditioning protocols: passive thumb flexion-extension cycling, thumb flexion maximal voluntary contraction (MVC), and thumb extension stretch. Finger flexion force increased after all three conditions. Compared to passive thumb flexion-extension cycling, change in finger flexion force was less after thumb extension stretch (mean difference 0.028 N, 95% CI 0.005 to 0.051 N), but not after thumb flexion MVC (0.007 N, 95% CI -0.020 to 0.033 N). As muscle conditioning changed finger flexion force produced by passive thumb flexion, the change in force is likely due to intermuscle force transmission. Thus, intermuscle force transmission resulting from passive stretch of an adjacent muscle is probably small enough to be ignored.

<![CDATA[Proprioceptive measurements of perceived hand position using pointing and verbal localisation tasks]]>

Previous studies revealed that healthy individuals consistently misjudge the size and shape of their hidden hand during a localisation task. Specifically, they overestimate the width of their hand and underestimate the length of their fingers. This would also imply that the same individuals misjudge the actual location of at least some parts of their hand during the task. Therefore, the primary aim of the current study was to determine whether healthy individuals could accurately locate the actual position of their hand when hidden from view, and whether accuracy depends on the type of localisation task used, the orientation of the hidden hand, and whether the left or right hand is tested. Sixteen healthy right-handed participants performed a hand localisation task that involved both pointing to and verbally indicating the perceived position of landmarks on their hidden hand. Hand position was consistently misjudged as closer to the wrist (proximal bias) and, to a lesser extent, away from the thumb (ulnar bias). The magnitude of these biases depended on the localisation task (pointing vs. verbal), the orientation of the hand (straight vs. rotated), and the hand tested (left vs. right). Furthermore, the proximal location bias increased in size as the duration of the experiment increased, while the magnitude of ulnar bias remained stable through the experiment. Finally, the resultant maps of perceived hand location appear to replicate the previously reported overestimation of hand width and underestimation of finger length. Once again, the magnitude of these distortions is dependent on the task, orientation, and hand tested. These findings underscore the need to control and standardise each component of the hand localisation task in future studies.

<![CDATA[Potent Allosteric Dengue Virus NS5 Polymerase Inhibitors: Mechanism of Action and Resistance Profiling]]>

Flaviviruses comprise major emerging pathogens such as dengue virus (DENV) or Zika virus (ZIKV). The flavivirus RNA genome is replicated by the RNA-dependent-RNA polymerase (RdRp) domain of non-structural protein 5 (NS5). This essential enzymatic activity renders the RdRp attractive for antiviral therapy. NS5 synthesizes viral RNA via a “de novo” initiation mechanism. Crystal structures of the flavivirus RdRp revealed a “closed” conformation reminiscent of a pre-initiation state, with a well ordered priming loop that extrudes from the thumb subdomain into the dsRNA exit tunnel, close to the “GDD” active site. To-date, no allosteric pockets have been identified for the RdRp, and compound screening campaigns did not yield suitable drug candidates. Using fragment-based screening via X-ray crystallography, we found a fragment that bound to a pocket of the apo-DENV RdRp close to its active site (termed “N pocket”). Structure-guided improvements yielded DENV pan-serotype inhibitors of the RdRp de novo initiation activity with nano-molar potency that also impeded elongation activity at micro-molar concentrations. Inhibitors exhibited mixed inhibition kinetics with respect to competition with the RNA or GTP substrate. The best compounds have EC50 values of 1–2 μM against all four DENV serotypes in cell culture assays. Genome-sequencing of compound-resistant DENV replicons, identified amino acid changes that mapped to the N pocket. Since inhibitors bind at the thumb/palm interface of the RdRp, this class of compounds is proposed to hinder RdRp conformational changes during its transition from initiation to elongation. This is the first report of a class of pan-serotype and cell-active DENV RdRp inhibitors. Given the evolutionary conservation of residues lining the N pocket, these molecules offer insights to treat other serious conditions caused by flaviviruses.

