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PubMed2006

Matrix factorization algorithms for the identification of muscle synergies: evaluation on simulated and experimental data sets.

Several recent studies have used matrix factorization algorithms to assess the hypothesis that behaviors might be produced through the combination of a small number of muscle synergies. Although generally agreeing in their basic conclusions, these studies have used a range of different algorithms, making their interpretation and integration difficult. We therefore compared the performance of these different algorithms on both simulated and experimental data sets. We focused on the ability of these algorithms to identify the set of synergies underlying a data set. All data sets consisted of nonnegative values, reflecting the nonnegative data of muscle activation patterns. We found that the performance of principal component analysis (PCA) was generally lower than that of the other algorithms in identifying muscle synergies. Factor analysis (FA) with varimax rotation was better than PCA, and was generally at the same levels as independent component analysis (ICA) and nonnegative matrix factorization (NMF). ICA performed very well on data sets corrupted by constant variance Gaussian noise, but was impaired on data sets with signal-dependent noise and when synergy activation coefficients were correlated. Nonnegative matrix factorization (NMF) performed similarly to ICA and FA on data sets with signal-dependent noise and was generally robust across data sets. The best algorithms were ICA applied to the subspace defined by PCA (ICAPCA) and a version of probabilistic ICA with nonnegativity constraints (pICA). We also evaluated some commonly used criteria to identify the number of synergies underlying a data set, finding that only likelihood ratios based on factor analysis identified the correct number of synergies for data sets with signal-dependent noise in some cases. We then proposed an ad hoc procedure, finding that it was able to identify the correct number in a larger number of cases. Finally, we applied these methods to an experimentally obtained data set. The best performing algorithms (FA, ICA, NMF, ICAPCA, pICA) identified synergies very similar to one another. Based on these results, we discuss guidelines for using factorization algorithms to analyze muscle activation patterns. More generally, the ability of several algorithms to identify the correct muscle synergies and activation coefficients in simulated data, combined with their consistency when applied to physiological data sets, suggests that the muscle synergies found by a particular algorithm are not an artifact of that algorithm, but reflect basic aspects of the organization of muscle activation patterns underlying behaviors.

Algorithms↗

PubMedDate not supplied

Desperately seeking synergy.

Corporate executives have strong biases in favor of synergy, and those biases can lead them into ill-advised attempts to force business units to cooperate--even when the ultimate benefits are unclear. But executives can separate the real opportunities from the mirages, say Michael Goold and Andrew Campbell. They simply need to take a more disciplined approach to synergy. These biases take four forms. First comes the synergy bias, which leads executives to overestimate the benefits and underestimate the costs of synergy. Then comes the parenting bias, a belief that synergy will be captured only by cajoling or compelling business units to cooperate. The parenting bias is usually accompanied by the skills bias--the assumption that whatever know-how is required to achieve synergy will be available within the organization. Finally, executives fall victim to the upside bias, which causes them to concentrate so hard on the potential benefits of synergy that they overlook the possible downside risks. In combination, these four biases make synergy seem more attractive and more easily achievable than it truly is. As a result, corporate executives often launch initiatives that ultimately waste time and money and sometimes even severely damage their businesses. To avoid such failures, executives need to subject all synergy opportunities to a clear-eyed analysis that clarifies the benefits to be gained, examines the potential for corporate involvement, and takes into account the possible downsides. Such a disciplined approach will inevitably mean that fewer initiatives will be launched. But those that are pursued will be far more likely to deliver substantial gains.

Cooperative Behavior↗

PubMed2006

Elderly show decreased adjustments of motor synergies in preparation to action.

BACKGROUND: Aging is associated with decreased manual dexterity. Recent findings have identified changes in multi-finger synergies in elderly individuals. The purpose of current work was to study age-related changes in adjustments of multi-finger synergies in preparation to a quick targeted force pulse production task. METHODS: Right-handed elderly and young subjects produced quick force pulses by pressing on individual force sensors with the four fingers of the right hand. Prior to the force pulse, the subjects produced a constant low level of the total force. An index of multi-finger synergies was computed across trials for each time sample for each subject and each condition. FINDINGS: During steady-state force production, subjects showed co-variation of commands to fingers that stabilized the total force. An index of this co-variation started to decrease prior to the initiation of the force pulse (anticipatory synergy adjustment). Anticipatory synergy adjustments in young subjects started earlier and were larger than in elderly subjects. In particular, young and elderly subjects showed significant anticipatory synergy adjustments starting about 150ms and about 50ms prior to the force pulse initiation, respectively. There were no significant differences between the two groups in other indices of performance such as reaction time, time to peak force, and magnitude of the peak force. INTERPRETATION: We conclude that healthy aging is associated with decreased feed-forward adjustments of multi-finger synergies in preparation to action. This may contribute to the age-related decline in the hand function. Based on similarities in age-related changes in anticipatory postural adjustments and anticipatory synergy adjustments we suggest a hypothesis that the two phenomena may share common mechanisms.

