In this paper, a new piezoelectric dynamic balance regulator, which can be used in motorised spindle systems, is presented. The dynamic balancing adjustment mechanism is driven by an in-plane bending vibration from an annular piezoelectric stator excited by a high-frequency sinusoidal input voltage. This device has different construction, characteristics and operating principles than a conventional balance regulator. In this work, a dynamic model of the regulator is first developed using a detailed analytical method. Thereafter, MATLAB is employed to numerically simulate the relations between the dominant parameters and the characteristics of the regulator based on thedynamic model. Finally, experimental measurements are used to certify the validity of the dynamic model. Consequently, the mathematical model presented and analysed in this paper can be used as a tool for optimising the design of a piezoelectric dynamic balance regulator during steady state operation. These devices use the converse piezoelectric effect of piezoceramics and convert the ultrasonic vibration of the stator into linear or rotational motion in a rotor using the friction force. They inherently posses slow speed/high torque output, high holding torque and rapid response characteristics, all of which combine for the potential to be used as a precise and accurate positioning actuator. Because standing wave-type ultrasonic motors have the advantage of accurate positioning without feedback, a new idea is proposed in this paper, an ultrasonic piezoelectric dynamic balance regulator based on the basic principles of a standing wave-type ultrasonic motor. This regulator is the key component of an in situ dynamic balance regulators for motors in 1964, proposed that a balance block, whose radial position relative to the centre of rotation was under continuous adjustment by a worm gear mechanism, could be used to achieve in situ rotor balancing. In 1978, Van de Vegte modified the dynamic balance regulator to use a mass block driven by a motor to change the angular displacement relative to the attached rotating spindle. The electrical power for the driving motor was supplied by external brush contacts [et al. [et al. [There are many different types of dynamic balance regulators that have evolved over the years in the field of rotor balancing. Van de Vegte , who fircontacts ,3. Bisho [et al.  used a wIn this paper, a new type of piezoelectric dynamic balance regulator is introduced, which can overcome some of the disadvantages of existing dynamic balance regulators. As pointed out before, this regulator based on the basic principles of a standing wave-type ultrasonic motor, and combines features such as high driving torque at low rotational speed, high holding torque without an applied electric power, extremely low noise in operation, accurate positioning without feedback, simple mechanical design and rapid response. Because the regulator utilises the in-plane bending vibration mode of the piezoelectric stators to drive the rotor, a contact interface exists on the circumferential side face. This type of structure further minimises the regulator thickness and miniaturises the regulator.Meanwhile, because the regulator is driven with single-phase AC voltage, this type of drive mode simplifies the supply power and enhances the system reliability. Above all, a particularly attractive feature of the regulator is that it possesses high displacement resolution and can achieve control precision on the order of microns, thus it can achieve very high adjustment accuracy.The topic of this paper is to perform high-efficiency dynamic modelling and to optimise the key parameters of this regulator. Analytical, numerical and experimental methods have been employed in these investigations. For simplicity, the non-linear contact mechanics are studied under the assumption that the vibrational characteristics of the resonating structure are not affected by the contact process. This analysis process simplifies the investigations considerably and quite often results in a good description of the mechanism of motion for the regulator. For an experimental illustration of the theoretical and numerical results, a sample device was fabricated and characterised based on this mechanical analysis. The experimental results reported on here confirm the validity and applicability of the regulator structure and can be used for guidance in further optimisation of the regulator.In Section 2 of this paper, the overall structural characteristics and the operating principles of the piezoelectric dynamic balance regulator are described in detail. In Section 3, a dynamic analysis on the stator, the rotor, the friction layer and the stator-rotor contact model is performed, which permits the energy conversion characteristics of the regulator to be obtained. In Section 4, MATLAB is employed to numerically simulate the characteristics of the regulator based on the above mathematical model, and optimisation of core parameters for the regulator is conducted according to the simulation results. Afterwards, a prototype is fabricated using the optimised parameters, and its performance is tested experimentally. Comparing the experimental and simulated load torque/rotational speed relation for the regulator, the validity of the dynamic model is proven. Finally, conclusions and future research prospects are detailed in Section 5.2.There are two piezoelectric actuating devices installed in the regulator housing. Each device consists of a rotor and a piezoelectric stator with six driving teeth. The stator is fixed on the mounting surface of the regulator. The driving teeth on the stator press against the inner circumference of the rotor, which rotates in a groove on the mounting surface .The stator and the rotor are pre-tensioned in the radial direction to avoid an increase in the motor thickness during operations. Additionally, a counterweight block is installed on each rotor and rotates with the rotor. When the piezoelectric stator resonates in an in-plane bending vibration mode under high-frequency sinusoidal voltage excitation, the stator will act as a friction drive to move the rotor structure to the desired position to alter the balancing vector. The combined action of the two piezoelectric actuating devices creates a resultant balancing vector that achieves dynamic balance adjustment by controlling the positions of the two counterweight blocks. The dynamic balancing principle is shown in The piezoelectric stator consists of an annular elastic metal body with two annular piezoceramic discs bonded to the top and bottom. Six driving teeth are distributed equally around the outer circumference of the metal body. Each bi-directionally polarised piezoceramic disc has six uniformly polarised regions, as shown in Under the excitation of a single-phase sinusoidal voltage at a specific frequency, a single wavelength of a standing wave is induced in each pair of neighbouring regions on each piezoceramic disc; consequently, the composite piezoelectric stator is three wavelengths long in the circumferential direction. When three identical high-frequency sinusoidal electrical signals are applied to the two piezoceramic discs, respectively, using the metal body as one electrode and the unbonded surfaces of the two piezoceramic discs as the other electrode, each disc generates its own standing wave pattern according to its polarisation pattern. The two standing waves are in phase and can excite the composite piezoelectric stator to produce the desired in-plane bending vibration modes ,  and , respectively. Because the  mode can be excited at relatively low frequency and has greater level radial and circumferential displacement components than the other two modes, it is chosen as the operating vibrational mode of the regulator.i.e., the crests and troughs of the stator vibration waves. Consequently, the six driving teeth are placed on the outer circumference of the annular stator so that when the teeth contact the rotor, their radial displacement produces a positive radial pressure on the rotor. Simultaneously, the circumferential displacement of the teeth produces relative motion in the rotor, and the rotor is propelled by the contact friction between the teeth and the rotor. T, the time is t and the outer circumference of the stator and the six driving teeth are spread along the abscissa. In the first half of the vibration period, the three teeth  in the rising state act to propel the output rotor in a counter-clockwise direction during contact. In the second half of the vibration period, the other three teeth  act in the same driving role. Therefore, during continuous vibration, the six teeth act in two groups to alternately propel the rotor continuously in a counter-clockwise direction.In