<![CDATA[SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling]]>

Recessive mutations in the SDCCAG8 gene cause a nephronophthisis-related ciliopathy with Bardet-Biedl syndrome-like features in humans. Our previous characterization of the orthologous Sdccag8gt/gt mouse model recapitulated the retinal-renal disease phenotypes and identified impaired DNA damage response signaling as an underlying disease mechanism in the kidney. However, several other phenotypic and mechanistic features of Sdccag8gt/gt mice remained unexplored. Here we show that Sdccag8gt/gt mice exhibit developmental and structural abnormalities of the skeleton and limbs, suggesting impaired Hedgehog (Hh) signaling. Indeed, cell culture studies demonstrate the requirement of SDCCAG8 for ciliogenesis and Hh signaling. Using an affinity proteomics approach, we demonstrate that SDCCAG8 interacts with proteins of the centriolar satellites (OFD1, AZI1), of the endosomal sorting complex (RABEP2, ERC1), and with non-muscle myosin motor proteins (MYH9, MYH10, MYH14) at the centrosome. Furthermore, we show that RABEP2 localization at the centrosome is regulated by SDCCAG8. siRNA mediated RABEP2 knockdown in hTERT-RPE1 cells leads to defective ciliogenesis, indicating a critical role for RABEP2 in this process. Together, this study identifies several centrosome-associated proteins as novel SDCCAG8 interaction partners, and provides new insights into the function of SDCCAG8 at this structure.

<![CDATA[The Brain Effective Connectivity of Chinese during Rhyming Task]]>

With regard to brain language processing, the activation patterns have been well studied, and recently there are great interest in the connectivity models. The crucial brain areas for phonological processing involves left inferior frontal gyrus (LIFG), left inferior parietal lobule (LIPL) and left posterior middle temporal gyrus (LpMTG). Specially in Chinese processing, the left middle frontal gyrus (LMFG) is considered as an essential region. However, the connectivity pattern among these brain areas is not well understood. In this study, a rhyming experiment of Chinese was conducted, and the Dynamic causal modeling (DCM) and the Bayesian model selection (BMS) were used to examine the interaction between brain regions and choose the best model for rhyming task of Chinese. By examining the interactions, it was found that LMFG exerted inhibitory modulation on LIPL and LIFG; the phonological processing enhanced the connection from LIPL to LIFG and LMFG, which suggested the important roles of these connections for the increased phonological load; And LpMTG modulated LIFG and LMFG negatively, and LIPL positively under rhyming judgment task.

<![CDATA[Doing It Your Way: How Individual Movement Styles Affect Action Prediction]]>

Individuals show significant variations in performing a motor act. Previous studies in the action observation literature have largely ignored this ubiquitous, if often unwanted, characteristic of motor performance, assuming movement patterns to be highly similar across repetitions and individuals. In the present study, we examined the possibility that individual variations in motor style directly influence the ability to understand and predict others’ actions. To this end, we first recorded grasping movements performed with different intents and used a two-step cluster analysis to identify quantitatively ‘clusters’ of movements performed with similar movement styles (Experiment 1). Next, using videos of the same movements, we proceeded to examine the influence of these styles on the ability to judge intention from action observation (Experiments 2 and 3). We found that motor styles directly influenced observers’ ability to ‘read’ others’ intention, with some styles always being less ‘readable’ than others. These results provide experimental support for the significance of motor variability for action prediction, suggesting that the ability to predict what another person is likely to do next directly depends on her individual movement style.

<![CDATA[Kinematic Analyses of the Thumb during Simulated Posteroanterior Glide Mobilization]]>


Thumb problems are common in some health professionals such as physical therapists. The purpose of this case-control study is to investigate the influence of clinical experience and different mobilization techniques on the kinematics of the thumb.


Twenty-three participants without exposure to manual techniques (the Novice Group) and fifteen physical therapists with at least 3 years of orthopedic experience (the Experienced Group) participated. The kinematics of the thumb while performing 3 different simulated posteroanterior (PA) glide mobilization techniques on a load cell was monitored. These 3 techniques were: 1) unsupported, 2) with digital support and 3) with thumb interphalangeal joint supported by the index finger. The amount of forces exerted were 25% to 100% of maximum effort at 25% increments. The main effects of experience and technique on thumb kinematics were assessed.


Both experience and technique had main effects on the flexion/extension angles of the thumb joints. Experienced participants assumed a more flexed position at the carpometacarpal (CMC) joint, and the novice participants performed with angles closer to the neutral position (F = 7.593, p = 0.010). Participants’ metacarpophalangeal (MCP) joints were in a more flexed position while performing PA glide with thumb interphalangeal (IP) joint supported by the index as compared to the other two techniques (p < .001).


Negative correlations were generally obtained between the sagittal plane angles of adjacent thumb joints during mobilization/manipulation. Therapists are recommended to treat patient with more stable PA glide mobilization techniques, such as PA glide with thumb interphalangeal joint supported by the index finger, to prevent potential mobilization-related thumb disorders.

