Biomedical subjects

J R Flanagan

Publications and source records attributed to J R Flanagan.

At least 19 recordsLinked to original sources

PubMed1997

The role of internal models in motion planning and control: evidence from grip force adjustments during movements of hand-held loads.

We investigated the issue of whether or not the CNS makes use of an internal model of the motor apparatus in planning and controlling arm movements. In particular, we tested the ability of subjects to predict different hand-held loads by examining grip force adjustments used to stabilize the load in the hand during arm movements. Subjects grasped a manipulandum using a precision grip with the tips of the thumb and index finger on either side. The grip force (normal to the contact surfaces) and the load force (tangential to the surfaces) were measured, along with the trajectory of the hand. The manipulandum was attached to two servo-controlled linear motors used to create inertial and viscous loads as well as a composite load, including inertial, viscous, and elastic components. The form of the hand trajectory was independent of load for some subjects but varied systematically across load conditions in others. Nevertheless, under all load conditions and in all subjects, grip force was modulated in parallel with, and thus anticipated, fluctuations in load force despite the marked variation in the form of the load function. This indicates that the CNS is able to predict the load force and the kinematics of hand movement on which the load depends. We suggest this prediction is based on an internal model of the motor apparatus and external load and is used to determine the grip forces required to stabilize the load.

Adaptation, Physiological↗

PubMed1997

Anticipatory postural adjustments in stance and grip.

The reactive forces and torques associated with moving a hand-held object between two points are potentially destabilising, both for the object's position in the hand and for body posture. Previous work has demonstrated that there are increases in grip force ahead of arm motion that contribute to object stability in the hand. Other studies have shown that early postural adjustments in the legs and trunk minimise the potential perturbing effects on body posture of rapid voluntary arm movement. This paper documents the concurrent evolution of grip force and postural adjustments in anticipation of dynamic and static loads. Subjects held a manipulandum in precision grasp between thumb and index finger and pulled or pushed either a dynamic or a fixed load horizontally towards or away from the body (the grasp axis was orthogonal to the line of the load force). A force plate measured ground reaction torques, and force transducers in the manipulandum measured the load (tangential) and grip (normal) forces acting on the thumb and finger. In all conditions, increases in grip force and ground reaction torque preceded any detectable rise in load force. Rates of change of grip force and ground reaction torque were correlated, even after partialling out a common dependence on load force rate. Moreover, grip force and ground reaction torque rates at the onset of load force were correlated. These results imply the operation of motor planning processes that include anticipation of the dynamic consequences of voluntary action.

Adult↗

PubMed1997

Tangential torque effects on the control of grip forces when holding objects with a precision grip.

When we manipulate small objects, our fingertips are generally subjected to tangential torques about the axis normal to the grasp surface in addition to linear forces tangential to the grasp surface. Tangential torques can arise because the normal force is distributed across the contact area rather than focused at a point. We investigated the effects of tangential torques and tangential forces on the minimum normal forces required to prevent slips (slip force) and on the normal forces actually employed by subjects to hold an object in a stationary position with the use of the tips of the index finger and thumb. By changing the location of the object's center of gravity in relation to the grasp surface, various levels of tangential torque (0-50 N x mm) were created while the subject counteracted object rotation. Tangential force (0-3.4 N) was varied by changing the weight of the object. The flat grasp surfaces were covered with rayon, suede, or sandpaper, providing differences in friction in relation to the skin. Under zero tangential force, both the employed normal force and the slip force increased in proportion to tangential torque with a slope that reflected the current frictional condition. Likewise, with pure tangential force, these forces increased in proportion to tangential force. The effects of combined tangential torques and tangential forces on the slip force were primarily additive, but there was a significant interaction of these variables. Specifically, the increase in slip force for a given increment in torque decreases as a function of tangential force. A mathematical model was developed that successfully predicted slip force from tangential torque, tangential force, and an estimate of coefficient of static friction in the digit-surface interface. The effects of combined tangential torques and forces on the employed normal force showed the same pattern as the effects on the slip force. The safety margin against frictional slips, measured as the difference between the employed normal force and the slip force, was relatively small and constant across all tangential force and torque levels except at small torques (< 10 N x mm). There was no difference in safety margin between the digits. In conclusion, tangential torque strongly influences the normal force required for grasp stability. When controlling normal force, people take into account, in a precise fashion, the slip force reflecting both tangential force and tangential torque and their interaction as well as the current frictional condition in the object-digit interface.

Adult↗

PubMed1997

Effects of surface texture and grip force on the discrimination of hand-held loads.