the in-plane bending vibration mode , each point on the outer circumference of the annular stator has both radial and circumferential motion components. The circumferential displacement is non-zero for all points, except those at extreme radial displacements, 3.the rotor is a rigid body;thefriction material is visco-elastic, its surface is smooth and the influence of surface roughness is neglected;the Coulomb friction law is valid at the contact interface between the stator and rotor; andthe regulator runs in steady state (the starting and stopping processes of the regulator are not considered).Based on motion analysis in the previous section, it is obvious that the stator intermittently contacts the rotor, so the actuation direction of the regulator is unique. The analysis includes a significant number of non-linear and uncertain factors, and the whole drive process is very complicated. To simplify the model, the following assumptions are made ,9:the r3.1.z-axis and the middle annular surface of the stator as the r-θ plane. The resultant radial and circumferential displacement functions, ru and θu, of the in-plane bending vibration mode of the annular stator structure are derived as follows [λ is Lamé's constant, μ is Poisson's ratio, E is Young's modulus, G is the shear modulus, ρ is the material density, ω is the resonant angular frequency, n is the number of the wave or nodal diameter of the in-plane vibration, A, B, C and D are coefficients determined by the boundary conditions of the annular plate structure and nJ and nY are Bessel functions of the first and second type of the n-th order, respectively. The annular stator is considered to be a laminated annular plate with clamped boundary conditions at the inner edge and free boundary conditions at the outer edge. The boundary conditions are adopted to derive the resonant frequency of the in-plane vibration mode of the piezoelectric stator and are as follows:a and bare the outer and inner radii of the annular stator structure, respectively, and rrT and rθT are the radial normal stress and tangential shearing stress, respectively. Substituting the displacement function in rf for the annular stator is:n,mα is the natural frequency constant of the annular plate, the subscript m represents the number of the nodal circle and n represents the number of the wave or nodal diameter. The ANSYS finite element software is used to analyse the corresponding modal shapes of the in-plane bending vibration of the piezoelectric stator, as shown in The displacement behaviour for the annular stator can be derived approximately using the analytical method for the in-plane vibration of the thin elastic plate . First,  follows :(1){ur=rmaxu and θmaxu are the maximum radial and circumferential displacements, respectively.In To simplify the analysis, an orthogonal coordinate system is set up, as shown in 1A and 0A are the positions of the root point with and without deformation, respectively. The variables 1B and 0B are the positions of the top particle with and without deformation, respectively. The variable α is the swing angle of the tooth, and Th is the length of the tooth. The deformed position1A is displaced from the initial position A by  when the piezoceramic stator is excited by a sinusoidal electric signal. The general expressions for the vertical deformation rw and the horizontal deformation θw of the top pointare given as Two points are employed to perform the dynamic analysis and are located at the root and top of the stator tooth, respectively . The variables α, the following approximations hold true:For small values of Accordingly, α can be given as:Additionally, the swing angle According to the above analysis, the vertical deflection of outer circumferential surface of the stator can be expressed as:Substituting θnu ≈ θ,nu and cosθnu ≈ 1, For sinθnusinnx ≪ cosnx, and For this case, According to 3.2.2O3. However, in this paper, a special hard composite material coating is proposed for the regulator, which is softer than the base material and has a high wear resistance and stable mechanical properties with respect to temperature and environmental changes. The composite material employs an epoxy resin as base material, MoS2 and Al2O3 as padding materials. The curing temperature is possessed at 80 °C.In the piezoelectric dynamic balance regulator, the high-frequency intermittent friction contact between the stator and the rotor is essential to generate the driving force. Tribological processes occurring in high-frequency friction contacts determine the torque-speed characteristics, lifetime and long-term behaviour of the regulator. The appropriate choice of materials for the stator-rotor interface is important in the design of the regulator. Until now, intermittent-contact type ultrasonic motors have successfully used hard contact materials such as AlCrw and the linear velocity in the y-direction of the top point can be derived as follows:If the contact mechanics are studied assuming that the vibration characteristics of the stator are not affected by the contact processes, deformation will be produced on the friction layer when the rotor is pressed against the stator. The intermittent contact condition is assumed during steady state, and thus, there is not a contact gap between the interface at the driving teeth and the friction layer. Therefore, the displacement in the y-direction at a point on the friction layer is equal to the y-direction displacement of the top point. The y-direction displacement Rω and Cθω are the angular velocities of the rotor and the friction layer, respectively.As mentioned above, the rotor is assumed to be a rigid body. Additionally, the friction layer solidifies directly on the inner circumferential surface of the rotor. Therefore, the angular velocity of the rotor is equal to the angular velocity of the friction layer:3.3.im is the quality of the point of the rotor, ir is the rotational radius of the point im and RJ is the sum of the inertia moments of the rotor.Because the friction layer is softer than the base material of the rotor, the contact deformation is limited to the friction layer region. Thus, the rotor can be seen as a rigid body rotating on a fixed axis, and the equation describing the rotational inertia of the rotor can be given as:The momentum equation for a rigid rotor rotating on a fixed axis is given as:DM is the driving torque from the stator and LM is the load torque.The dynamic differential equation describing the rotor used in this research is written as:3.4.NF between the stator and rotor consists of two parts; one is the pre-load force C0F between the stator and the rotor, and the other is generated by means of in-plane vibration waves from the piezoceramic stator. In this paper, we restrict our attention to the contact problem between the stator and the rotor. For simplicity, we assume that the in-plane vibration waves are generated by a suitable distributed force CNF acting on the stator [C0F and CNF are N/m.The mechanics of the stator-rotor contact for the regulator are complicated due to the many parameters that must be taken into account. For the case of the rotor being regarded as a rigid body and the motion of the stator is assumed independent of the contact conditions, a visco-elastic foundation model can be employed to describe the stator-rotor contact characteristics. In the proposed regulator, the normal contact resultant force e stator . The norCE and ϑC are the Young's modulus and the viscosity coefficient of the friction material, respectively. The variables σ(t) and ε(t) are the stress and the strain of the friction layer, respectively. Additionally, ε(t) can be given as:Ch is the thickness of the friction layer.To further simplify the analysis, the essential assumption that the distributed contact force locally depends only on the local deformation at the contact points is used. The Kelvin-Voigt constitutive equation is therefore used to describe the stress-strain relationship of the friction material and is given by:Cb, the normal contact force CNF(t) is obtained as:For a contact area with a width of Substituting Because the friction forces depend mainly on factors such as the coefficient of static/dynamic friction, and considering the forces and stresses at the interface between the stator and the rotor, the normal contact pressure and the relative motion of interfaces, two different types of “friction” should be distinguished ,13.Sf and in most cases Sf is proportional to the normal force NF:Sμ is the coefficient of static friction.The maximum tangential resisting force at the contact interface before sliding begins is called the maximum static friction force df, called the dynamic friction force, arises at the contact interface. In most cases, df is also proportional to the