<![CDATA[Analysis of Hand and Wrist Postural Synergies in Tolerance Grasping of Various Objects]]>

Human can successfully grasp various objects in different acceptable relative positions between human hand and objects. This grasp functionality can be described as the grasp tolerance of human hand, which is a significant functionality of human grasp. To understand the motor control of human hand completely, an analysis of hand and wrist postural synergies in tolerance grasping of various objects is needed. Ten healthy right-handed subjects were asked to perform the tolerance grasping with right hand using 6 objects of different shapes, sizes and relative positions between human hand and objects. Subjects were wearing CyberGlove attaching motion tracker on right hand, allowing a measurement of the hand and wrist postures. Correlation analysis of joints and inter-joint/inter-finger modules were carried on to explore the coordination between joints or modules. As the correlation between hand and wrist module is not obvious in tolerance grasping, individual analysis of wrist synergies would be more practical. In this case, postural synergies of hand and wrist were then presented separately through principal component analysis (PCA), expressed through the principal component (PC) information transmitted ratio, PC elements distribution and reconstructed angle error of joints. Results on correlation comparison of different module movements can be well explained by the influence factors of the joint movement correlation. Moreover, correlation analysis of joints and modules showed the wrist module had the lowest correlation among all inter-finger and inter-joint modules. Hand and wrist postures were both sufficient to be described by a few principal components. In terms of the PC elements distribution of hand postures, compared with previous investigations, there was a greater proportion of movement in the thumb joints especially the interphalangeal (IP) and opposition rotation (ROT) joint. The research could serve to a complete understanding of hand grasp, and the design, control of the anthropomorphic hand and wrist.

<![CDATA[The LET Procedure for Prosthetic Myocontrol: Towards Multi-DOF Control Using Single-DOF Activations]]>

Simultaneous and proportional myocontrol of dexterous hand prostheses is to a large extent still an open problem. With the advent of commercially and clinically available multi-fingered hand prostheses there are now more independent degrees of freedom (DOFs) in prostheses than can be effectively controlled using surface electromyography (sEMG), the current standard human-machine interface for hand amputees. In particular, it is uncertain, whether several DOFs can be controlled simultaneously and proportionally by exclusively calibrating the intended activation of single DOFs. The problem is currently solved by training on all required combinations. However, as the number of available DOFs grows, this approach becomes overly long and poses a high cognitive burden on the subject. In this paper we present a novel approach to overcome this problem. Multi-DOF activations are artificially modelled from single-DOF ones using a simple linear combination of sEMG signals, which are then added to the training set. This procedure, which we named LET (Linearly Enhanced Training), provides an augmented data set to any machine-learning-based intent detection system. In two experiments involving intact subjects, one offline and one online, we trained a standard machine learning approach using the full data set containing single- and multi-DOF activations as well as using the LET-augmented data set in order to evaluate the performance of the LET procedure. The results indicate that the machine trained on the latter data set obtains worse results in the offline experiment compared to the full data set. However, the online implementation enables the user to perform multi-DOF tasks with almost the same precision as single-DOF tasks without the need of explicitly training multi-DOF activations. Moreover, the parameters involved in the system are statistically uniform across subjects.

<![CDATA[Expertise with unfamiliar objects is flexible to changes in task but not changes in class]]>

Perceptual expertise is notoriously specific and bound by familiarity; generalizing to novel or unfamiliar images, objects, identities, and categories often comes at some cost to performance. In forensic and security settings, however, examiners are faced with the task of discriminating unfamiliar images of unfamiliar objects within their general domain of expertise (e.g., fingerprints, faces, or firearms). The job of a fingerprint expert, for instance, is to decide whether two unfamiliar fingerprint images were left by the same unfamiliar finger (e.g., Smith’s left thumb), or two different unfamiliar fingers (e.g., Smith and Jones’s left thumb). Little is known about the limits of this kind of perceptual expertise. Here, we examine fingerprint experts’ and novices’ ability to distinguish fingerprints compared to inverted faces in two different tasks. Inverted face images serve as an ideal comparison because they vary naturally between and within identities, as do fingerprints, and people tend to be less accurate or more novice-like at distinguishing faces when they are presented in an inverted or unfamiliar orientation. In Experiment 1, fingerprint experts outperformed novices in locating categorical fingerprint outliers (i.e., a loop pattern in an array of whorls), but not inverted face outliers (i.e., an inverted male face in an array of inverted female faces). In Experiment 2, fingerprint experts were more accurate than novices at discriminating matching and mismatching fingerprints that were presented very briefly, but not so for inverted faces. Our data show that perceptual expertise with fingerprints can be flexible to changing task demands, but there can also be abrupt limits: fingerprint expertise did not generalize to an unfamiliar class of stimuli. We interpret these findings as evidence that perceptual expertise with unfamiliar objects is highly constrained by one’s experience.

