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Although the hand is an important organ in interpersonal interactions, focusing on this body part explicitly is less common in daily life compared with the face. We investigated (i) whether a person&rsquo, s recognition of their own hand is different from their recognition of another person&rsquo, s hand (i.e., self hand vs. other&rsquo, s hand) and (ii) whether a close social relationship affects hand recognition (i.e., a partner&rsquo, s hand vs. an unknown person&rsquo, s hand). For this aim, we ran an experiment in which participants took part in one of two discrimination tasks: (i) a self&ndash, others discrimination task or (ii) a partner/unknown opposite-sex person discrimination task. In these tasks, participants were presented with a hand image and asked to select one of two responses, self (partner) or other (unknown persons), as quickly and accurately as possible. We manipulated hand ownership (self (partner)/other(unknown person)), hand image laterality (right/left), and visual perspective of hand image (upright/upside-down). A main effect of hand ownership in both tasks (i.e., self vs. other and partner vs. unknown person) was found, indicating longer reaction times for self and partner images. The results suggest that close social relationships modulate hand recognition&mdash, namely, &ldquo, self-expansion&rdquo, to a romantic partner could occur at explicit visual hand recognition.

Eye movements toward sequentially presented face images with or without gaze cues were recorded to investigate whether those with ASD, in comparison to their typically developing (TD) peers, could prospectively perform the task according to gaze cues. Line-drawn face images were sequentially presented for one second each on a laptop PC display, and the face images shifted from side-to-side and up-and-down. In the gaze cue condition, the gaze of the face image was directed to the position where the next face would be presented. Although the participants with ASD looked less at the eye area of the face image than their TD peers, they could perform comparable smooth gaze shift to the gaze cue of the face image in the gaze cue condition. This appropriate gaze shift in the ASD group was more evident in the second half of trials in than in the first half, as revealed by the mean proportion of fixation time in the eye area to valid gaze data in the early phase (during face image presentation) and the time to first fixation on the eye area. These results suggest that individuals with ASD may benefit from the short-period trial experiment by enhancing the usage of gaze cue.

Objective Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (Af), but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes. Methods A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer-related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion-weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer. Results Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0 μg/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients. Conclusions We may differentiate cancer-associated AMEI from Af using a D-dimer level ≥ 2.0 μg/mL, which does not decrease during the sub-acute phase.

Although most patients with Parkinson's disease (PD) show decreased cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, some exhibit normal uptake. We evaluated the clinical characteristics of such patients.We enrolled 154 non-demented patients showing parkinsonism with normal cardiac MIBG uptake and had been clinically followed up during 29.9 ± 27.6 months. We defined the patients who did not fit the exclusion criteria for PD and demonstrated ≥ 30% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score after anti-Parkinson agent administration as probable PD. We compared clinical characteristics and the cardiac MIBG heart-to-mediastinum (H/M) ratio between the probable PD group (N=37) and other groups (N=117).The probable PD group showed significantly higher UPDRS motor scores and greater incidence of tremor/rigidity than those of other groups. In addition, they showed a significantly lower cardiac MIBG H/M ratio in the delayed phase (delayed, p0.0001). Washout-rate (WR) was significantly higher in probable PD cases (p0.0001). Among 16 probable PD patients undergoing serial cardiac MIBG scintigraphy, the delayed phase cardiac MIBG H/M ratio showed a significant decrease and WR significantly increased during follow-up periods.An increase in WR and lower delayed phase cardiac MIBG uptake were found to be characteristics of such patients.

Pointing is one of the communicative actions that infants acquire during their first year of life. Based on a hypothesis that early pointing is triggered by emergent reaching behavior toward objects placed at out‐of‐reach distances, we proposed a neural network model that acquires reaching without explicit representation of ‘targets’. The proposed model controls a two‐joint arm in a horizontal plane, and it learns a loop of internal forward and inverse transformations; the former predicts the visual feedback of hand position and the latter generates motor commands from the visual input through random generation of the motor commands. In the proposed model, the motor output and visual input were represented by broadly tuned neural units. Even though explicit ‘targets’ were not presented during learning, the simulation successfully generated reaching toward visually presented objects at within‐reach and out‐of‐reach distances.

