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Previous research has shown that changes in shot difficulty may have rendered the hot-hand effect in basketball unobservable and are potentially a result of defensive adjustments. However, it has not been directly analysed whether strategic changes indeed take place in response to streakiness and whether they are effective with respect to winning games. The current work consists of an experimental study with 18 professional coaches and 20 players based on video sequences from National Basketball Association games, where the shown player displayed a streaky performance in half of the sequences. While coaches were asked to devise a defensive strategy after each viewed sequence, players had to assume the role of the shown player and decide whether to shoot or pass the ball. We find that coaches tended to increase the defensive pressure significantly more often on presumably hot players and thus make use of the hot-hand heuristic. Meanwhile, players chose to shoot more frequently in low-pressure and streaky situations but selected "pass" regardless of the previous performance when they faced increased defensive pressure. Assuming that a streaky player's performance is indeed elevated during hot phases, hot-hand behaviour can be considered adaptive in certain situations as it led hot players to pass instead of shoot.

The hot-hand phenomenon, according to which a player's performance is significantly elevated during certain phases relative to the expected performance based on the player's base rate, has left many researchers and fans in basketball puzzled: The vast majority of players, coaches and fans believe in its existence but statistical evidence supporting this belief has been scarce. It has frequently been argued that the hot hand in basketball is unobservable because of strategic adjustments and defensive interference of the opposing team. We use a dataset with novel metrics, such as the number of defenders and the defensive intensity for each shot attempt, which enable us to directly measure defensive pressure. First, we examine how the shooting percentage of NBA players changes relative to the attributes of each metric. We find that it is of lesser importance by how many defenders a player is guarded but that defensive intensity, e.g., whether a defender raises his hand when his opponent shoots, has a larger impact on shot difficulty. Second, we explore how the underlying metrics and shooting accuracy change as a function of streak length. Our results indicate that defensive pressure and shot difficulty increase (decrease) during hot (cold) streaks, so that defenders seem to behave according to the hot-hand belief and try to force hot players into more difficult shots. However, we find that shooting percentages of presumably hot players do not increase and that shooting performance is not related to streakiness, so that the defenders' hot-hand behavior cannot be considered ecologically rational. Therefore, we are unable to find evidence in favor of the hot-hand effect even when accounting for defensive pressure.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI-based 3D model of the sheep's brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheep's sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheep's sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks., (© 2014 Wiley Periodicals, Inc.)

Purpose: Recent evidence of the hot hand in sport-where success breeds success in a positive recency of successful shots, for instance-indicates that this pattern does not actually exist. Yet the belief persists. We used 2 studies to explore the effects of framing on the hot hand belief in sport. We looked at the effect of sport experience and task on the perception of baseball pitch behavior as well as the hot hand belief and free-throw behavior in basketball., Method: Study 1 asked participants to designate outcomes with different alternation rates as the result of baseball pitches or coin tosses. Study 2 examined basketball free-throw behavior and measured predicted success before each shot as well as general belief in the hot hand pattern., Results: The results of Study 1 illustrate that experience and stimulus alternation rates influence the perception of chance in human performance tasks. Study 2 shows that physically performing an act and making judgments are related. Specifically, beliefs were related to overall performance, with more successful shooters showing greater belief in the hot hand and greater predicted success for upcoming shots., Conclusions: Both of these studies highlight that the hot hand belief is influenced by framing, which leads to instability and situational contingencies. We show the specific effects of framing using accumulated experience of the individual with the sport and knowledge of its structure and specific experience with sport actions (basketball shots) prior to judgments.