<![CDATA[Manual Loading Distribution During Carrying Behaviors: Implications for the Evolution of the Hominin Hand]]>

The human hand is unparalleled amongst primates in its ability to manipulate objects forcefully and dexterously. Previous research has predominantly sought to explain the evolution of these capabilities through an adaptive relationship between more modern human-like anatomical features in the upper limb and increased stone tool production and use proficiency. To date, however, we know little about the influence that other manipulatively demanding behaviors may have had upon the evolution of the human hand. The present study addresses one aspect of this deficiency by examining the recruitment of the distal phalanges during a range of manual transportation (i.e., carrying) events related to hominin behavioral repertoires during the Plio-Pleistocene. Specifically, forces on the volar pad of each digit are recorded during the transportation of stones and wooden branches that vary in weight and size. Results indicate that in most instances, the index and middle fingers are recruited to a significantly greater extent than the other three digits during carrying events. Relative force differences between digits were, however, dependent upon the size and weight of the object transported. Carrying behaviors therefore appear unlikely to have contributed to the evolution of the robust thumb anatomy observed in the human hand. Rather, results suggest that the manual transportation of objects may plausibly have influenced the evolution of the human gripping capabilities and the 3rd metacarpal styloid process.

<![CDATA[Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation]]>

The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients. In Tbx hypomorphic mutants maintained on an INV mutant background, with situs inversus, the laterality of defects is reversed. Our data demonstrate an early, inherent asymmetry in the left and right limb-forming regions and that threshold levels of Tbx5 are required to overcome this asymmetry to ensure symmetric forelimb formation.

<![CDATA[Repayment policy for multiple loans]]>

The Repayment Policy for Multiple Loans is about a given set of loans and a monthly incoming cash flow: what is the best way to allocate the monthly income to repay such loans? In this article, we close the almost 20-year-old open question about how to model the repayment policy for multiple loans problem together with its computational complexity. Thus, we propose a mixed integer linear programming model that establishes an optimal repayment schedule by minimizing the total amount of cash required to repay the loans. We prove that the most employed repayment strategies, such as the highest interest debt and the debt snowball methods, are not optimal. Experimental results on simulated cases based on real data show that our methodology obtains on average more than 4% of savings, that is, the debtor pays approximately 4% less to the bank or loaner, which is a considerable amount in finances. In certain cases, the debtor can save up to 40%.

<![CDATA[Visual Cues of Object Properties Differentially Affect Anticipatory Planning of Digit Forces and Placement]]>

Studies on anticipatory planning of object manipulation showed initial task failure (i.e., object roll) when visual object shape cues are incongruent with other visual cues, such as weight distribution/density (e.g., symmetrically shaped object with an asymmetrical density). This suggests that shape cues override density cues. However, these studies typically only measured forces, with digit placement constrained. Recent evidence suggests that when digit placement is unconstrained, subjects modulate digit forces and placement. Thus, unconstrained digit placement might be modulated on initial trials (since it is an explicit process), but not forces (since it is an implicit process). We tested whether shape and density cues would differentially influence anticipatory planning of digit placement and forces during initial trials of a two-digit object manipulation task. Furthermore, we tested whether shape cues would override density cues when cues are incongruent. Subjects grasped and lifted an object with the aim of preventing roll. In Experiment 1, the object was symmetrically shaped, but with asymmetrical density (incongruent cues). In Experiment 2, the object was asymmetrical in shape and density (congruent cues). In Experiment 3, the object was asymmetrically shaped, but with symmetrical density (incongruent cues). Results showed differential modulation of digit placement and forces (modulation of load force but not placement), but only when shape and density cues were congruent. When shape and density cues were incongruent, we found collinear digit placement and symmetrical force sharing. This suggests that congruent and incongruent shape and density cues differentially influence anticipatory planning of digit forces and placement. Furthermore, shape cues do not always override density cues. A continuum of visual cues, such as those alluding to shape and density, need to be integrated.

<![CDATA[Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking]]>

The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01–23.84 μM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development.

<![CDATA[Degenerative Changes in the Cervical Spine Are More Common in Middle-Aged Individuals with Thalidomide Embryopathy than in Healthy Controls]]>


Thalidomide was used as a sedative drug for pregnant women in the 1950–60:s and resulted in children born with thalidomide embryopathy (TE), including upper limb malformations. These may alter the motion pattern of the cervical spine by the use of head/shoulder and mouth grip.


To compare degenerative changes in the cervical spine in TE individuals with healthy controls (CTR).