Adult↗

PubMed1993

Synergies and strategies underlying normal and vestibulary deficient control of balance: implication for neuroprosthetic control.

Future developments of neuroprosthetic control will probably permit locomotion and posture to be maintained without the aid of crutches and will therefore require some form of balance control. Three fundamental questions will arise. First, the question of the location of imbalance-sensing transducers must be assessed. Secondly, the synergy, which is the relative amplitude and timing of muscle activity, and/or the strategy of joint torques required to re-establish a stable posture for different types of balance disturbances must be addressed. Thirdly, the control laws that map either trunk muscle activity or imbalance-sensing transducer outputs into multi-joint postural control of standing by paraplegic individuals must be generated. The most appropriate means of gathering the relevant information applicable to neuroprosthetic control systems is through the detailed analysis of normal and non-normal human models. In order to gain such detailed insights into normal balance control and its dependence on head angular and linear accelerations, the synergy and strategy of balance corrections in normal subjects or patients with vestibular deficits were investigated for two types of support surface perturbation, a dorsiflexion rotation (ROT) and a rearward translation (TRANS). These experimentally induced perturbations to upright stance were adjusted to cause equal amplitudes of ankle dorsiflexion, thus providing additional information about the role of lower leg proprioception on balance control. Synergies defined on the basis of peak cross-correlations of each recorded muscle's EMG to that of the largest muscle response were significantly different for TRANS and ROT. Translation synergies consisted of a sequential coactivation at several levels (soleus and abdominals some 30 msec before hamstrings, and trapezius some 15 msec before paraspinals), whereas the sequential activation of paraspinals and tibialis anterior dominated the balance synergy to ROT. Likewise, response strategies, defined using cross-correlations of joint torques, differed. That for TRANS was organised as a multi-link strategy with neck torques leading those of all other joints by 40 msec or more; hip joint lead ankle torques by 30 msec. That for ROT was organised around hip and ankle torques without a major correlation to neck torques. Vestibulary deficient subjects developed weaker synergies with respect to subjects with normal balance systems under eyes-open conditions and there was no clear synergy with eyes closed. Consequently, hip torques were delayed some 180 msec with respect to ankle torques, and correlations to neck torques were completely out of phase under eyes-closed conditions. Fundamental changes in TRANS synergies and strategies also occurred in vestibulary deficient subjects for eyes-open and eyes-closed conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Ankle↗

PubMed1984

Neuromotor synergies as a basis for coordinated intentional action.

Although neurally based units of action (neuromotor synergies) have often been proposed as a possible basis for coordinated intentional as well as automatic actions, the idea has rarely been translated into sets of testable hypotheses. This essay examines four issues which should facilitate the development of such hypotheses: (a) definitions of neuromotor synergies, (b) criteria for recognizing and comparing synergies in automatic and intentional actions, (c) problems in representing systems of synergies, and (d) models for generating intentional actions from sets of neuromotor synergies. Limitations of, and support for the neuromotor synergy hypothesis are discussed, both in general and for the specific cases of postural synergies and cervico-spinal reflexes. Although current data do not provide conclusive support for or against the neuromotor synergy hypothesis, the problem can be formulated in ways open to experimental investigation.

Journal Article↗

PubMed1996

Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test.

An in vitro method of detecting synergy which is simple to perform, accurate, and reproducible and has the potential for clinical extrapolation is desirable. Time-kill and checkerboard methods are the most widely used techniques to assess synergy but are time-consuming and labor-intensive. The Epsilometer test (E test), a less technically demanding test, has not been well studied for synergy testing. We performed synergy testing of Escherichia coli ATCC 35218, Enterobacter cloacae ATCC 23355, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 29213 with various combinations of cefepime or ceftazidime with tobramycin or ciprofloxacin using time-kill, checkerboard, and E test techniques. Time-kill testing was performed against each organism alone and in combinations at one-fourth times the MIC (1/4 x MIC) and 2 x MIC. With checkerboard tests, the same combinations were studied at concentrations ranging from 1/32 x to 4 x MIC. Standard definitions for synergy, indifference, and antagonism were utilized. E test strips were crossed at a 90 degree angle so the scales met at the MIC of each drug alone, and the fractional inhibitory concentrations index was calculated on the basis of the resultant zone on inhibition. All antimicrobial combinations demonstrated some degree of synergy against the test organisms, and antagonism was infrequent. Agreement with time-kill testing ranged from 44 to 88% and 63 to 75% by the checkerboard and E test synergy methods, respectively. Despite each of these methods utilizing different conditions and endpoints, there was frequent agreement among the methods. Further comparisons of the E test synergy technique with the checkerboard and time-kill methods are warranted.