normal force NF:dμ is the coefficient of dynamic friction.Once relative motion between the stator and the rotor begins, a certain tangential resistance force STν and Rν are the linear velocities of the top point in the x-direction and the corresponding point on surface of the friction layer, respectively.At the contact interface, while the linear velocity of the points on top of the driving teeth are greater than the corresponding points on the surface of the friction layer, the rotor is driven by the stator, and it can be thought that the friction force creates positive work, as shown in DM can be therefore calculated as:pr is the inner radius of rotor.Because the piezoelectric stator has six drive teeth and makes use of only three teeth to drive the rotor, according to the Coulomb friction law, the driving torque 3.5.A common feature of all piezoelectric actuators is their two-stage energy conversion process. In the first stage, the piezoelectric elements convert electric power energy to mechanical vibration power by the piezoelectric ceramics employed in the stator to induce standing waves in the stator at frequencies in the ultrasonic range. In the second stage, the wave energy in the stator is transferred to the rotor by means of the friction contact force between them. The energy conversion efficiency of the second stage is discussed in detail in this paper. Because the intermittent contact between the stator and the rotor is cyclical, it is possible to choose a contact cycle to analyse the energy conversion characteristics . The powCL is the length of the contact area between a stator tooth and the rotor.The frictional losses at the interfaces are:SC is the equivalent damping coefficient of the friction material.The energy dissipation from damping in the friction layer is:Finally, the conversion efficiency of the interface can be given by:4.4.1.In the proposed research on the piezoelectric dynamic balance regulator, the qualitative relationships between the structural parameters and the energy conversion characteristics must be determined. Therefore, MATLAB is employed to numerically simulate characteristics of the regulator based on the above mathematical model. The model parameters are found in outP is the output power and (lossP + Pdiss) as a whole is the loss power.When some parameters are analysed, they do not use the values from 4.1.1.The coefficient of dynamic friction is one of the most important properties of the friction material, and it is necessary to analyse its influence on the output characteristics of the regulator. By using the related parameters of the regulator depicted in 4.1.2.Young's modulus is also an important property of the friction material, and it is important to research its effects on the regulator characteristics. By using the related parameters of the regulator depicted in versus the Young's modulus are shown in 9 and 2 × 109 N/m2.As a result, plots of the output power, loss power and conversion efficiency 4.1.3.versus the thickness of the friction layer (varying between 0.2 mm and 1 mm) are shown in By using the related parameters of the regulator depicted in 4.1.4.By using the related parameters of the regulator depicted in 4.1.5.By using the related parameters of the regulator depicted in It can be seen that the output power and conversion efficiency show similar upward trends with an increase in the load torque. However, the loss power decreases gradually. Therefore, an increase in the load torque will not increase the loss power, which is produced by the friction between the stator and the rotor.4.2.Through the analysis of the dynamic model of the regulator by means of MATLAB, the simulation results allow one to determine the key parameters of the regulator. Using the parameters shown in i.e., the operating frequency of the regulator, is approximately 67 kHz. This value is slightly higher than the computational results. After that, an experimental test bench is established to measure the load torque/rotational speed relation of the regulator, as shown in It can be seen that the simulation accuracy is approximately 10% lower than the measured experimental rotational speed of the regulator. The simulated result of the stall torque is approximately 3% lower than the measured experimental stall torque. Several reasons can be given for this error between experimental and simulated values. The proposed dynamic model is an approximation of the actual regulator and a parametric model in which design and optimisation processes are possible. To achieve a balance between computational efficiency and accuracy, some of the necessary assumptions may cause modelling error. For example, a possible reason for the modelling error could arise from the fact that the rotor model does not include the rotor flexion because it was assumed to behave as a rigid body. Moreover, the in-plane bending vibration waves are assumed to be generated by a distributed force acting on the stator. This approximation also causes some degree of modelling error. However, the results from the simulations and experiments generally exhibit the same trend, and thus, the validity of the dynamic model is proven. To summarise, the mathematical model presented and analysed in this paper can be used as a tool for optimising the design of a piezoelectric dynamic balance regulator in steady state operation.5.etc. on the performances of regulator, and can be used to optimize design of the regulator.Based on the above model, MATLAB software is employed to numerically simulate characteristics of the regulator. Through the analysis of the dynamic model of the regulator by means of MATLAB, the simulation results allow one to determine the key parameters of the regulator. Using these parameters, a self-developed regulator prototype is fabricated, and its performance is tested experimentally. The experimental results are in good agreement with the simulation results, which demonstrates the effectiveness of the proposed method. Thus it can be seen that the numerical modelling approach to this complex problem has provided valuable insight into the mechanics and dynamics of the regulator. The model presented here lays the foundation for a general framework capable of the existing ultrasonic piezoelectric dynamic balance regulator and serving as a useful design tool for optimizing the key parameters of future regulators. The research on the model of the new piezoelectric dynamic balance regulator is still in its initial stages. For future applications of the regulator, systematic research and studies will be necessary. For example, the effects of stator teeth and the starting and stopping of the motor are not considered. These effects will be further researched in the future.In this paper, an ultrasonic piezoelectric dynamic balance regulator using the basic principles of a standing wave-type ultrasonic motor is proposed. Its overall structure and the actuation principle are introduced. The FEM and analytical analysis based modelling studies of the regulator are investigated in detail. The proposed model is simple and suitable for the study on friction behavior at the contact interface of regulator, and can simulate and analyze the effects of thickness and Young's modulus of friction layer, dynamic friction coefficient of contact interface, pre-load and load torque,


The most important point of the classification is the identification of β-catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage.In Europe and North America, hepatocellular adenomas (HCA) occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis). When nodules are multiple, they are usually of the same subtype. HNF1 The nodule is discovered in a context different to what we are used to see, such as in men, in women not exposed to oral contraceptives (OC), in older persons, or in children.per se may be difficult to identify due to the partial necrosis or to the major remodeling of the tumor leading to the presence of criteria seen mostly in focal nodular hyperplasia (FNH) and/or to difficulties in differentiation from hepatocellular carcinoma (HCC). The tumor The presence of an underlying liver disease such as nonalcoholic steatohepatitis (NASH), vascular disorder, and fibrosis.HCA, HCC, and FNH or different HCA subtypes can be present in the same patient, some more prone to HCC transformation, with the difficult task, in some cases, to differentiate HCA from HCC.Finally, HCA can be discovered unexpectedly in patients treated for other liver tumors or developed in the context of diseases affecting the liver or other organs.The diagnosis of hepatocellular adenomas (HCA) may occasionally be difficult for the following reasons.