Background and Aims: Mental training has the potential to enhance motor performance and behavior in older adults. Yet several studies have revealed age-related alteration of motor imagery (MI) ability, suggesting that mental training is not applicable for older adults. The purpose of the present study was to estimate MI performance in older adults, taking into account task requirements., Methods: MI performance of 20 older (mean age 70.75 ± 3.68 years) and 22 younger (mean age 24.31 ± 1.25 years) adults was estimated with the mental chronometry paradigm from the first-person perspective. Participants completed four walking tasks with different requirements, walking (A) in a straight line; (B) with two changes of direction; (C) on uneven ground; and (D) while additionally flipping switches. Path length and width were constant across tasks. MI ability was also measured with the Controllability of Motor Imagery Test, in which body parts have to be controlled and manipulated mentally. In addition, participants reported self-rated clarity of their MI in both tests after each trial., Results: Our data suggest no generalized alteration in MI of walking with different task requirements among older adults. A significant Age × Condition × Task interaction emerged, but this result could not be attributed to a specific task requirement in post-hoc tests. For controllability of MI, older adults showed alterations in imagining body postures. These results showed dissociation with the self-rated clarity in both tests., Conclusion: The present findings suggest that older adults show no age-related alterations in MI for familiar movements. Mental Training of familiar movements could therefore be feasible for older adults and enables promising intervention strategies.

Expertise is characterized by fast decision-making which is highly adaptive to new situations. Here we propose that athletes use a toolbox of heuristics which they develop on their route to expertise. The development of heuristics occurs within the context of the athletes' natural abilities, past experiences, developed skills, and situational context, but does not pertain to any of these factors separately. This is a novel approach because it integrates separate factors into a comprehensive heuristic description. The novelty of this approach lies within the integration of separate factors determining expertise into a comprehensive heuristic description. It is our contention that talent identification methods and talent development models should therefore be geared toward the assessment and development of specific heuristics. Specifically, in addition to identifying and developing separate natural abilities and skills as per usual, heuristics should be identified and developed. The application of heuristics to talent and expertise models can bring the field one step away from dichotomized models of nature and nurture toward a comprehensive approach to the route to expertise.

The aims of this study were to examine the influence of salivary cortisol on tennis serve performance in a controlled setting and to investigate if cortisol predicts unique variance in performance beyond a subjective anxiety measure (i.e., Competitive State Anxiety Inventory-2 [CSAI-2]). Twenty-three tennis players performed two series of second tennis serves separated by an anxiety induction (i.e., arithmetic task). Cortisol was assessed six times during the experiment. Results show that cortisol response and a drop in serving performance are positively correlated (r=.68, p<.001). Cortisol also explains unique variance in performance (i.e., 19%) beyond CSAI-2 measures. Thus, considering cortisol measurements seems warranted in future research aimed at understanding performance., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In decision-making research, one important aspect of real-life decisions has so far been neglected: the mood of the decision maker when generating options. The authors tested the use of the take-the-first (TTF) heuristic and extended the TTF model to understand how mood influences the option-generation process of individuals in two studies, the first using a between-subjects design (30 nonexperts, 30 near-experts, and 30 experts) and the second conceptually replicating the first using a within-subject design (30 nonexperts). Participants took part in an experimental option-generation task, with 31 three-dimensional videos of choices in team handball. Three moods were elicited: positive, neutral, and negative. The findings (a) replicate previous results concerning TTF and (b) show that the option-generation process was associated with the physiological component of mood, supporting the neurovisceral integration model. The extension of TTF to processing emotional factors is an important step forward in explaining fast choices in real-life situations.

Visually guided tracking paradigms can provide insight into the adaptability of motor control strategies. We argue that the question of whether a sensorimotor process, or its absence, is beneficial or detrimental for performance is one that needs to be answered relative to the sensory cues available in the environment and the given task constraints. In this paper, we describe how and when environmental cues have task-dependent benefits. We used a new pursuit-tracking paradigm and added, removed, or replaced cues within the same tracking task in either predictable or unpredictable environments to investigate the use and adaptability of different control strategies. Participants were invited to perform a tracking task over six blocks in six different conditions. Compared to a condition where both target and control cursor (cues) were visible, performance was maintained when a cue was added and decreased when a cue was removed. Our results show that participants only learned to use new cues if the old one was removed and the replacement was valid. This means that the sensorimotor system adapts only if forced to do so instead of constantly exploiting optimization strategies.