Bacteria↗

PubMed1994

Simple test of synergy between ampicillin and vancomycin for resistant strains of Enterococcus faecium.

The combination of ampicillin and vancomycin kills some but not all strains of ampicillin- and vancomycin-resistant Enterococcus faecium. We compared a simple test for synergy utilizing a commercially available microdilution susceptibility system with time-kill studies and determined acceptable breakpoints for this test for 20 strains of ampicillin- and vancomycin-resistant E. faecium. The combination of ampicillin and vancomycin was tested for synergy by time-kill, broth macrodilution, and broth microdilution procedures. Repeat testing of isolates by macro- and microdilution synergy methods yielded MICs that were within one twofold dilution of each other for both intra- and intertest comparisons. Synergy was always detected by time-kill studies when the MIC of ampicillin in the combination synergy screen was < or = 8 micrograms/ml in the presence of vancomycin. No synergy was detected when the MIC was > 16 micrograms/ml in the combination microdilution synergy screen. The determination of the synergy by the broth microdilution procedure appears to be simple, convenient, and accurate.

Ampicillin↗

PubMed1989

Lack of in vitro synergy between etoposide and cis-diamminedichloroplatinum(II).

Claims of synergy between etoposide and cisplatin have been based upon preclinical in vivo murine P388 models or upon human clinical trials in tumors such as lung cancer. Such in vivo studies are useful in exploring therapeutic synergy, i.e., an improved therapeutic strategy. The term "synergy" in this context is sometimes, however, taken to imply greater than additive kill of tumor cells. Unfortunately, it is virtually impossible to document supra-additive tumor cell kill in vivo, since in vivo curves of therapeutic effect are not linear and drugs are therefore not additive with themselves. Therapeutic synergy may, in fact, occur when two drugs are merely additive (or even antagonistic) with regard to cytotoxicity if the drugs have nonoverlapping host toxicity. The demonstration of true supra-additive cell kill would imply an interaction of the two agents at a cellular level and would have profound implications for biochemical studies. In order to determine whether the reported therapeutic synergy of etoposide and cisplatin is due, in part, to supra-additive cell kill, we used an in vitro tetrazolium-based colorimetric assay for cytotoxicity (MTT assay) and an isobologram analysis to test combinations of the two drugs against four human small cell and four human non-small cell lung carcinoma lines. Using a rigorous test for in vitro synergy, we could not establish a greater than additive cytotoxic effect on our cell lines. It thus appears that the clinical synergy between etoposide and cisplatin is not due to a supra-additive effect at the cellular level. Our results have implications for a variety of fields in which claims of "synergy" often appear.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

[Contribution of cerebellar efferents to the organization of motor synergy].

The lack of coordination in cerebellar patients is due to deficits affecting both the programming and the execution of motor activity. The aspects of motor performance which are most severely affected are the chronology, the time course and the distribution of the activatory inputs to the muscles. The cerebellar control of motor synergies partly depends on the intrinsic organization of the cerebellar cortex, but interconnections between the cerebellum and the cortex, as well as the organization of the cerebello-spinal outputs are also involved. All these elements take part in different ways in the various aspects of motor synergy control. Depending on the type of sensory signals involved in the triggering of coordinations, different cortico-cerebello-cortical connections take part in their programming. Those synergies which are initiated by external sensory signals are triggered by inputs from the dentate and interposed nuclei and transmitted to parietal associative areas 5 and 7. The programming of the synergies induced by internal signals or motivational states involves projections from the dentate nucleus to prefrontal area 9 as well as to the supplementary motor (SMA) and premotor (PM) areas. The distribution of the cerebellar outputs to the muscles participating in motor synergies depends on the organization of the cerebellar circuits projecting to PM and M1 neurones at the origin of the descending pathways. The fastigial and dentate nuclei give off projections to the PM whereby they activate both axial and proximal muscles via bilateral reticulo-spinal pathways, and these nuclei are therefore responsible for synergies which provide for the necessary postural adjustments when limb movements are performed. When voluntary movements are to be performed, the cerebellar efferents from the three cerebellar nuclei to the motor cortex (M1) are able to trigger all the necessary synergies. Since the motor cortex can be subdivided into several representation areas dealing with elementary unidirectional movements performed by a single joint, activating the requisite coordinations requires particular patterns of cerebello-thalamocortical activation. With these networks, which can be said to constitute the morphological basis of motor synergies, several body representation cortical areas can be activated simultaneously. These networks seem to be partly set up before birth; but they may also be shaped during the early stages of life. They are still adaptable during adult-hood, and they can undergo synaptic and functional changes in response to the sensory constraints imposed by the environment.