Our previous study (Hum Mov Sci 25:349-371, 2006) investigated whether and how online vision in the early phase of movement influences the control of reach-to-grasp movements (movement duration: approximately 1000 ms). We used liquid-crystal shutter goggles to manipulate the duration of available online vision during the movement and specified that online vision during the early phase influences grasping movements. The current study examined the effect of online early phase vision on the grip configuration according to the movement duration and compared it between two different movement durations (approximately 500 and 1000 ms). We found that non-availability of early phase online vision affected the grip configuration (i.e., inducing a larger peak grip aperture) even in the shorter movement duration. The influential period for online vision for grasping control shifts to an earlier time when movement time is shorter (i.e., from approximately 214 to 106 ms after movement onset), indicating a flexible mechanism for grip configuration according to the movement duration and the available online vision.

Clioquinol is considered to be a causative agent of subacute myelo-optico neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore the further mechanism of neuronal damage by clioquinol, we evaluated the acetylation status of histones in PC12 cells. Clioquinol reduced the level of histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A upregulated acetylated histones and prevented the neuronal cell damage caused by clioquinol. In addition, treatment with HDAC inhibitor decreased neurite retraction and restored the inhibition of NGF-induced Trk autophosphorylation by clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol. Clioquinol is now used as a potential medicine for malignancies and neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate medicine for the prevention of its side effects on neuronal cells.

Following the princeps investigations of Marc Jeannerod on action–perception, specifically, goal-directed movement, this review article addresses visual and non-visual processes involved in guiding the hand in reaching or grasping tasks. The contributions of different sources of correction of ongoing movements are considered; these include visual feedback of the hand, as well as the often-neglected but important spatial updating and sharpening of goal localization following gaze-saccade orientation. The existence of an automatic online process guiding limb trajectory toward its goal is highlighted by a series of princeps experiments of goal-directed pointing movements. We then review psychophysical, electrophysiological, neuroimaging and clinical studies that have explored the properties of these automatic corrective mechanisms and their neural bases, and established their generality. Finally, the functional significance of automatic corrective mechanisms–referred to as motor flexibility–and their potential use in rehabilitation are discussed.

The aim of this study was to investigate the role of online vision of a target object and the participant’s moving hand in the early phase of reach-to-grasp movements. We designed an experiment that separately manipulated the visibility of a moving hand and the target object by using two liquid crystal shutter plates placed in the same horizontal plane (25 cm above the experimental table). When target view was available immediately after movement onset, the effect of hand view in the early phase of movement was very limited. The effect of hand view appeared when target view in the early phase of movement was not available. This was even the case for the condition where the temporal range of non-availability of target view after movement initiation was 150 ms. Therefore, online vision (of target and hand) for controlling grasping was utilized in a flexible fashion that depended on the visual environment.

In human reach-to-grasp movement, visual occlusion of a target object leads to a larger peak grip aperture compared to conditions where online vision is available. However, no previous computational and neural network models for reach-to-grasp movement explain the mechanism of this effect. We simulated the effect of online vision on the reach-to-grasp movement by proposing a computational control model based on the hypothesis that the grip aperture is controlled to compensate for both motor variability and sensory uncertainty. In this model, the aperture is formed to achieve a target aperture size that is sufficiently large to accommodate the actual target; it also includes a margin to ensure proper grasping despite sensory and motor variability. To this end, the model considers: (i) the variability of the grip aperture, which is predicted by the Kalman filter, and (ii) the uncertainty of the object size, which is affected by visual noise. Using this model, we simulated experiments in which the effect of the duration of visual occlusion was investigated. The simulation replicated the experimental result wherein the peak grip aperture increased when the target object was occluded, especially in the early phase of the movement. Both predicted motor variability and sensory uncertainty play important roles in the online visuomotor process responsible for grip aperture control.