In this paper, we report the results from two experiments in which subjects were required to discriminate horizontal load forces applied to a manipulandum held with a precision grip. The roughness (and hence friction) of the grip surfaces and required grip force were manipulated. In the first experiment, subjects were instructed to judge the load while maintaining hand position and not letting the manipulandum slip. It was found that performance was influenced by surface texture; a given load was judged to be greater when the surface texture was smooth than when it was rough. This result is consistent with a previous study based on lifting objects and indicates that the effect of surface texture applies to loads in general and not just to gravitational loads (i.e., weight). To test whether the load acting on a smooth object is judged to be greater because the grip force required to prevent it from slipping is larger, a second experiment was carried out. Subjects used a visual feedback display to maintain the same grip force for smooth and rough manipulandum surfaces. In this case, there was no effect of surface texture on load perception. These results provide evidence that perceived load depends on the grip force used to resist the load. The implications of these results in terms of central and peripheral factors underlying load discrimination are considered.

Adolescent↗

PubMed1996

Evolution of a legacy system to a Web patient record server: leveraging investment while opening the system.

A layered system is under development to enhance our legacy system as a backend in a WEB-enabled system. Each layer of the system has defined functionality, leverages the investment in the layer below, and follows the strategy of reducing support requirements for workstations. The mainframe system provides administrative integration of sub-systems, security, and the central data repository for most information. The second layer is a graphical user interface (GUI) to the system for Windows platforms. Support needs are limited by relying chiefly on X-terminals and application servers. The "Intranet" layer is a WEB Server building upon the second layer gateways to provide platform-independent access to selected information and images. The fourth layer, under evaluation, will extend access to the central data repository for Internet users of web browsers that support private-key/public-key encryption.

Computer Communication Networks↗

PubMed1995

The stability of precision grip forces during cyclic arm movements with a hand-held load.

In this paper we examine the coordination of grip force and load during brisk cyclic arm movements with a hand-held object under a range of conditions. We show that, regardless of the surface texture of the object or movement frequency, grip force is modulated in parallel with load. Thus, the tight coupling between grip force and load observed in short-duration tasks such as lifting or point-to-point movements is also seen in longer-duration cyclic movements. Moreover, the gain of the relation between grip force and load remains essentially constant over time. Across conditions, we find a dissociation between the gain of the relation between grip force and load and the grip force offset. With a more slippery surface texture both the gain and offset increase, whereas increases in frequency lead to an increase in the offset but a decrease in gain. This suggests that these two parameters are under independent high-level control. We also observe that when subjects were instructed to maintain a high-baseline grip force during the movement, grip force was still modulated with load even though an increase in grip was not necessary to prevent slip. This suggests that there is an obligatory coupling between grip force and load. This coupling might be subserved by low-level mechanisms not under high-level control.

Adult↗

PubMed1995

Trajectory adaptation to a nonlinear visuomotor transformation: evidence of motion planning in visually perceived space.

1. Although reaching movements are characterized by hand paths that tend to follow roughly straight lines in Cartesian space, a fundamental issue is whether this reflects constraints associated with perception or movement production. 2. To address this issue, we examined two-joint planar reaching movements in which we manipulated the mapping between actual and visually perceived motion. In particular, we used a nonlinear transformation such that straight line hand paths in Cartesian space would result in curved paths in perceived space and vice versa. 3. Under these conditions, subjects learned to make straight line paths in perceived space even though the paths of the hand in Cartesian space were markedly curved. In contrast, when the motion was perceived in Cartesian space (i.e., in the absence of a nonlinear distortion), straight line hand paths were observed. 4. These findings suggest that visually guided reaching movements are planned in a perceptual frame of reference. Reaching movements in the horizontal plane are adapted so as to produce straight lines in visually perceived space.

Adaptation, Physiological↗

PubMed1995

Effects of surface texture on weight perception when lifting objects with a precision grip.

In this paper, we show that, when lifting an object using a precision grip with the distal pads of the thumb and index finger at its sides, the perceived weight depends on the object's surface texture. The smoother the surface texture, the greater the perceived weight. We suggest that a smoother object is judged to be heavier because the grip force, normal to the surface, required to prevent it from slipping is greater. The possibility of there being an influence of surface texture per se is excluded by a second experiment that employed a variant of the precision grip in which the thumb supports the weight of the object from underneath. With the grip oriented in this way, there is no need to match grip force to surface texture and, under these conditions, there is no effect of surface texture on weight perception. In the first two experiments, the test and comparison weights were lifted successively by the same hand. In a third experiment, the effect of surface texture was replicated for sequential lifts made with separate hands. Thus, the effect is not restricted to comparisons made with the same hand.