Animals↗

PubMed2006

Anticipatory adjustments of multi-finger synergies in preparation for self-triggered perturbations.

We studied changes in multi-finger synergies associated with predictable and unpredictable force perturbations applied to a finger during a multi-finger constant total force production task. The main hypothesis was that indices of multi-finger synergies can show anticipatory changes in preparation for a predictable perturbation. Subjects sat in a chair and pressed on force sensors with the four fingers of the right hand. The task was to produce a constant level of total force. The fingers acted against loads that produced upward directed forces. The loads (applied either to the index or to the ring finger) could be disengaged either by the subject or by the experimenter. An index of finger co-variation, DeltaV was computed across sets of 12 trials at each time sample and for all tasks separately. During steady-state force production, all subjects showed positive DeltaV values corresponding to strong negative covariation among finger forces interpreted as a force-stabilizing synergy. Prior to self-triggered unloading, subjects showed an anticipatory drop in DeltaV that started 100-125 ms prior to the unloading time. Such early changes were absent in trials with experimenter-triggered unloading. After an unloading, subjects changed forces of both perturbed and unperturbed fingers and reached a new sharing pattern of the total force. In experimenter-triggered conditions, changes in the forces of unperturbed fingers could be seen as early as 120 ms following an unloading. The index DeltaV dropped following a perturbation and then recovered; the recovery occurred faster in self-triggered conditions. We conclude that humans can use feed-forward changes in multi-finger synergies (anticipatory synergy adjustments) in anticipation of a predictable perturbation. These changes may help avoid prolonged weakening of a multi-digit force-stabilizing synergy. We discuss a possibility that anticipatory postural adjustments may represent a particular case of the phenomenon of anticipatory synergy adjustments and suggest a hierarchical control scheme that incorporates a possibility of independent control over the output of a multi-element system and covariation patterns among outputs of its elements.

Adult↗

PubMed2006

Muscle synergies during voluntary body sway: combining across-trials and within-a-trial analyses.

We investigated co-varied changes in muscle activity during voluntary sway tasks that required a quick shift of the center of pressure (COP). We hypothesized that multi-muscle synergies (defined as task-specific covariation of elemental variables, muscle modes) stabilize a COP location in the anterior-posterior direction prior to a voluntary COP shift and that during the shift the synergies would weaken. Standing subjects performed two tasks, a cyclic COP shift over a range corresponding to 80% of the maximal amplitude of voluntary COP shift at 1 Hz and a unidirectional quick COP shift over the same nominal amplitude. The cyclic sway task was used to define muscle modes (M-modes, leg and trunk muscle groups with parallel scaling of muscle activation level within a group) and the relations between small changes in the magnitudes of M-modes [in the principal component analysis (PCA), the M-mode magnitudes are equivalent to PC scores] and COP shifts. A novel approach was used involving PCA applied to indices of muscle integrated activity measured both within a trial and across trials. The unidirectional sway task was performed in a self-paced (SP) manner and under a typical simple reaction time (RT) instruction. M-modes were also defined along trials at those tasks; they have been shown to be similar across tasks. Integrated indices of muscle activity in the SP-sway and RT-sway tasks were transformed into the M-modes. Variance in the M-mode space was partitioned into two components, one that did not affect the average value of COP shift (V (UCM)) and the other that did (V (ORT)). An index (DeltaV) corresponding to the normalized difference between V (UCM) and V (ORT) was computed. During steady-state posture, DeltaV was positive corresponding to most M-mode variance lying in a sub-space corresponding to a stable COP location across trials. Positive DeltaV values have been interpreted as reflecting a multi-M-mode synergy stabilizing the COP location. The magnitude of DeltaV was larger in SP trials than in RT trials. During voluntary COP shifts, the DeltaV magnitude dropped to zero or even became negative. We conclude that M-mode synergies stabilize COP location during quiet standing, while these synergies weaken or disappear during fast voluntary COP shifts. Under RT conditions, the COP stabilizing synergies were weaker supposedly to facilitate a quick COP shift without time for preparation. The suggested method of M-mode identification may potentially be applied to analysis of postural synergies in persons with impaired postural control such as elderly persons, persons with atypical development, or in the course of rehabilitation after an injury.