α-inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin activated HCA (b-HCA and b-IHCA) and unclassified HCA (UHCA).In this paper, we review the clinical/epidemiological context of HCA, based on our experience ; all these cases being classified according to the pathomolecular classification into four groups, as previously published are HNF11) The great majority of HCA occurs in middle age women genitally active, taking OC (at least in many Northern European countries and in North America) [ The greaIf the role of OC in the development of HCA is certain, the individual susceptibility to the risk is of paramount importance. No particular HCA subtypes have been observed in women; however, HCA in very young women (in their twenties) taking or not OC without specific etiology are rare and found, in our experience, mainly in the b-HCA and UHCA subgroups.2) HCA in men are rare  HCA in m. To the (3) HCA occurring in infants, adolescents, or young adults are mainly related to specific etiology such as vascular disorders, familial adenomatous polyposis (FAP), or MODY 3. (4) HCA in patients over 65 are rare. We have observed 4 H-HCA cases, all in women. (5) In addition to age, gender, OC, and background liver diseases (see below), the biological and radiological parameters are also good indicators of HCA subgroups. Radiologists are now able to identify with confidence typical H-HCA and IHCA. Furthermore, a raised CRP level in the blood is a strong argument to identify IHCA. It is well admitted that HCA may transform into HCC –25. HoweHCC that developed on HCA are typically well differentiated without vascular extension or satellite nodules. AFP measurement is not reliable as it is usually normal. The prognosis is—compared to HCC in cirrhotic patients—relatively good if we consider that tumors are usually large tumors (>5 cm).Prevalence of malignancy within HCA is 10 times more frequent in men than in women and management of HCA should primarily be based on gender. In addition to men, reported cases of HCC on HCA concern rare etiologies such as glycogenosis, male hormone administration, and vascular diseases. Metabolic syndrome also appears as an emerging condition associated with malignant transformation of HCA particularly in men and is the likely most frequent predisposing condition for HCC in this setting. For the pathologists, there are different degrees of difficulties to make the diagnosis of HCA transformation into HCC . (1) The tumor is definitively an HCC: malignant transformation of an HCA is likely when the HCC occurs in a specific context such as glycogenosis, male hormone administration, or when the diagnosis of HCA has been established several years before. The link exists but cannot be demonstrated when the cause of the putative HCA is not well documented , or when there are areas in the tumor, particularly at the border, looking benign but that could correspond to a very well-differentiated HCC. (2) The tumor is benign but there are foci with cytological/architectural criteria in favor of premalignant changes .(3) The tumor is possibly malignant, at least in part . In many occasions, the diagnosis of true malignancy remains impossible to assert and the term “borderline tumor HCA/HCC” can be used. In our own series, we observed 17 cases of HCC possibly linked to HCA with 2 deaths .Many different types of hepatocellular nodules ranging from nodular regenerative hyperplasia (NRH), focal nodular hyperplasia (FNH), and macroregenerative nodule (MRN)/FNH-like, to HCA and HCC have been described in different types of vascular disorders –42 such  In a large series of 43 patients published in 1997, 51.8% of patients with type 1 and 25% of patients with type 3 glycogen storage disease had HCA at the time of the study. The male to female ratio was 2 to 1 in type 1, and no female had adenomas in type 3 . Immunohα [ HCA in patients with FAP have been reported previously , 47–50 wα  as well α , 50. Malα . In our  The discovery of H-HCA in MODY3 is a great success of molecular biology with important clinical consequences –55. The  Cases of HCA have been reported in tyrosinemia . The diaHCA and HCC have been reported in patients taking male hormones for medical purposes, that is, Danazol –59, or tβ-catenin activated IHCA subgroups. Overweight/obesity may soon represent a major risk of malignant transformation of HCA, possibly because of the activation of the IL-6 pathway. In HCA, the nontumoral liver is usually normal or subnormal. Steatosis (mild to severe) is quite often observed in overweight/obese patients with or without metabolic syndrome; NASH is rare [The number of HCA noticeably increased faster in the 2001–2011 period compared to the 1990–2000 period. This phenomenon concurred with an increasing number of patients overweight or obese –69. More is rare . Most of Fanconi anemia. The Fanconi anemia is an autosomal recessive disease, causing secondary aplastic anemia and congenital abnormalities, associated with an increased risk of tumors [(1)f tumors , 71, 72. beta thalassemia. Hepatocellular adenoma has been reported [(2)reported . Anemia of chronic disease. In 2002, severe anemia of chronic disease was described in an unusual group of patients with glycogen storage disease type 1a. The anemia was directly related to the presence of large hepatic adenomas that inappropriately produced hepcidin [(3)hepcidin , 74. A shepcidin . In our hepcidin . In patihepcidin .  Polycystic ovary syndrome. A case of a young woman with HCA in a context of polycystic ovary syndrome, associated with high levels of androgens and following a high dose hormonal therapy, has been described [(1)escribed . We obse Cushing's syndrome. To our knowledge no case of HCA has been reported yet in Cushing syndrome patients. In our file, one b-HCA occurring in a patient with a Cushing syndrome became malignant years later; however, this old case was poorly documented.(2)In severe fibrosis/cirrhosis, the diagnosis of HCA was not reported until recently in alcoholic patients . Here thWe have observed HCA associated with other tumors occurring elsewhere in the liver. In all these cases, HCA were in the H-HCA subgroup, associated with an HCC, an angiomyolipoma, and a mucinous cystadenoma, and one was associated with cysts in the context of a kidney polycystic disease . These aAssociation of HCA and FNH. The association is probably not fortuitous. FNH are particularly frequent in adenomatosis, and it is not rare that small H-HCA could be fortutiously discovered on the resected specimen  In 1989, Wanless et al. reported 13 cases with multiple FNH associated with other lesions such as hemangioma of liver meningioma, astrocytoma, telangiectasia of the brain, berry aneurysm, dysplastic systemic arteries, and portal vein atresia . In the a priori, a metastasis. We have encountered 3 patients already treated by chemotherapy where HCA were discovered by chance during the followup.(2) HCA are so rare that patients with cancer  and a nodule in the liver are thought to have, Iron  or otherAbnormalities such as mainly dystrophic nuclei or 2-3 cells thick hepatocytic plates are often seen when HCA exhibits large hemorrhagic/necrotic areas . These mHCA can also be remodeled following necrosis/hemorrhage. Fibrotic bands and even scars can form so that HCA look like FNH; these changes are more frequently seen in IHCA subtypes . The argα-inactivated adenomatosis, there are myriads of small HCA that tend to aggregates to form larger nodules [α adenomatosis where such large nodules were interpreted as increasing in size, requiring reintervention (HCA are solitary or multiple (from few to many). Many HCA defined the so-called entity adenomatosis (arbitrarily more than 10 nodules). For surgeons, adenomatosis is defined also by the number of nodules whose size raises therapeutic decision. Therefore, we have to distinguish cases with a single large nodule accompanied by myriads of small millimetric nodules from cases with multiple large nodules. Adenomatosis is more frequently observed in H-HCA and to a lesser extent in IHCA [ nodules . We havervention . It is nIf it is tempting to publish rare cases, such as HCA with unusual cytological abnormalities, HCA in rare pathological context , HCA associated with rare hepatic or extrahepatic tumors, HCA have to be classified in subgroups with the help of IHC, to understand the pathophysiology of the disease and, in the long term, to better diagnose liver tumors and adapt the management of the patients. Not all HCA can be correctly classified with histological tools only. To prevent this limitation, it is recommended to freeze tissue, in order to perform molecular studies, that are particularly important to understand unusual and unclassified HCA cases. It is hoped that the pathomolecular classification of hepatocellular adenomas developed on normal as well as on fibrotic liver will help us to make progress in this field.