A 74-year-old woman was hospitalized due to dysuria, weakness and dysesthesia of the lower extremities. She was in an immunosuppressed state following the administration of methylprednisolone therapy for idiopathic interstitial pneumonia. Cerebrospinal fluid and blood cultures were negative, and no infectious biomarkers were found. A gadolinium (Gd)-enhanced T1-weighted image of magnetic resonance imaging (MRI) revealed disseminated nodular lesions along the spinal cord. We suspected a diagnosis of seronegative deep mycosis and initiated anti-fungal therapy with voriconazole, which subsequently alleviated all of the patient's symptoms and MRI findings. Therefore, the presence of Gd-enhanced disseminated nodules on spinal MRI may be a good marker of deep meningeal mycosis.

Goal-directed prehension is a fundamental human skill and a form of interaction between actor and environment. We reviewed our studies on psychological experiments and computational modeling, examining how online vision affects the control of grasping (in particular, peak grip aperture). In the experiments, we investigated whether online vision in the early phase of movement affects the control of grasping (Experiment 1), and which kinds of visual sources (i.e., visual feedback of the limb/hand, the view of the target) are predominantly relied upon in this early movement phase (Experiment 2). These two experiments demonstrated that the view of the target in the rather early phase of movement is critical for grasping control. Next, we proposed a stochastic predictive control model using the Kalman filter for identifying the mechanism of the visuomotor process revealed in the experiment. The simulation results qualitatively replicated the experimental results, which showed the early phase availability of online vision and the priority of the view of the target on grasping control. Both studies suggest the importance of predictive control in human grasping.

The magnitude-redshift test is applied to cosmological models in extended theories of gravity containing extra terms in the Lagrangian which give rise to an evolving dark-energy component. Two classes of models are considered: one based on generalized scalar-tensor theory and the other on curvature corrections to the metric tensor. Results are compared to recent observational data of Type Ia supernovae. The predictions of both kinds of models may provide better fits to the data depending on dimensionless free parameters of order ∼ 0.01−0.1.

Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin ® ) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2 ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.

Models of the universe with a cosmological term which is introduced as a correction of the metric tensor field are studied. By revisiting with these models some of the conventional success, we infer that a model with a linear correction is a favourable candidate for a model of the universe. The cosmological constant and the flatness problems are examined in the model. There might be a possibility to solve the other cosmological problems only with the metric tensor field.

An exact class of solutions of the 5D vacuum Einstein field equations (EFEs) is obtained. The metric coefficients are found to be non-separable functions of time and the extra coordinate $l$ and the induced metric on $l$ = constant hypersurfaces has the form of a Friedmann-Robertson-Walker cosmology. The 5D manifold and 3D and 4D submanifolds are in general curved, which distinguishes this solution from previous ones in the literature. The singularity structure of the manifold is explored: some models in the class do not exhibit a big bang, while other exhibit a big bang and a big crunch. For the models with an initial singularity, the equation of state of the induced matter evolves from radiation like at early epochs to Milne-like at late times and the big bang manifests itself as a singular hypersurface in 5D. The projection of comoving 5D null geodesics onto the 4D submanifold is shown to be compatible with standard 4D comoving trajectories, while the expansion of 5D null congruences is shown to be in line with conventional notions of the Hubble expansion., Comment: 8 pages, in press in J. Math. Phys

The generalized scalar-tensor (GST) theory is modified. In the modified GST theory, the cosmological term ? is a function of the scalar field and of its time derivative {}2 as well. We obtain exact solutions for the scale factor, the scalar field and the cosmological term which evolves with a different dependence on time for each era of the universe. The cosmological `constant' and flatness problems are examined in the simple case of a flat universe.