This paper focuses on a model comparison to explain choices based on gaze behavior via simulation procedures. We tested two classes of models, a parallel constraint satisfaction (PCS) artificial neuronal network model and an accumulator model in a handball decision-making task from a lab experiment. Both models predict action in an option-generation task in which options can be chosen from the perspective of a playmaker in handball (i.e., passing to another player or shooting at the goal). Model simulations are based on a dataset of generated options together with gaze behavior measurements from 74 expert handball players for 22 pieces of video footage. We implemented both classes of models as deterministic vs. probabilistic models including and excluding fitted parameters. Results indicated that both classes of models can fit and predict participants' initially generated options based on gaze behavior data, and that overall, the classes of models performed about equally well. Early fixations were thereby particularly predictive for choices. We conclude that the analyses of complex environments via network approaches can be successfully applied to the field of experts' decision making in sports and provide perspectives for further theoretical developments., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Integrins are transmembrane proteins regulating cellular shape, mobility and the cell cycle. A highly conserved signature motif in the cytoplasmic tail of the integrin alpha-subunit, KXGFFKR, plays a critical role in regulating integrin function. To date, six proteins have been identified that target this motif of the platelet-specific integrin alpha(IIb)beta(3). We employ peptide-affinity chromatography followed-up with LC-MS/MS analysis as well as protein chips to identify new potential regulators of integrin function in platelets and put them into their biological context using information from protein:protein interaction (PPI) databases. Totally, 44 platelet proteins bind with high affinity to an immobilized LAMWKVGFFKR-peptide. Of these, seven have been reported in the PPI literature as interactors with integrin alpha-subunits. 68 recombinant human proteins expressed on the protein chip specifically bind with high affinity to biotin-tagged alpha-integrin cytoplasmic peptides. Two of these proteins are also identified in the peptide-affinity experiments, one is also found in the PPI databases and a further one is present in the data to all three approaches. Finally, novel short linear interaction motifs are common to a number of proteins identified.

A synthetic cell-permeable peptide corresponding to the highly conserved alpha-integrin signature motif, Palmityl-K(989)VGFFKR(995) (Pal-FF), induces integrin activation and aggregation in human platelets. Systematic replacement of the F(992)-F(993) with amino acids of greater or lesser hydrophobicity to create Pal-KVGxxKR peptides demonstrate that hydrophobic amino acids (isoleucine, phenylalanine, tyrosine, tryptophan) are essential for agonist potency. In marked contrast, substitution with small and/or hydrophilic amino acids (glycine, alanine, serine) causes a switch in the biological activity resulting in inhibition of platelet aggregation, adhesion, ADP secretion, and thromboxane synthesis. These substituted, hydrophilic peptides are not true pharmacological antagonists, as they actively induce a phosphotyrosine signaling cascade in platelets. Singly substituted peptides (Pal-AF and Pal-FA) cause preferential retention of pro- or anti-thrombotic properties, respectively. Because the alpha-integrin signature motif is an established docking site for a number of diverse cytoplasmic proteins, we conclude that eliminating critical protein-protein interactions mediated through the hydrophobic amino acids, especially F(993), favors an anti-thrombotic pathway in platelets. Agents derived from the inhibitory peptides described in this study may represent a new therapeutic strategy for anti-platelet or anti-integrin drug development.

In different scientific disciplines, decision making is studied by examining how options are perceived or generated in isolated situations. In this chapter we explore the benefits of an interdisciplinary approach to understanding option perception within human behavior. As a consequence of the contributions from different disciplines, we present a framework that describes the bidirectional links between decision making, perception, and action. We will argue that, given their interdependency, the study of decision making profits greatly from a more integrated view of the situations it studies. The framework also illustrates how constraints may influence these bidirectional links. Finally, we use this framework to convey new ideas for experimental paradigms, data interpretation, and applications.