Video Sensor Networks (VSNs) are recent communication infrastructures used to capture and transmit dense visual information from an application context. In such large scale environments which include video coding, transmission and display/storage, there are several open problems to overcome in practical implementations. This paper addresses the most relevant challenges posed by VSNs, namely stringent bandwidth usage and processing time/power constraints. In particular, the paper proposes a novel VSN architecture where large sets of visual sensors with embedded processors are used for compression and transmission of coded streams to gateways, which in turn transrate the incoming streams and adapt them to the variable complexity requirements of both the sensor encoders and end-user decoder terminals. Such gateways provide real-time transcoding functionalities for bandwidth adaptation and coding/decoding complexity distribution by transferring the most complex video encoding/decoding tasks to the transcoding gateway at the expense of a limited increase in bit rate. Then, a method to reduce the decoding complexity, suitable for system-on-chip implementation, is proposed to operate at the transcoding gateway whenever decoders with constrained resources are targeted. The results show that the proposed method achieves good performance and its inclusion into the VSN infrastructure provides an additional level of complexity control functionality. In this context, wireless sensor networks (WSNs) are commonly comprised of a set of nodes, each one typically including a sensor, microcontroller, power supply and a wireless communication device . There aIn the particular case of visual sensor networks (VSNs), the sensor nodes consist of a camera and a video encoder to compress the video data before transmission. VSNs are certainly among the most challenging sensor networking infrastructures to deploy, because the stringent requirements of low transmission bandwidth and low power consumption impose strong constraints on the visual sensors, particularly on video encoders .There are many sensor networking applications that can significantly benefit from the presence of video information. These applications include either video-only sensor networks or sensor networking applications in which video-based sensors augment their traditional scalar sensor counterparts . Exampleetc. [In the past there was a great research focus on the sensors themselves, their characteristics and the optimization of different parameters, such as size, power consumption, processing power, memory, transmission rate, etc. . Howeveri.e., a review of efficient methods to control the complexity of video encoders in the light of their use in VSNs and a novel framework to gather video streams from multiple visual sensors with the capability of reducing their decoding complexity by using a novel type of video transcoding for this specific purpose.This paper addresses the problems referred to above, The rest of the paper is organized as follows: Section 2 provides a short description of the main concepts of VSN video sensor nodes. Section 3 addresses the problem of video coding complexity for VSNs. Section 4 presents the proposed VSN architecture with distributed video coding/decoding complexity. Section 5 discusses the complexity associated with video decoding and Section 6 presents an algorithm for reduction of decoding complexity. Finally Section 7 presents the simulation results and Section 8 concludes the paper.2.In the past, several different research topics have been addressed in the field of both generic WSNs ,5,7 and Typically, how to simultaneously provide video quality and energy efficiency from low resource nodes is the main problem, because VSNs generate a large amount of data, hence processing and transmission of video data causes them to consume a great quantity of energy. For instance, a single low-resolution image of QVGA (320 × 240) at 12 bits/pixel will generate 115,200 bytes of data which corresponds to a transmission rate of 23.04 Mbps, in case of video at 25 frames/sec. How to extend the lifetime of nodes and also to balance the energy consumption of the whole network, is a critical factor in VSNs. This imposes much tough stringent requirements on the network nodes and interconnection infrastructure than only the amount of available RAM memory on a typical wireless sensor node, as usually referred to as a relevant limiting factor in WSNs ,11. TherIn the case of wireless VSNs, a specific dedicated communication infrastructure is not absolutely necessary, since these are self-organizing and highly dynamic structures, with each communication node serving as both server and router for data transmission –16. A ty2.1.Single-tier flat architecture having homogeneous sensors.Single-tier clustered architecture having heterogeneous sensors.Multi-tier heterogeneous architecture with heterogeneous sensors support.The current VSN architectures are classified in three broad categories, according to the type of organization and clustering used for the sensors, which in turn depend on the envisaged application and also on the physical characteristics of the whole environment. A generic VSN is depicted in The multi-tiered architecture shown in i.e., not only visual information, but also other types of physical variables). A central processing unit can be used in each cluster in order to deal with intensive processing tasks which would be too heavy for the sensor nodes with small processing/storage capacity. Then sensory information collected at the sensor nodes is also transmitted hop-by-hop to the storage/sink node via the gateway. This architecture can be used in a wide range of applications because the heterogeneous nature of the sensors is not restricted to any predefined type.The single-tier clustered shown in The single-tier flat architecture shown in 2.2.A challenging application field of VSNs is remote surveillance, where the video content must be streamed to some central monitoring point. As mentioned before, this requires relatively complex processing  and high transmission bandwidth. In general, these networks are adapted to the environment dynamics and are able to respond timely to a user’s request. It is worthwhile to point out that such VSNs are not necessarily limited by the absence of infrastructure nor do they require central servers with large resources .VSNs can also be used in environmental monitoring applications where sensors are deployed in remote and inaccessible areas over long periods of time, e.g., sandbank evolution or control of animal population. Often cameras are combined with other type of sensors in order to be triggered only when an event is detected by other sensors in the network –20. SuchElderly personal and health care monitoring is another field of application targeted by VSNs. In this case, the inclusion of additional telemedicine devices extend the use of VSNs to remotely monitoring patient’s health parameters such as blood pressure, body temperature, heart rate, breathing activity, and movements within a certain living area .The VSN technology also enables applications where remote users can “visit” some location that is monitored by a set of video cameras–such schemes are usually known as telepresence systems . ExampleTraffic congestion management is another potential growing application scenario for these networks. In general this type of application leads to large arrays of information sources as a result of the widespread use of information and communications technologies in road sensors, electronic toll collection devices, automatic video processing, global positioning systems, mobile sensor networks and smart phones. In this type of applications, VSNs play an important role to enable integration of diverse information about real time traffic and status for intelligent traffic routing. An example of a traffic monitoring system, using different types of sensory information with video playing a major role, is described in .2.3.The technology used in most video sensors and hardware platforms derives from other application fields, though particular attention is given to power consumption in the case of VSNs . NowadayThe image quality provided by CMOS technology is now reaching the same level as CCD quality in the low and midrange, while CCD is still the technology of choice for high-end image sensors. The CMOS technology allows integrating a lens, an image sensor and image processing algorithms, including image stabilization and image compression, on the same chip. With respect to CCD, cameras are smaller, lighter, and consume less power. Hence, they constitute a suitable technology to realize imaging sensors to be interfaced with wireless nodes. 3.As visual information deals with a considerable amount of data, video sensors must use compression to reduce the amount of data in order to effectively save storage memory and also to fit the data on the available network bandwidth. The H.264/Advanced Video Coding (AVC) is an industry standard for video compression , September 2004; v4, July 2005 #599). The H.264/AVC standard, also known as MPEG-4 Part 10, is a successor to earlier standards such as MPEG-2 and MPEG-4 Visual. The H.264/AVC achieved the target to double the coding efficiency  in comparison to any other existing video coding standards for a broad variety of applications. This coding efficiency improvement comes at a cost of significant increased codec complexity, which increases the hardware requirements and power consumption for encoding and decoding.i.e., macroblocks (MBs). Slices are typically encoded as either Intra (I), Predictive (P), or Bi-Predictive (B) where I slices are encoded using predictive pixels from the same frame and are independent of all others, P slices use inter-frame prediction methods as well as intra-prediction methods and B slices use an expanded set of forward and/or backward inter-prediction methods compared to P-frames. For P and B slices, motion estimation (ME) is carried out for each MB to find the best match from a reference frame. In H.264, each MB can be further partitioned into sub-blocks and multiple reference frames can also be used. An integer transform (IT), with similar characteristics to those of the discrete cosine transform (DCT) used in previous standards, is applied to the block residue, concentrating most of the block energy into the low frequency