The relationship between cosmological solutionsof five-dimensional Space-Time-Matter (STM) theory anda Generalized Scalar-Tensor (GST) theory is investigatedin which the cosmological term Lambda depends not only on a scalar field φ but also onits time derivative \(\dot \phi ^2 \).Identification of these solutions allows us to solve forthe functional form of the cosmological term, and mayhave relevance for the early Universe.

A 6D Space-Time-Mass-Charge (STMC) Theory is taken to see how far the physical properties of the 4D Space-Time Universe can be explained by the geometrical quantities of the extra dimensions. The equation of state for the macroscopic bodies is obtained, and the general properties of the electromagnetic field can be studied.

When performing reach-to-grasp movement, the fingers open wider than the size of the target object and then stop opening. The recorded peak grip aperture (PGA) is significantly larger when performing this action without vision during the movement than with vision, presumably due to an error margin that is retained in order to avoid a collision with the object. People can also pretend such prehension action based on an internal target representation (i.e., pantomimed prehension), and previous studies showed that the kinematic differences exist between natural and pantomimed prehension. These differences are regarded as a reflection of the respective information processing in the brain, namely, the dorsal and ventral streams. Pantomimed movements are thought to be mediated by the ventral stream. This implies that visual information during the movement, which is essential for the dorsal stream, has little effect on the kinematic properties of pantomimed prehension. We investigated whether the environment’s view affects pantomimed grasping; namely, whether the dorsal stream is involved in the execution of the pantomimed action. Participants initially gazed at a target object and then were subjected to a 3-second visual occlusion, during which time the experimenter removed the object. The participants were then required to pretend reach-to-grasp movements toward the location where the object had been presented. Two visual conditions (full vision and no vision) were imposed during the pantomimed prehension by manipulating shutter goggles. The PGA showed significant differences between the two visual conditions, whereas no significant difference was noted for terminal grip aperture, which was recorded at the movement end. This suggests an involvement of the dorsal stream in pantomimed action and implies that pantomimed prehension is a good probe for revealing the mechanism of interaction between the ventral and dorsal streams, which is also linked to embodied cognition.

It is shown that physical quantities in the 4D world such as density and pressure, and an equation of state for a gravitating spherically symmetric fluid, are given by the geometrical property of the fifth dimension of a spherically symmetric line-element in Wesson's 5D theory of gravity.

A simple vacuum cosmological solution that is a function ofct, Gm/c 2 andeG 1/2/C2 is obtained in the 6D space-time-mass-charge universe which is proposed by Wesson [1] with the introduction of the sixth coordinate of charge in order to obtain a unified theory of gravity and electromagnetism along the line of his original 5D space-time-mass universe [2]. It reduces to a similar solution to that of the radiation era in the 4D FRW universe through the compactifications of the extra dimensions. The trajectory of a “test particle” in the 6D universe is also studied by using the solution.

Our motor actions are sometimes not properly performed despite our having complete understanding of the environmental situation with a suitable action intention. In most cases, insufficient skill for motor control can explain the improper performance. A notable exception is the action of stepping onto a stopped escalator, which causes clumsy movements accompanied by an odd sensation. Previous studies have examined short-term sensorimotor adaptations to treadmills and moving sleds, but the relationship between the odd sensation and behavioral properties in a real stopped-escalator situation has never been examined. Understanding this unique action-perception linkage would help us to assess the brain function connecting automatic motor controls and the conscious awareness of action. Here we directly pose a question: Does the odd sensation emerge because of the unfamiliar motor behavior itself toward the irregular step-height of a stopped escalator or as a consequence of an automatic habitual motor program cued by the escalator itself. We compared the properties of motor behavior toward a stopped escalator (SE) with those toward moving escalator and toward a wooden stairs (WS) that mimicked the stopped escalator, and analyzed the subjective feeling of the odd sensation in the SE and WS conditions. The results show that moving escalator-specific motor actions emerged after participants had stepped onto the stopped escalator despite their full awareness that it was stopped, as if the motor behavior was guided by a “phantom” of a moving escalator. Additionally, statistical analysis reveals that postural forward sway that occurred after the stepping action is directly linked with the odd sensation. The results suggest a dissociation between conscious awareness and subconscious motor control: the former makes us perfectly aware of the current environmental situation, but the latter automatically emerges as a result of highly habituated visual input no matter how unsuitable the motor control is. This dissociation appears to yield an attribution conflict, resulting in the odd sensation.