Adult↗

PubMed2003

Ras signaling and transcriptional synergy at a flexible Ets-1/Pit-1 composite DNA element is defined by the assembly of selective activation domains.

Pit-1 and Ets-1 binding to a composite element synergistically activates and targets Ras-mitogen-activated protein kinase signaling to the rat prolactin promoter. These transcriptional responses appear to depend on three molecular features: organization of the Ets-1/Pit-1 composite element, physical interaction of these two factors via the Pit-1 homeodomain (amino acids 199-291) and the Ets-1 regulatory III domain (amino acids 190-257), and assembly of their transcriptional activation domains (TADs). Here we show that the organization of the Ets-1/Pit-1 composite element tolerates significant flexibility with regard to Ras stimulation and synergy. Specifically, the putative monomeric Pit-1 binding site can be substituted with bona fide binding sites for either a Pit-1 monomer or dimer, and these sites tolerated a separation of 28 bp. Additionally, we show that the physical interaction of Ets-1 and Pit-1 is not required for Ras responsiveness or synergy because block mutations of the Pit-1 interaction surface in Ets-1, which reduced Ets-1/Pit-1 binding in vitro, did not significantly affect Ets-1 stimulation of Ras responsiveness or synergy. We also show differential use of distinct TAD subtypes and Pit-1 TAD subregions to mediate either synergy or Ras responsiveness. Specifically, TADs from Gal4, VP16, or Ets-2 regulatory III domain linked to Ets-1 DNA binding domain constructs restored synergy to these TAD/Ets-1 DNA binding domain fusions. Conversely, deletion of the defined Pit-1 TAD (amino acids 2-80) retained synergy, but not Ras responsiveness. Consequently, we further defined the Pit-1 amino-terminal TAD into region 1 (R1, amino acids 2-45) and region 2 (R2, amino acids 46-80). R1 appears to regulate basal and synergistic responses, whereas the Ras response was mapped to R2. In summary, Ras responsiveness and Pit-1/Ets-1 synergy are mediated through the assembly of distinct TADs at a flexible composite element, indicating that different mechanisms underlie these two transcriptional responses and that the Pit-1 R2 subregion represents a novel, tissue-specific Ras-responsive TAD.

Amino Acid Sequence↗

PubMed1986

Correlation of antibiotic synergy in vitro and in vivo: use of an animal model of neutropenic gram-negative sepsis.

The predictive value of in vitro studies of antibiotic interaction for clinical drug interactions is unclear. Five clinical isolates (two Klebsiella, two Pseudomonas aeruginosa, and one Serratia marcescens) were evaluated by the time-kill curve method for in vitro synergy between amikacin and imipenem. When we used the stringent definition of synergy of Hallander et al., no synergy was present for any study strain; however, when we used a more-conventional definition of synergy, these drugs interacted synergistically against all study strains. The results of these in vitro studies were correlated with in vivo interactions by using neutropenic infant rats injected ip with study organisms and given various treatment regimens. For 80% of the study strains, treatment of rats with amikacin and imipenem resulted in significantly greater survival than did therapy with either drug alone or than could be predicted by addition of survival rates achieved with either agent alone (P less than .005). In vitro studies predicted this in vivo synergy in 80% of the cases when the more-conventional definition of synergy was used, whereas they were not predictive when the more-stringent definition of synergy was used. This rat model of neutropenia and gram-negative sepsis may provide more insight into in vivo drug interactions than do current methods.

Agranulocytosis↗

PubMed2005

In vitro synergy of ciprofloxacin and gatifloxacin against ciprofloxacin-resistant Pseudomonas aeruginosa.

Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32 microg/ml, and for gatifloxacin they were >32 microg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P. aeruginosa isolates using a summation fractional inhibitory concentration of < or = 0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include P. aeruginosa ciprofloxacin efflux pump inhibition by gatifloxacin.

Anti-Bacterial Agents↗

PubMed1981

Methodological variation in antibiotic synergy tests against enterococci.