region. Quantization and entropy coding of the remaining coefficients are then applied to further reduce irrelevancy and redundancy of the video signal.As in previous video coding standards, the H.264/AVC video codec defines the video signal structure as a series of groups of pictures (GOPs) comprising frames of luminance (Y) and two chrominance (Cb and Cr) pixels. Each individual picture is organized into slices which in turn are divided into non-overlapping blocks, In H.264/AVC most of the coding efficiency comes from exploiting temporal redundancies within the video sequence by performing block based motion compensated prediction. However, motion estimation is only performed at the encoder, and the motion vectors have to be explicitly coded into the bit stream. Motion estimation is among the most complex operations in H.264/AVC video coding because of the huge number of operations involved in finding the best match for each macroblock (MB) or block. Also on the decoder side, previous studies on H.264/AVC decoder complexity have shown that motion compensation (MC) is the most computationally complex functional block at the decoder, followed by the deblocking filter process ,26, as w3.1.Video coding for the VSN must be done in a different manner from the coding for video telephony or other multimedia applications. This difference is mainly due to two features associated to the sensor networks: (1) limited resources and (2) data quality. The first feature is a critical aspect in VSN since video cameras collect a huge amount of data that must be transmitted over a wireless link, as pointed out before. Therefore video compression must be used to reduce the amount of data to be transmitted, but this can only be obtained at very high computational cost. The second feature leads to the fact that while video compression algorithms often have very powerful data reduction capabilities, they introduce significant distortion . When thA different paradigm that fits the requirements of VSNs is Distributed Video Coding (DVC) ,30. The 4.i.e., the video sensors and the end-user terminals. The transcoding gateway is responsible for matching the complexity requirements of both ends.The proposed VSN architecture with distributed complexity control capability is depicted in 4.1.The general architecture of the transcoding gateway is shown in i.e., transrating the input stream, and also takes into account the type of end-user terminal. In the case of mobile or portable devices, the encoder activates its complexity-aware coding mode in order to produce streams with low decoding complexity. As a consequence the bit rate might be slightly increased, while the decoding complexity can be significantly reduced. In the next sections a decoding complexity-aware method for standard video encoders is proposed and described in detail, along with results and discussion.The video encoder of the transcoding gateway plays the important role of matching the output rate to the bandwidth constraints of the outgoing transmission channel, 5.etc. are increasingly used to access, decode and render multimedia content in which compressed video plays a major role. The limitation imposed by battery life and computational constraints of processing equipment have been a strong motivation for research on complexity issues of video coding and decoding systems in the last few years [etc., in video decoders this is highly related to the computational complexity of the decoding process. It is particularly relevant in the case of H.264/AVC video coding standard where complexity, at both the encoding and decoding sides, is a major concern in any practical real time implementation. Besides all implementation optimizations that can be considered for the purpose of minimizing decoding complexity, there is still room for further reduction by producing compressed video streams such that their inherent decoding complexity is made lower [Current portable devices such as mobile phones, personal digital assistants, palmtops, ew years –40. Exteew years  and powede lower ,43. ThisThe decoding complexity of H.264/AVC streams is mainly because of motion compensation due to sub-pixel accuracy computations which demand for a great deal of processing. This is because computation of predictions from sub-pixel motion vectors is done by interpolation filters which need a different amount of filtering operations according to the location of the sub-pixel to be determined. In the next section we propose a measure of decoding computational complexity based on the amount of filtering operations needed to compute sub-pixels in order to account not only for rate and distortion but also for decoding complexity in the process of selecting the best motion vector for each block. Then the rate-distortion complexity performance is evaluated and compared with the normal rate-distortion optimized coding.6.Video encoding complexity has been a research issue in the last decades, either when new standards or coding algorithms emerge with more efficient coding tools than their main predecessors. Since on the decoder side, the problem of complexity is strongly dependent on the encoding side, different approaches can be used to limit the computational complexity required to decode video streams. For instance, in the MPEG-4 visual standard a video buffer verifier mechanism was defined to bound the decoding complexity of coded streams . Another6.1.Motion estimation is among the most complex operations in H.264/AVC video coding because of the number of operations involved in finding the best match for each MB or block. Also on the decoder side, previous studies on H.264 decoder complexity have shown that motion compensation (MC) is the most computationally complex functional block at the decoder, followed by the deblocking filter process.High complexity in motion compensation is mainly due to the interpolation needed to decode motion vectors with half or quarter pixel accuracy. For the baseline H.264 decoder, it was shown that interpolation takes around 39% of the execution time on average, and it can go up to 44% for some sequences. 6.2.In H.264/AVC video coding, the bit allocation and rate control mechanisms dynamically adjust the encoding parameters to achieve a target bit budget at the highest possible video quality. This is done through rate-distortion Lagrangian optimization in two coding stages: motion estimation and mode decision. In the first one, motion estimation, for each block B with a block mode M, the motion vector associated with the block is selected through a rate-distortion joint cost function:DFD is the prediction error, computed as either the sum of absolute differences (SAD) or the sum of squared difference (SSD), RMotion is the estimated bit rate to encode the corresponding motion vector, λMotion is the Lagrange multiplier to control the weight of the bit rate cost relative to the prediction error. Motion and DDFD. Since in general the search space for motion vectors is very large and SAD has lighter computation cost than SSD, the former is used more often.i.e., a rate-distortion-complexity joint cost function as given by Motion is the complexity cost associated with the selected motion vector and λCMotion is the Lagrange multiplier for the complexity term. In this work, in order to favour motion vectors with less interpolation complexity and penalize the ones with higher complexity, the conventional cost function presented in lowed in .ModeC is the complexity cost associated with the selected block mode and CModeλ is the Lagrange multiplier for the complexity term. CMotionλ = CModeλ = 0 the solution for i.e., the complexity cost is not considered and motion vectors are chosen based only on the rate-distortion cost without taking into account the inherent decoding complexity of half and quarter-pixel accuracy motion. At the other extreme, CMotionλ = CModeλ = 1 results in minimum decoding complexity because complexity cost is dominant. However in this case the rate-distortion performance drops, thus the best solution is to tradeoff between rate, distortion and complexity using 0 < CMotionλ = CModeλ < 1, i.e., varying the Lagrange multiplier between 0 and 1 for the complexity term, in both The MB mode is directly related to the computational complexity because it defines which motion vector should be associated with each of its sub-blocks. For each motion vector, a prediction block must be computed by the decoder in order to reconstruct a predicted MB from all sub-blocks. After all inter mode candidates have an associated motion vector, the coding results of the modes are compared and the one that minimizes the following Lagrangian cost function is chosen according to 6.2.The efficiency of the proposed constrained coding method was experimentally evaluated in order to assess how decoding complexity can be reduced and how much quality drop is observed. Two sequences (Container and Foreman) with different types of motion were used in order to assess the influence of the video signal characteristics on the performance of the proposed method. The baseline mode of H.264/AVC was used as this is more appropriate to mobile devices. The experimental setup was defined according to the recommended simulation conditions for coding efficiency experiments ,47. As sCλ because the choice for integer motion vectors increase while sub-pixel interpolation decreases because the complexity weight is higher in the Lagrangian cost function. Cλ as used in Cλ. As it can be seen in this table, the small decrease in rate-distortion  performance shown in The difference is greater for higher values of 8.In this paper we have proposed a novel architecture for VSNs where the computational complexity is taken into consideration. A new networking element, the transcoding gateway, was presented as a central processing, which can concentrate part of the encoding complexity from the video sensors and reduce the decoding complexity required from the end user terminal. Such a framework has high flexibility and scalability, making it suitable for many different applications. Furthermore we have also proposed an algorithm to produce low decoding complexity streams at the transcoding gateway. The results show that a significant complexity reduction can be achieved at the expense of a small reduction in coding efficiency. This algorithm is currently under implementation as a standalone processing module using FPGAs.