Two experiments were conducted to investigate (1) during which phase of the movement vision is most critical for control, and (2) how vision of the target object and the participant’s moving limb affect the control of grasping during that movement phase. In Experiment 1, participants, wearing liquid crystal shutter goggles, reached for and grasped a cylinder with a diameter of 4 or 6 cm under a shutting paradigm (SP) and a re-opening paradigm (RP). In SP, the goggles closed (turned opaque) 0 ms, 150 ms, 350 ms, 500 ms, or 700 ms after movement onset, or remained open (transparent) during the prehension movements. In RP, the goggles closed immediately upon movement onset, and re-opened 0 ms (i.e., without initially shutting), 150 ms, 350 ms, 500 ms, or 700 ms after the initial shutting, or remained opaque throughout the prehension movements. The duration of the prehension movements was kept relatively constant across participants and trials at approximately 1100 ms, i.e., the duration of prehension movements typically observed in daily life. The location of the target object was constant during the entire experiment. The SP and RP paradigms were counter-balanced across participants, and the order of conditions within each session was randomized. The main findings were that peak grip aperture (PGA) in the 150 ms-shutting condition was significantly larger than in the 350 ms-shutting condition, and that PGA in the 350 ms-re-opening condition was significantly larger than in the 150 ms-re-opening condition. These results revealed that online vision between 150 ms and 350 ms was critical for grasp control on PGA in typical, daily-life-speeded prehension movements. Furthermore, the results obtained for the time after maximal deceleration (TAMD; movement duration − time to maximal deceleration) demonstrated that early-phase vision contributed to the temporal pattern of the later movement phases (i.e., TAMD). The results thus demonstrated that online vision in the early phase of movement is crucial for the control of grasping. In addition to the apparatus used in Experiment 1, two liquid shutter plates placed in the same horizontal plane (25 cm above the experimental table) were used in Experiment 2 to manipulate the visibility of the target and the participant’s moving limb. The plate closest to the participant altered vision of the limb/hand, while the more distant plate controlled vision of the object. The conditions were as follows: (1) both plates were open during movement (full vision condition); (2) both plates were closed 0, 150, or 350 ms following onset of arm movement (front-rear condition: FR); or (3) only the near plate closed 0, 150, or 350 ms following the onset of the arm movement (front condition: F). The results showed that shutting at 0 and 150 ms in the FR condition caused a significantly larger PGA, while the timing of shutting in the F condition had little influence on the PGA. These findings indicated that online vision, especially of the target object, during the early phase of prehension movements is critical to the control of grasping.

A generalized scalar-tensor theory is investigated whose cosmological term depends on both a scalar field and its time derivative. A correspondence with solutions of five-dimensional Space-Time-Matter theory is noted. Analytic solutions are found for the scale factor, scalar field and cosmological term. Models with free parameters of order unity are consistent with recent observational data and could be relevant to both the dark-matter and cosmological-"constant" problems., 13 pages

An accelerating flat universe with a variable cosmological term is obtained in the Robertson-Walker metric. The variable cosmological term is defined by the correction terms of the metric tensor field. Simple solutions of the scale factor and the cosmological term are shown. In this model of the universe, the magnitude-redshift relation is analytically studied to see if the model reproduces the tendency of the present observational data. The equation of state parameter $\gamma$ is touched., Comment: 7 pages