Adolescent↗

PubMed1995

Autologous stimulation of YY1 transcription factor expression: role of an insulin-like growth factor.

YY1 is believed to be a constitutive factor, present in all cell types, affecting the transcription of a large number of genes. Experiments in this report demonstrated that YY1 RNA expression in NIH3T3 cells was modulated by media factors, either exogenously added to the media or elaborated by the NIH3T3 cells themselves. This autologous stimulation of YY1 expression was in proportion to the density of cells and was time dependent. Sparsely plated cells lost YY1 RNA expression within hours after being placed under fresh, serum-free media and lost YY1 protein expression by 24 h. Subsequent recurrence of YY1 expression in serum-deprived NIH3T3 cells was significantly decreased by adding monoclonal anti-insulin-like growth factor (IGF)-1 to the media. Radioimmunoassay showed that NIH3T3 cells secreted IGF-1 into the media for up to 72 h after being deprived of serum in the media but did not do so after they became quiescent. In quiescent NIH3T3 cells, YY1 expression was low or absent but was rapidly stimulated by exposure of the quiescent cells to media-containing serum. Exogenous growth factors, either whole serum or purified IGF-1, stimulated YY1 expression equally well. The rapid responses of YY1 expression to growth factor deprivation and replacement suggested the possibility that YY1 may mediate some of the intranuclear responses to autologous stimulation by IGF-1.

3T3 Cells↗

PubMed1995

Cost-effective health information systems: user-driven internal development at the University of Iowa.

GOALS: The Information Network For Online Retrieval & Medical Management (INFORMM), health information system (HIS) for the University of Iowa Hospitals and Clinics (UIHC), was analyzed with regard to development of a Computer-Based Patient Record (CBPR) in a cost-effective manner. The analysis: i) profiles INFORMM system functionality; ii) displays INFORMM use and satisfaction among physicians, nurses, and other hospital employees; iii) characterizes dynamics affecting INFORMM growth; and iv) evaluates the cost of a system of internal-development of software. DATA SOURCES: INFORMM utilization for 1989, 1994, and 1995; service requests from users for the years 1985, 1990, and 1994; 1994 MECON-PEERx data; gap analysis user survey conducted by an independent consulting firm. MAIN RESULTS: 1) Physician use has been dominated by a single function: retrieval of laboratory results. 2) Nurse use of the system was more diverse. A recent surge of nurse and physician use resulted from the introduction of online documentation of nursing care. 3) Overall use has been predominantly by non-clinician users, no one function dominating their pattern of use. 4) User service requests were predominantly from the non-clinician group of users. Requests from non-physician groups have been coordinated by a limited number of representatives of those groups, unlike requests from physicians. 5) The UIHC HIS ranked high in user satisfaction. 6) The overall cost of the UIHC HIS system is relatively low as a percentage of the gross operating budget or as a ratio to the volume of patient activities in this medical center. CONCLUSIONS: Internal development of INFORMM has been a cost-effective solution to the information demands of nursing staff and other users. INFORMM system composition reflects the quantity and organization of user requests. Satisfying the needs of physicians requires a change in the manner in which physician needs are assessed.

Attitude to Computers↗

PubMed1994

Grip-load force coupling: a general control strategy for transporting objects.

The authors examined the coupling of grip force and load force during point-to-point and cyclic arm movements while holding an object in a variety of grips, including 1- and 2-handed grips and "inverted" grips. In all grips, grip force is modulated in phase with fluctuations in load force that are induced by the arm movement. The tight temporal coupling between grip force and load force seen when moving an object held in a precision grip (J. R. Flanagan, J. Tresilian, & A. M. Wing, 1993) is observed in other grips. The control of precision grip force during whole-body jumping movements was also investigated. Grip force was modulated in phase with changes in load force induced by jumping even though the arm's joint angles were fixed. The tight temporal coupling between grip force and load force during object transport reflects a general control strategy that is not specific to any particular grip or mode of transport. Models of the coordination of grasp and transport in prehensile behaviors are discussed.

Acceleration↗

PubMed1993

Coupling of grip force and load force during arm movements with grasped objects.

Numerous studies have investigated the kinematics of arm movements; others have examined grip forces during static holding of objects. However, the coordination of grip force and arm movement when moving grasped objects has not been documented. We show that grip force is finely modulated in phase with load force during movements with grasped objects in which load force varies with acceleration. A tight coupling between grip and load force is seen in point-to-point and cyclic movements of varying rate and direction. We conclude that in transporting an object, the programming of grip force is part and parcel of the process of planning the arm movement.