WAF1/CIP1 in various tissues.Hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, enhances hepatocyte function without stimulating proliferation, depending on the physiological conditions. p53, a transcription factor, suppresses the cell proliferation by expressing p21To investigate the mechanism through which the hepatocytes maintain mitotically quiescent even in the presence of HGF.We studied the relationship between p53 and p21 expression and the effect of p53-p21 axis on hepatocyte proliferation in primary cultured rat hepatocytes stimulated by HGF. Hepatic p21 levels are determined serially after partial hepatectomy or sham operation in rats.DNA synthesis was markedly increased by HGF addition in rat hepatocytes cultured at low density but not at high density. Cellular p53 levels increased in the hepatocytes cultured at both the densities. p21 levels were increased and correlated with cellular p53 levels in hepatocytes cultured at high density but not at low density. When the activity of p53 was suppressed by a chemical inhibitor for p53, cellular p21 levels were reduced, and DNA synthesis was increased. Similarly, p21 antisense oligonucleotide increased the DNA synthesis. In rats after partial hepatectomy, transient elevation of hepatic p21 levels was observed. In contrast, in sham-operated rats, hepatic p21 levels were increased on sustained time scales.p53-related induction of p21 may suppress hepatocyte proliferation in the presence of HGF in the setting that mitogenic activity of HGF is not elicitable. Proliferation of hepatocytes occurs following the loss of parenchymal cells, while hepatocytes are usually mitotically quiescent. Hepatocyte growth factor (HGF), originally identified as a potent mitogen for hepatocytes in culture, has a pluripotent effect on various types of cells Though recent several reports including ours indicate that p53 can stimulate cell proliferation by the specific induction of promoters for growth-associated factors such as TGF-α, p53 is generally recognized as a ‘tumor suppressor gene’, because, in some pathophysiological conditions, it up-regulates p21, which arrests cell cycle at G1 phase, and inhibits cell proliferation both in vitro and in vivo In this paper, we showed that p21 was up-regulated by HGF stimulation through the induction of p53, and suppressed hepatocyte proliferation in the setting that mitogenic activity was not elicitable.Hepatocyte extracts were prepared according to the protocol from the manufacturer of the p53 enzyme-linked immunosorbent assay (ELISA) kit  Liver tissues and cultured hepatocytes were homogenized in the low salt resuspension buffer  aminomethane, 5 mmol/L ethylenediaminetetraacetic acid, 0.2 mmol/L phenylmethylsulfonyl fluoride 1 µg/mL pepstatin and 0.5 µg/mL leupeptin). The suspensions were incubated with p21 antigen extraction agent ), and centrifuged. The resultant supernatants were applied to ELISA described below.The sandwich ELISA for p21 was developed using polyclonal anti p21 IgG  and monoclonal p21 antibody  as capture and detector antibodies, respectively. Horseradish peroxidase conjugated goat anti-mouse IgG  was used to detect the antibody-p21 complex.The standard curve for p21  of this assay made with the buffer showed the lower limit at 1.25 ng/mL. When the sample of rat liver prepared for p21 assay was diluted with the buffer, the dilution curve was similar to the standard curve. When p21 protein was diluted with sample of rat liver or hepatocytes prepared for p21 assay, the dilution curve was similar to the standard curve.Incorporated BrdU was determined by ELISA, using BrdU labeling and the detection kit III . The total cellular protein was measured by Bradford's method 5 cells/cm2 (high density culture) or 2.5×104 cells/cm2 (low density culture) in the medium and incubated for 27 hours as we previously reported Hepatocytes were isolated from rat livers according to Seglen's method To study the effect of inhibition of p53 function on p21 levels and DNA synthesis in hepatocytes, the hepatocytes were cultured in WE containing 10% FCS, with or without 10 ng/mL HGF, 1 mmol/L BrdU and various concentrations of pifithrin-α  dissolved in dimethyl sulfoxide (DMSO) or the same concentrations of DMSO 5′-GACATCACCAGGATCGGACAT-3′), complementary to position 85–105 of rat p21 mRNA, or nonsense oligonucleotide (5′-GCAACGCTACTACGCAAGTAG-3′), containing the same numbers of G, C, A, and T as the p21 antisense oligonucleotide To examine the effect of inhibition of p21 production on hepatocyte DNA synthesis, the hepatocytes were cultured in WE containing 10% FCS, 10 ng/mL HGF, 1 mmol/L BrdU and various concentrations of either p21 antisense oligonucleotide  were subjected to either of two-thirds partial hepatectomy (PH) or sham operation under diethyl ether anesthesia. In sham-operated rats, the abdomen was cut open under similar anesthesia, and the liver was briefly exposed outside the peritoneal cavity. The rats were serially anesthetized with diethyl ether. The liver was perfused through the portal vein with saline. After a near total exsanguination, the liver was excised and used for the p21 assays.All animal study protocols conformed to and approved by the guideline of the Faculty of Medicine, University of Tokyo for humane care.t-test and the Mann-Whitney U test were less than 0.05. The dose related effects were tested by one-way analysis of variance followed by Spearman's correlation test.The differences between two unpaired samples were defined as significant when the p-values by both the Student's We determined the effect of cell density on DNA synthesis of cultured hepatocytes simulated by HGF. The addition of 10 ng/mL HGF to the medium caused only minor increase on DNA synthesis in hepatocytes cultured at high density. In hepatocytes cultured at low density, DNA synthesis increased after 12 hours of incubation, peaked at 24–30 hours and decreased thereafter by HGF addition . DNA synTo investigate the effect of HGF on p53 and p21 expressions and their relationship in proliferating and non-proliferating rat hepatocytes, we determined p53 and p21 protein levels in cultured hepatocytes at low and high density in the presence of various concentration of HGF.As shown in The levels of p53 in high density cultured hepatocytes treated with 10 ng/mL HGF increased after 6 hours and reached a maximum at 24 hours (data not shown), while, in low density cultured hepatocytes treated with 10 ng/mL HGF, p53 levels significantly increased from 6 hours and peaked at 18 to 24 hours of incubation, similar to our previous report The levels of p21 protein in high density cultured hepatocytes treated with 10 ng/mL HGF increased in a time dependent manner . When hep21 levels were increased in a dose related manner by HGF and correlated with p53 levels at high density cultured hepatocytes, while, at low density cultured hepatocytes, p53, but not p21, levels were increased by HGF and there was no correlation between p53 and p21 levels.To elucidate the relationship between p53 expression and p21 expression as well as DNA synthesis in hepatocytes at non-proliferating condition even in the presence of HGF, we determined the effect of pifithrin-α, a chemical inhibitor of p53, on p21 levels and BrdU incorporation of hepatocytes cultured at high density in the presence of HGF.The levels of p21 treated with 10 ng/mL HGF for 18 hours in hepatocytes at high density were reduced by the addition of pifithrin-α, a chemical inhibitor of p53, when compared with the addition of vehicles (p<0.01) .In contrast, the levels of p21 in hepatocytes at high density treated without HGF for 18 hours, the values of p21 protein were 211.5±24.9 µg/g protein (mean±standard error), and did not show any significant changes by the addition of pifithrin-α when compared with the addition of vehicles (202.2±57.4 µg/g protein). In addition, the levels of p21 in hepatocytes cultured at low density treated with 10 ng/mL HGF for 18 hours were not affected by pifithrin-α treatment (121.7±18.1 µg/g protein vs137.6±21.8 µg/g protein).The levels of BrdU incorporation treated with 10 ng/mL of HGF for 24 hours were increased significantly by the addition of 2 µM of pifithrin-α, when compared with the addition of vehicles (p<0.01) . The totp21 levels were reduced and DNA synthesis was significantly increased by pifithrin-α a chemical inhibitor of p53, in the presence of HGF in high density cultured hepatocytes.We investigated the effect of suppression of p21 expression on DNA synthesis in non-proliferationg hepatocytes in the presence of HGF. BrdU incorporation in hepatocytes cultured at high density in the presence of 10 ng/mL of HGF was significantly increased after a 24-hour exposure to p21 antisense oligonucleotide, when compared with that of hepatocytes treated with the nonsense oligonucleotide (p<0.01) . The totTo study p21 expression profile in regenerating and quiescent rat liver, we determined hepatic p21 levels in rats after PH and sham operation. Hepatic p21 levels were increased to the maximal levels at 4 hours, and decreased to the basal levels at 8 hours after PH with minor increase at 48 hours. In contrast, hepatic p21 levels of sham-operated rats were increased up to 2.5-fold higher than preoperative levels at 12 to 48 hours and decreased to the preoperative level at 72 hours. Hepatic p21 levels were significantly higher in sham-operated rats than in rats after PH except