Previous studies demonstrated that human motor actions are not always monitored by perceptual awareness and that implicit motor control plays a key role in performing actions. In addition, appropriate evaluation of our own motor behavior is vital for human life. Here we combined a reaching task with a visual backward masking paradigm to induce an implicit motor response that is congruent or incongruent with the visual perception. We used this to investigate (i) how we evaluate such implicit motor response that could be inconsistent with perceptual awareness and (ii) the possible contributions of reaching error, external visual cues, and internal sensorimotor information to this evaluation. Participants were instructed, after each trial, to rate their own reaching performance on a 5-point scale (i.e., smooth – clumsy). They also needed to identify a color presented at a fixation point that could be changed just after the reaching start. The color was linked to the prime-mask congruency (i.e., congruent-green, incongruent-blue) in the practice phase, and then inconsistent pairs (congruent-blue or incongruent-green) were introduced in the test phase. We found early trajectory deviations induced by the invisible prime stimulus, and such implicit motor responses are significantly correlated with the action evaluation score. The results suggest the “conscious” action evaluation is properly monitoring online sensory outcomes derived by implicit motor control. Furthermore, statistical path analyses showed that internal sensorimotor information from the motor behavior modulated by the invisible prime was the predominant cue for the action evaluation, while the color-cue association learned in the practice phase in some cases biases the action evaluation in the test phase.

We theoretically investigate how the photoexcited states change across the phase boundary between the charge density wave (CDW) and the spin density wave (SDW) states in the one-dimensional (1D) and the two-dimensional (2D) Pariser–Parr–Pople models in the strong interaction case. In the 1D case, the CDW (singlet spin pair) droplet states dominate light absorption spectrum in the SDW (CDW) ground state region near the phase boundary. These photoexcited states exhibit crossover behavior across the phase boundary, that is, the density of the CDW region gradually increases across the phase boundary from the SDW to the CDW ground state region. On the contrary, in the 2D case, the bound holon–doublon (singlet spin) pair state dominates the light absorption spectrum, and the quantum fluctuations of the CDW or the singlet spin pair domain are negligible in the dominant photoexcited state even near the phase boundary. As a result, the transition occurs in the dominant photoexcited state at the ground state phase ...

A cosmological solution is obtained in a 5D “space-time-mass” cosmological model by applying a homogeneous and isotropic metric, whose tensorsg ij (i, j =0–4) are functions of both timet and massm, to the field equations in vacuum. It shows that in this theoryg 44of the fifth coordinate is contracted not only by special functional form oft as in the Kaluza-Klein theory but also by that ofm. This procedure realizes the universe which evolves into a conventional 4D radiation-dominated era from a 5D vacuum era.

The origin of matter and the nature of diagonalization are studied in the framework of 5D STM gravity theory with off-diagonal components in the metric tensor. The time of change of mass is presented with a simple cosmological solution and the 5D geodesic equations. In the special case, our solution can be compared to Chodos and Detweiler's (1982) procedure assuming that the metric possesses a spacelike Killing vector.

The geodesic equation in a viable 5D space-time-mass theory of gravity is calculated for the purpose of presenting quantities accessible to experiments and observations. Determining the values of the constants in the theory is left for future tests concerning the principle of equivalence. But qualitatively we can show that the five-velocity is a function of not only of time but also mass. And in general case a possible change of mass depends onm as well ast.

In order to study the origin of the fundamental constants and Dirac's large number, a cosmological solution in vacuum is presented in a seven-dimensional universe which is defined by adding extra three coordinates (e 2 G/c 4)1/2, (hG/c 3)1/2 and (Gm/c 2) to the four-dimensional spacetime coordinates. It has common features with Chodos-Detweiler's solution. The parameters appearing in this theory are estimated to meet the conditions required by the cosmological first-order phase transition and Dirac's large number hypothesis.