This concluding chapter is written as an exercise in evaluative and formative outcome assessment for the workshop that produced the individual content chapters in this edited volume (entitled Mind and motion: the bidirectional link between thought and action; 29-31 May 2008; Bielefeld, Germany). We go beyond simply summarizing and reiterating the academic progress that was made in each group that is presented in the group reports. Rather, we focus on the obstacles that we encountered along the way in hopes of recognizing what may impede future progress in the study of motor-cognitive links. In particular, we identified three key challenges that arose during our workshop discussions: the limitations of a reductionist tendency, the myopia associated with disciplinary biases, and the threats to inferential validity when dealing with mental phenomena. We offer prescriptive advice about how to overcome these limitations and provide a template for future interaction by interdisciplinary researchers who want to continue scientific research in this domain.

We previously identified proteins that bind with high affinity to a peptide corresponding to the cytoplasmic regulatory domain (KVGFFKR) of the platelet-specific integrin subunit alpha(IIb). These included a hypothetical protein termed HSPC238, recently renamed as RING finger protein, RN181. Here, we establish the presence of RN181 in human platelets by RT-PCR, Western blotting and mass spectrometry and confirm its affinity for the platelet integrin. We demonstrate that RN181 has ubiquitin E3 ligase activity and that all other components of the ubiquitination pathway are abundant in platelets, suggesting a novel link of integrin signal transduction pathways with ubiquitin-conjugation events.

To understand the regulation of integrin alpha(IIb)beta(3), a critical platelet adhesion molecule, we have developed a peptide affinity chromatography method using the known integrin regulatory motif, LAMWKVGFFKR. Using standard Fmoc chemistry, this peptide was synthesized onto a Toyopearl AF-Amino-650 M resin on a 6-aminohexanoic acid (Ahx) linker. Peptide density was controlled by acetylation of 83% of the Ahx amino groups. Four recombinant human proteins (CIB1, PP1, ICln and RN181), previously identified as binding to this integrin regulatory motif, were specifically retained by the column containing the integrin peptide but not by a column presenting an irrelevant peptide. Hemoglobin, creatine kinase, bovine serum albumin, fibrinogen and alpha-tubulin failed to bind under the chosen conditions. Immunodetection methods confirmed the binding of endogenous platelet proteins, including CIB1, PP1, ICln RN181, AUP-1 and beta3-integrin, from a detergent-free platelet lysate. Thus, we describe a reproducible method that facilitates the reliable extraction of specific integrin-binding proteins from complex biological matrices. This methodology may enable the sensitive and specific identification of proteins that interact with linear, membrane-proximal peptide motifs such as the integrin regulatory motif LAMWKVGFFKR.

When ranking two alternatives by some criteria and only one of the alternatives is recognized, participants overwhelmingly adopt the strategy, termed the recognition heuristic (RH), of choosing the recognized alternative. Understanding the neural correlates underlying decisions that follow the RH could help determine whether people make judgments about the RH's applicability or simply choose the recognized alternative. We measured brain activity by using functional magnetic resonance imaging while participants indicated which of two cities they thought was larger (Experiment 1) or which city they recognized (Experiment 2). In Experiment 1, increased activation was observed within the anterior frontomedian cortex (aFMC), precuneus, and retrosplenial cortex when participants followed the RH compared to when they did not. Experiment 2 revealed that RH decisional processes cannot be reduced to recognition memory processes. As the aFMC has previously been associated with self-referential judgments, we conclude that RH decisional processes involve an assessment about the applicability of the RH.

Training methods in sport usually focus on improving either technical or tactical aspects of performance, ignoring the fact that successful performance requires the athlete to simultaneously decide what movement to perform and how it should be executed. Young elite table tennis players were trained, in a first phase, to improve their forehand and backhand movements and, in a second phase, to make a tactical switch between forehand and backhand movements. Half of the players took part in behavioral training focusing on how to perform the required movements, whereas half received additional video feedback about their technical and tactical performance (decision training). The results indicate that improvements of how decisions (techniques) and what decisions (tactics) can occur as a consequence of combining technical and tactical training. These results were stable in delayed Post-test analyses of competitive matches. It was concluded that a combination of both technical and tactical training is beneficial to elite table tennis performers, particularly during early seasonal training programs.