Thirty-two human isolates of enterococci were tested for antibiotic synergy by using penicillin and one of six aminoglycosides. Three methods were used: synergy screen, microdilution checkerboard, and time-kill curves. The synergy screen accurately predicted synergy for gentamicin-penicillin combinations, and this synergy was later confirmed by time-kill curves. The microdilution checkerboard method suffered from inherent variation, and agreement with time-kill curves ranged from 92% (twofold reduction in minimum inhibitory concentration) to 4.2% (fourfold reduction in minimum inhibitory concentration). We suggest that enterococci be screened for synergy (i.e., presence or absence of high-level resistance) by using the criterion of growth or no growth in the presence of 2,000 microgram of an aminoglycoside per ml. The microdilution checkerboard test for synergy is not recommended.

Aminoglycosides↗

PubMed2001

Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies.

Several reports have described the existence of synergy between neutralizing monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 (HIV-1). Synergy between human MAbs b12, 2G12, 2F5, and 4E10 in neutralization of primary isolates is of particular interest. Neutralization synergy of these MAbs, however, has not been studied extensively, and the mechanism of synergy remains unclear. We investigated neutralization synergy among this human antibody set by using the classical approach of titrating antibodies mixed at a fixed ratio as well as by an alternative, variable ratio approach in which the neutralization curve of one MAb is assessed in the presence and absence of a fixed, weakly neutralizing concentration of a second antibody. The advantage of this second approach is that it does not require mathematical analysis to establish synergy. No neutralization enhancement of any of the MAb combinations tested was detected for the T-cell-line-adapted molecular HIV-1 clone HxB2 using both assay formats. Studies of primary isolates (89.6, SF162, and JR-CSF) showed neutralization synergy which was relatively weak, with a maximum of two- to fourfold enhancement between antibody pairs, thereby increasing neutralization titers about 10-fold in triple and quadruple antibody combinations. Analysis of b12 and 2G12 binding to oligomeric envelope glycoprotein by using flow cytometry failed to demonstrate cooperativity in binding between these two antibodies. The mechanism by which these antibodies synergize is, therefore, not yet understood. The results lend some support to the notion that an HIV-1 vaccine that elicits moderate neutralizing antibodies to multiple epitopes may be more effective than hereto supposed, although considerable caution in extrapolating to a vaccine situation is required.

AIDS Vaccines↗

PubMed2004

A limited set of muscle synergies for force control during a postural task.

Recently developed computational techniques have been used to reduce muscle activation patterns of high complexity to a simple synergy organization and to bring new insights to the long-standing degrees of freedom problem in motor control. We used a nonnegative factorization approach to identify muscle synergies during postural responses in the cat and to examine the functional significance of such synergies for natural behaviors. We hypothesized that the simplification of neural control afforded by muscle synergies must be matched by a similar reduction in degrees of freedom at the biomechanical level. Electromyographic data were recorded from 8-15 hindlimb muscles of cats exposed to 16 directions of support surface translation. Results showed that as few as four synergies could account for >95% of the automatic postural response across all muscles and all directions. Each synergy was activated for a specific set of perturbation directions, and moreover, each was correlated with a unique vector of endpoint force under the limb. We suggest that, within the context of active balance control, postural synergies reflect a neural command signal that specifies endpoint force of a limb.

Animals↗

PubMed2004

Muscular and postural synergies of the human hand.

Because humans have limited ability to independently control the many joints of the hand, a wide variety of hand shapes can be characterized as a weighted combination of just two or three main patterns of covariation in joint rotations, or "postural synergies." The present study sought to align muscle synergies with these main postural synergies and to describe the form of membership of motor units in these postural/muscle synergies. Seventeen joint angles and the electromyographic (EMG) activities of several hand muscles (both intrinsic and extrinsic muscles) were recorded while human subjects held the hand statically in 52 specific shapes (i.e., shaping the hand around 26 commonly grasped objects or forming the 26 letter shapes of a manual alphabet). Principal-components analysis revealed several patterns of muscle synergy, some of which represented either coactivation of all hand muscles, or reciprocal patterns of activity (above and below average levels) in the intrinsic index finger and thumb muscles or (to a lesser extent) in the extrinsic four-tendoned extensor and flexor muscles. Single- and multiunit activity was generally a multimodal function of whole hand shape. This implies that motor-unit activation does not align with a single synergy; instead, motor units participate in multiple muscle synergies. Thus it appears that the organization of the global pattern of hand muscle activation is highly distributed. This organization mirrors the highly fractured somatotopy of cortical hand representations and may provide an ideal substrate for motor learning and recovery from injury.

Electromyography↗