Arm↗

PubMed1993

Modulation of grip force with load force during point-to-point arm movements.

In this paper, we examine grip forces and load forces during point-to-point arm movements with objects grasped with a precision grip. We demonstrate that grip force is finely modulated with load force. Variations in load force arise from inertial forces related to movement; grip force rises as the load force increases and falls as load force decreases. The same finding is observed in vertical and horizontal movements performed at various rates. In vertical movements, maximum grip force coincides in time with maximum load force. The maxima occur early in upward and later in downward movements. In horizontal movements, where peaks in load force are observed during both the acceleratory and deceleratory phases, grip force rises at the beginning of the movement and remains high until the end. The results suggest that when moving an object with the hand the programming of grip force is an integral part of the planning process.

Adolescent↗

PubMed1992

Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus.

The long terminal repeat of Moloney murine leukemia virus (MuLV) contains the upstream conserved region (UCR). The UCR core sequence, CGCCATTTT, binds a ubiquitous nuclear factor and mediates negative regulation of MuLV promoter activity. We have isolated murine cDNA clones encoding a protein, referred to as UCRBP, that binds specifically to the UCR core sequence. Gel mobility shift assays demonstrate that the UCRBP fusion protein expressed in bacteria binds the UCR core with specificity identical to that of the UCR-binding factor in the nucleus of murine and human cells. Analysis of full-length UCRBP cDNA reveals that it has a putative zinc finger domain composed of four C2H2 zinc fingers of the GLI subgroup and an N-terminal region containing alternating charges, including a stretch of 12 histidine residues. The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR-binding factor. Transient transfection of an expressible UCRBP cDNA into fibroblasts results in down-regulation of MuLV promoter activity, in agreement with previous functional analysis of the UCR. Recently three groups have independently isolated human and mouse UCRBP. These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno-associated virus P5 promoter and elements in the immunoglobulin light- and heavy-chain genes, as well as elements in ribosomal protein genes. These results indicate that UCRBP has unusually diverse DNA-binding specificity and as such is likely to regulate expression of many different genes.

Amino Acid Sequence↗

PubMed1991

Negative regulation of the major histocompatibility complex class I promoter in embryonal carcinoma cells.

Transcription of major histocompatibility complex (MHC) class I genes is negatively regulated in undifferentiated F9 mouse embryonal carcinoma cells via the conserved upstream regulatory region. This region contains constitutive enhancers and an inducible enhancer, the interferon consensus sequence (ICS), that is responsible for interferon-induced transcription. A series of mutations in the ICS, but not in the enhancer elements, resulted in an increase in expression of the MHC class I promoter in F9 cells. However, these ICS mutants did not increase promoter activity in F9 cells differentiated after retinoic acid treatment. Results of mobility-shift DNA-binding assays and methylation interference experiments showed that undifferentiated F9 cells contained a factor(s) that bound to a sequence within the 5' and central part of the ICS. This binding site, termed the MHC negative regulatory element (NRE), coincided with the site of mutations that increased promoter activity in F9 cells and was distinct from the element to which interferon-response factors bind. The factor(s) that binds to the MHC NRE was not detected in differentiated F9 cells treated with retinoic acid or in other cells expressing MHC class I genes. Finally, introduction of concatenated, double-stranded NRE oligomers, but not oligomers of unrelated sequences, into F9 cells abolished negative regulation of the MHC class I promoter activity, providing evidence that the NRE binding factor is responsible for repression of the MHC class I genes in F9 cells.

Animals↗

PubMed1991

Kinematics and control of frog hindlimb movements.