Motion is often thought of as the result of perceptual and higher cognitive processes. Although this idea has been investigated in myriad ways, the understanding of how movements tune cognitive processes is still in its infancy. The present study examined the nonaffective tuning of movements (arm extension and arm flexion) on heuristic and systematic processes. In a departure from recent cognitive tuning models, a model was derived that defines the tuning effect based on the movement goal and not on the movement position. In the experiment, participants moved toward an extension or flexion position with a movement goal which connected the movement with either an avoidance or an approach function. Analysis indicated that cognitive tuning is a product of the movement goal rather than the movement position. Implications for models of motor control as well as for cognitive tuning models are presented.

Non-invasive techniques such as neuroimaging and event-related potential (ERP) methods have dramatically enhanced our understanding of the human brain. According to the requirements of the applied method, it is useful to simplify tasks for methodological reasons. In the present study we tested whether ERP measures are also suitable for analyzing complex tasks. In order to do this, we developed an analysis strategy based on the post hoc analysis of the behavioural data. We applied this method to a pursuit-tracking task of 25 s trial duration, consisting of repeated and non-repeated waveforms, where subjects had to track a target cross with a mouse-controlled cursor cross. An EEG was recorded from 62 channels. Response-locked ERPs were computed for two types of error correction: the correction of errors induced externally by the change of target direction and of internal errors generated by the subject itself. We found several ERP components that could be assigned to different feedback and feedforward controlled processing steps in the frontoparietal circuitry underlying visuomotor control, such as movement planning, movement execution (motor potential), reafferent activity, visuospatial analysis, and attentional (P300) processes. Our results support newer models that propose a role for the posterior parietal cortex in integrating multimodal sensory information. In addition, fast (about 180 ms and probably facilitated by anticipation) and slow (about 230-260 ms) error corrections could be differentiated by the time course of ERP activity. Our results show that complex (motor) tasks can be investigated with ERPs. This opens fruitful perspectives for future research on motor control in an ecological setting.

The goal of this article is to explain empirical risk-taking behavior in sports from an individual cognitive modeling perspective. A basketball task was used in which participants viewed four video options that varied in the degree of associated risk. The participants were independently classified by scores on the Questionnaire for Assessing Prospective Action Orientation and State Orientation in Success, Failure, and Planning Situations as action-oriented or state-oriented decision makers. The results of the experiment show that action-oriented players shoot faster and more often to the basket and that state-oriented players prefer to pass to a playmaker more often. Four versions of a computational model of decision making, Decision Field Theory, were compared to evaluate whether behavioral differences depend on the focus of attention, the initial preferences, threshold values, or an approach-avoidance interpretation of the task. Different starting preferences explained individual choices and decision times most accurately. Risk taking in basketball shooting behavior can be best explained by different preferences for starting values for risky and safe options caused by different levels of action orientation.

Background: A variety of cytokines, mediators, activators, growth factors and other products are simultaneously released into circulation with the activation of the cellular immune system during rejection or infection. The secretion of these biochemical markers potentiates the immunological events associated with these processes. Among other things some cytokines demonstrate regulatory effects on the expression of endothelial cell adhesion molecules., Method: Endothelial cells are detached by trypsinisation and adhesion molecule expression is assessed by means of flow cytometry. Fluorescence-conjugated mouse monoclonal antibodies directed against VCAM-1, ICAM-1, PECAM-1, CD34, E- and P-selectin are used., Results: The combined application of different cytokines synergistically evokes P-selectin expression after a chosen incubation period of 16 h, while under single cytokine treatment P-selectin induction is not observed. Co-stimulation with TNF-alpha and a second cytokine reduces its influence on E-selectin. IL-1 beta/IFN-gamma lead to E-selectin levels higher than those under treatment with one of the both alone. Concomitant incubation with all cytokines synergistically down-regulates PECAM-1 referred to each cytokine alone., Conclusion: Our investigations in some cases clearly demonstrate that the combination of a second cytokine with TNF-alpha, IL-1 beta or IFN-gamma can either synergistically or antagonistically modulate the expression of adhesion molecules on HUVECs.