Methods and Procedures

Twenty-seven middle-aged TE individuals and 27 age- and gender-matched CTR were examined by cervical spine MRI. The presence of malformations, disc herniation(s), osteophytes, nerve and medullary compression and the degree of disc degeneration (DD) were evaluated.

Outcomes and Results

Significantly higher degree of DD was seen in the TE group compared with the controls (p<0.001). Similar frequencies of disc herniation and disc space narrowing were observed in the two groups, but more foraminal narrowing was seen in the TE group (p = 0.002). DD was observed relatively frequently at all cervical levels in the TE group, however, mainly at the two lower levels in the CTR.

Conclusions and Implications

Middle-aged individuals with TE have a higher frequency of degenerative changes in the cervical spine than controls, possibly caused by an altered load on the cervical spine.

<![CDATA[Adaptation of the Transverse Carpal Ligament Associated with Repetitive Hand Use in Pianists]]>

The transverse carpal ligament (TCL) plays a critical role in carpal tunnel biomechanics through interactions with its surrounding tissues. The purpose of this study was to investigate the in vivo adaptations of the TCL’s mechanical properties in response to repetitive hand use in pianists using acoustic radiation force impulse (ARFI) imaging. It was hypothesized that pianists, in comparison to non-pianists, would have a stiffer TCL as indicated by an increased acoustic shear wave velocity (SWV). ARFI imagining was performed for 10 female pianists and 10 female non-pianists. The median SWV values of the TCL were determined for the entire TCL, as well as for its radial and ulnar portions, rTCL and uTCL, respectively. The TCL SWV was significantly increased in pianists relative to non-pianists (p < 0.05). Additionally, the increased SWV was location dependent for both pianist and non-pianist groups (p < 0.05), with the rTCL having a significantly greater SWV than the uTCL. Between groups, the rTCL SWV of pianists was 22.2% greater than that of the non-pianists (p < 0.001). This localized increase of TCL SWV, i.e. stiffening, may be primarily attributable to focal biomechanical interactions that occur at the radial TCL aspect where the thenar muscles are anchored. Progressive stiffening of the TCL may become constraining to the carpal tunnel, leading to median nerve compression in the tunnel. TCL maladaptation helps explain why populations who repeatedly use their hands are at an increased risk of developing musculoskeletal pathologies, e.g. carpal tunnel syndrome.

<![CDATA[Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface]]>

Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5’-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quaternary organization of the functional enzyme are available. We report the crystal structure of dengue virus full-length NS5, where eight molecules of NS5 are arranged as four independent dimers in the crystallographic asymmetric unit. The relative orientation of each monomer within the dimer, as well as the orientations of the MTase and RdRp domains within each monomer, is conserved, suggesting that these structural arrangements represent the biologically relevant conformation and assembly of this multi-functional enzyme. Essential interactions between MTase and RdRp domains are maintained in the NS5 dimer via inter-molecular interactions, providing evidence that flavivirus NS5 can adopt multiple conformations while preserving necessary interactions between the MTase and RdRp domains. Furthermore, many NS5 residues that reduce viral replication are located at either the inter-domain interface within a monomer or at the inter-molecular interface within the dimer. Hence the X-ray structure of NS5 presented here suggests that MTase and RdRp activities could be coordinated as a dimer during viral genome replication.

<![CDATA[Measuring 3D Hand and Finger Kinematics—A Comparison between Inertial Sensing and an Opto-Electronic Marker System]]>

Objective analysis of hand and finger kinematics is important to increase understanding of hand function and to quantify motor symptoms for clinical diagnosis. The aim of this paper is to compare a new 3D measurement system containing multiple miniature inertial sensors (PowerGlove) with an opto-electronic marker system during specific finger tasks in three healthy subjects. Various finger movements tasks were performed: flexion, fast flexion, tapping, hand open/closing, ab/adduction and circular pointing. 3D joint angles of the index finger joints and position of the thumb and index were compared between systems. Median root mean square differences of the main joint angles of interest ranged between 3.3 and 8.4deg. Largest differences were found in fast and circular pointing tasks, mainly in range of motion. Smallest differences for all 3D joint angles were observed in the flexion tasks. For fast finger tapping, the thumb/index amplitude showed a median difference of 15.8mm. Differences could be explained by skin movement artifacts caused by relative marker movements of the marker system, particularly during fast tasks; large movement accelerations and angular velocities which exceeded the range of the inertial sensors; and by differences in segment calibrations between systems. The PowerGlove is a system that can be of value to measure 3D hand and finger kinematics and positions in an ambulatory setting. The reported differences need to be taken into account when applying the system in studies understanding the hand function and quantifying hand motor symptoms in clinical practice.