1. The determinants of the motion path of the hindlimb were explored in both intact and spinal frogs. In the spinal preparations the kinematic properties of withdrawal and crossed-extension reflexes were studied. In the intact frog the kinematics of withdrawal and swimming movements were examined. Frog hindlimb paths were described in joint angle (intrinsic) coordinates rather than limb endpoint (extrinsic) coordinates. 2. To study withdrawal and crossed-extension reflexes, the initial angles at the hip, knee, and ankle were varied. Withdrawal and crossed extension were recorded in three dimension (3-D) with the use of an infra-red spatial imaging system. Swimming movements against currents of different speeds were obtained with high-speed film. 3. Three strategies were considered related to the form of the hypothesized equilibrium paths specified by the nervous system: all trajectories lie on a single line in angular coordinates; all trajectories are directed toward a common final position; and all trajectories have the same direction independent of initial joint configuration. 4. Joint space paths in withdrawal were found to be straight and parallel independent of the initial joint configuration. The hip and knee were found to start simultaneously and in 75% of the conditions tested to reach maximum velocity simultaneously. Hip-knee maximum velocity ratios were similar in magnitude over differences in initial joint angles. This is consistent with the observation of parallel paths and supports the view that the nervous system specifies a single direction for equilibrium trajectories. 5. Straight line paths with slopes similar to those observed in withdrawal in the spinal preparation were found in swimming movements in the intact frog. Straight line paths in joint space are consistent with the idea that swimming and withdrawal are organized and controlled in a joint-level coordinate system. The similarities observed between spinal and intact preparations suggest that a common set of constructive elements underlies these behaviors. 6. Path curvature was introduced when joint limits were approached toward the end of the movement. Depending on the initial joint angles, the joint movements ended at different times. When initial joint angles were unequal, joints moving from smaller initial angles reached their functional limits earlier and stopped first. 7. In withdrawal and crossed extension in the spinal frog, velocity profiles at a given joint were similar over the initial portion of the curve for movements of different amplitude. This is consistent with the idea that withdrawal and crossed-extension movements of different amplitude are produced by a constant rate of shift of the equilibrium position.

Animals↗

PubMed1990

An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.

Interferons (IFNs) induce transcription of major histocompatibility complex (MHC) class I genes through the conserved IFN consensus sequence (ICS) that contains an IFN response motif shared by many IFN-regulated genes. By screening mouse lambda ZAP expression libraries with the ICS as a probe, we isolated a cDNA clone encoding a protein that binds the ICS, designated ICSBP. Protein blot analysis with labeled oligonucleotide probes showed that ICSBP binds not only the MHC class I ICS but also IFN response motifs of many IFN-regulated genes, as well as a virus-inducible element of the IFN-beta gene. The ICSBP cDNA encodes 424 amino acids and a long 3' untranslated sequence. The N-terminal 115 amino acids correspond to a putative DNA-binding domain and show significant sequence similarity with other cloned IFN response factors (IRF-1 and IRF-2). Because of the structural similarity and shared binding specificity, we conclude that ICSBP is a third member of the IRF gene family, presumably playing a role in IFN- and virus-mediated regulation of many genes. Although IRF-1 and IRF-2 share some similarity in their C-terminal regions, ICSBP shows no similarity to IRF-1 or IRF-2 in this region, suggesting that it is more distantly related. We show that ICSBP mRNA is expressed predominantly in lymphoid tissues and is inducible preferentially by IFN-gamma. The induction by IFN-gamma appears to be predominant in lymphocytes and macrophages, implying that ICSBP plays a regulatory role in cells of the immune system. The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression.

Amino Acid Sequence↗

PubMed1990

Regulation of the mouse alpha A-crystallin gene: isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes.

We have shown by site-directed mutagenesis that the sequence between positions -69 and -40 of the mouse alpha A-crystallin gene is crucial for tissue-specific gene expression in a transfected mouse lens epithelial cell line transformed with the early region of simian virus 40. Gel retardation experiments with synthetic oligodeoxynucleotides revealed a mouse lens nuclear protein which bound specifically to the palindromic sequence 5'-GGGAAATCCC-3' at positions -66 to -57 in the alpha A-crystallin promoter. By screening a bacteriophage lambda gt11 expression library of the transformed lens cells, we isolated a 2.5-kilobase-pair cDNA encoding a fusion protein which bound to this sequence and to the regulatory element of the major histocompatibility complex (MHC) class I gene. This cDNA hybridized to a 10-kilobase-pair polyadenylated RNA present in many different tissues, including lens. It encoded a protein, tentatively called alpha A-CRYBP1, containing at least two zinc fingers. alpha A-CRYBP1 is either homologous or very similar to the human nuclear proteins MBP-1 (Baldwin et al., Mol. Cell. Biol. 10:1406-1414, 1990), PRDII-BFI (Fan and Maniatis, Genes Dev. 4:29-42, 1990), and HIV-EP1 (Maekawa et al., J. Biol. Chem. 264:14591-14593, 1989), which bind to regulatory elements of the MHC class I, beta interferon, and human immunodeficiency virus genes, respectively. Our results suggest that the lens-specific alpha A-crystallin, MHC class I, beta interferon and other genes have a similar cis-acting DNA regulatory motif that shares alpha A-CRYBPI, MBP-1, PRDII-BF1, HIV-EP1, or other closely related proteins as trans-acting factors.

Amino Acid Sequence↗