Background: Mycophenolic acid selectively inhibits inosine 5'-monophosphate dehydrogenase leading to a shortage of guanosine nucleotides. Since GTP is required for the synthesis of glycoproteins, this immunosuppressive drug also influences the production of several cell adhesion molecules., Method: Soluble endothelial cell adhesion molecules released into cell culture supernatants after an incubation period of 16 h are assessed via a standard ELISA procedure applying test kits for E-selectin, VCAM-1 and ICAM-1., Results: Treatment with TNF-alpha leads to the induction of E-selectin and causes a significant increase in VCAM-1 and ICAM-1 content in the supernatant in relation to the level of unstimulated cells. Due to the inhibitory effects of MPA-applied either alone or in combination with cyclosporin A and prednisolone-sE-selectin is significantly reduced and sVCAM-1 is slightly but not significantly decreased, whereas sICAM-1 levels remain unchanged., Conclusions: We demonstrate that the influence of MPA on endothelial cell adhesion molecules can readily be determined via ELISA. The results indicate that the immunosuppression by MPA is also achieved by slightly reducing the expression and consequent release of E-selectin, a pivotal molecule in the first step of leucocyte-endothelial interactions.

Background: Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyses the oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP). Thus, this enzyme plays an important role in the rate-limiting step of the de novo guanine nucleotide biosynthesis, making it a potent target for immunosuppressive drugs. Mycophenolic acid (MPA) is the most potent and specific inhibitor of IMPDH., Method: IMPDH activity is determined via evaluation of XMP formation and the inhibitory influence of MPA in human peripheral blood mononuclear cells (PBMCs) is assessed by means of high-performance liquid chromatography (HPLC). For this objective, we have optimised a method based on solvent-generated ion exchange chromatography by cautiously varying mobile phase parameters., Results: The optimised method renders it possible to separate 18 analytes in 54 min in a single isocratic experiment and to measure the IMPDH activity in the lysate of human PBMCs in dependence on incubation time, substrate, co-substrate and inhibitor concentrations. In this way, we have determined the Michaelis-Menten constants K(M) and V(max) for IMP and beta-NAD+ and the inhibitor constant K(i) for MPA., Conclusions: The chromatographic method presented in this report allows a rapid, reliable and reproducible quantification of IMPDH activity in PBMCs and therefore represents an attractive tool for the pharmacodynamic monitoring of the effects of MPA in patients under immunosuppressive therapy.

Background: Among the different factors playing crucial roles in endothelial cell activation, cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been reported to demonstrate profound effects on this cell type. It has been shown that the increased release of IFN-alpha/gamma and TNF-alpha causes structural and functional modulations of the endothelial cell. These cytokines participate in the recruitment and activation of the immune system. CsA is an immunosuppressive drug that is necessary at high levels in human recipients of vascularised xenografts. This drug could contribute to a prolonged graft survival by modulation of endothelial cell activation., Methods: The present study deals with the effects of cyclosporin A on adhesion molecule expression (i.e. ICAM-1, VCAM-1, E-selectin, P-selectin, PECAM-1 and the L-selectin ligand CD 34) on the surface of cytokine stimulated HUVECs. The in vitro model described herein mimics the stimulation of endothelial cells by cytokines as seen during inflammatory processes after transplantation. Therefore, HUVECs were activated either with TNF-alpha, IL-1beta or with a cytokine mixture consisting of those stimulants present at an elevated level in sera of patients during allograft rejection (i.e. IL-1beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma)., Results: The results obtained show that the immunosuppression of CsA is not only achieved by inhibiting lymphocyte proliferation, but also by decreasing the expression of adhesion molecules on endothelial cells, which are the first target of the cellular rejection process., Conclusion: Co-incubation of stimulated endothelial cells with a final CsA concentration of 5 microg/ml revealed a significant down-regulating influence on the surface expression of E-selectin and VCAM-1.