within 4 hours after surgery . In shamWe confirmed that DNA synthesis was not induced significantly in hepatocytes cultured at high density even in the presence of HGF, as we previously reported in vitro and in vivo using newly developed ELISA system. Although p21 expression has been extensively studied in proliferating and non-proliferating hepatocytes and in the liver with or without regenerative stimuli in vitro and in vivo.We determined p21 protein levels in vitro and in vivoWe suppressed p53 activity and p21 expression using pifithrin-α and a p21 antisense oligonucleotide, respectively. Pifithrin-α disturbs the nuclear transport of p53 leading to the inhibition of the function of p53 Previously, we reported that the addition of HGF to the medium increased p53 contents in hepatocytes cultured at low density followed by the increase of DNA synthesis by hepatocytes p21 is known to be induced by p53-dependent and -independent mechanisms according to the cell types and situations Previous several reports have shown that growth factors can induce p21 production and suppress cell proliferation. Transient induction of p21 mRNA following stimulation of growth factors such as EGF, platelet-derived growth factor and fibroblast growth factor is reported in several cell lines, leading to cell cycle arrest Previous experiments in rats showed that hepatic levels of p21 protein after PH determined by Western blot analysis were increased at two time points, first immediately after resection and second after the peak of DNA synthesis. In sham operated rats, the p21 levels were almost undetectable throughout the 7-day time course


A low-complexity saliency detection algorithm for perceptual video coding is proposed; low-level encoding information is adopted as the characteristics of visual perception analysis. Firstly, this algorithm employs motion vector (MV) to extract temporal saliency region through fast MV noise filtering and translational MV checking procedure. Secondly, spatial saliency region is detected based on optimal prediction mode distributions in I-frame and P-frame. Then, it combines the spatiotemporal saliency detection results to define the video region of interest (VROI). The simulation results validate that the proposed algorithm can avoid a large amount of computation work in the visual perception characteristics analysis processing compared with other existing algorithms; it also has better performance in saliency detection for videos and can realize fast saliency detection. It can be used as a part of the video standard codec at medium-to-low bit-rates or combined with other algorithms in fast video coding. With the rapid developments of multimedia information processing and communication technology, video encoding has become the basic core technology of digital television, video conferencing, mobile media, 3D video coding, and so forth. During the past decades, in order to obtain video codec with low complexity, high quality, and high compression ratio, various technologies have been proposed for fast video coding .Studies have shown that human visual system (HVS) is sensitive to the video scene perception and assigns different visual importance to different regions , 3. ReseUp to now, saliency detection algorithms are widely used in extracting ROI in videos for various multimedia processing applications –8. MovinThose saliency detection algorithms mentioned previously are facing a common problem: they are not only time-consuming but computation-consuming as well. Those algorithms do not pay more consideration to the effect of the real-time coding performance because of the additional computation for visual perception analysis. Complex saliency detection algorithm will increase the computational burden of video encoder, which is not conducive to the video coding standards in real-time multimedia communication application.In this paper, a fast saliency detection algorithm based on low-level encoding information and HVS is proposed. In order to simplify the visual perception analysis progress, this algorithm correlates the encoding information in video bit-stream with the visual perception characteristics. The spatial and temporal saliency detection is carried out by means of MV. The prediction modes and other auxiliary coding information can save an amount of computing time in feature extraction for saliency detection. As almost no additional computation is increased to the video codec, the saliency detection computation complexity is lower compared with other existing algorithms. The saliency detection results are satisfied with the compared algorithms. So the proposed algorithm can reach the balance between the saliency detection accuracy and computational complexity.This paper is organized as follows. Motion is a highly salient feature which grabs one's attention and keeps it locked on important features and objects. Interest in motion perception has a long history and it can be considered as a relatively well established discipline . Motion The response intensity of temporal motion visual information caused by HVS is larger compared with that of spatial motion visual information caused by HVS . In the As we know, moving objects always have larger MV in video frame. It can be found in In an ideal case, foreground moving object can generate nonzero MV. As there are no relative movements in the background region, it should produce zero MV in static background. However, in reality, nonzero MV noise would be generated randomly due to external change of illumination and internal change of video encoding parameters . As a result, corresponding MV detection mechanism should be proposed to get rid of the interference of MV noise.Besides the MV noise interfering in temporal saliency detection, the translation MV interfering from the background should be considered. As shown in In order to improve the temporal detection accuracy, the MV noise filtering and the attenuating translation MV interference error should be added. At the same time, the complexity of processing procedure should be controlled strictly. Otherwise it will influence the real-time performance of the saliency detection algorithm.1) Basic Principle of MV Noise Filtering. Compression coding uses the correlation between adjacent macro blocks to remove redundant information on spatial domain or temporal domain, in order to achieve a large amount of information with a small number of bits. In video coding framework based on blocks, the coded object is usually divided into several macro blocks or subblocks; then the macroblocks or subblocks that belong to an object should tend to have a similar motion vector or predictive coding mode and have similarity in structure  represents the round numbers calculation.In (ii) Crr  with Vertical Motion. If ③  Crr are as follows.jc macro blocks in the opposite direction of c.Firstly, take MB-1 as the starting point, then perform vertical motion of jc macro blocks both leftwards and rightwards to obtain two horizontal vertices: MB-3 signed c and MB-4 signed c.Secondly, centered at MB-2, make horizontal extension of ③; Crr is designated and surrounded by four macro blocks which are MB-3, MB-4, MB-5, and MB-6  Crr  with Oblique Motion. If ⑤  Crr, ⑥  Crr, ⑦  Crr, and ⑧  Crr in the same way according to the different motion directions of Crr is given in The position coordinates of MB-1 to MB-9 are given in ic and jc are defined as formulas (In formulas  and 2)..ic and Crr is not stationary, and the area and position of Crr are changed adaptively according to the size and direction of In the proposed algorithm, reference region 3) The MV Noise Filtering Computational Formula. Consider denotes the position coordinates of current encoding MB.In formula , V¯rr isT1 = 3.If Crr, and the current encoding block belongs to dynamic foreground region which should be marked as 2, T1 = 2.If Crr, and the current encoding block's temporal saliency characteristics are undetermined. So the translational MV checking should be carried out further in order to distinguish whether current encoding MB belongs to background region or foreground translation region.Else, it means the current encoding MB has similar motion characteristics as its nearby MBs in After MV noise filtering procedure, the translation MV interference attenuating step comes into consideration.1) Basic Principle of Translational MV Checking. In video coding based on the block matching, first step is to get the difference value between the best matching block and the original block, namely, the prediction error. If the prediction error value is smaller, after discrete cosine transform (DCT) transform the high frequency coefficients is less, then appearing probability of all zero quantized coefficients will be higher, and when number of coding bits is fewer, the higher the compression will be, which means the current block and the predicted block has more matching higher structural similarity, and the prediction coding effect is better., 0 ≤ m, n ≤ 3, its transformation coefficient is E computational formula is as follows:For a residual value of prediction error for 4 × 4 subblock u, v = 0, u, v ≠ 0, C(u), C(v) = 1. [·] represents the rounding computation.In formula , if u, vE, the computational formula of quantization coefficient Z is as follows:After getting u, v, QP) is the multiplier factor associated with QP. ≫ stands for binary right shift operation. f = 2qbits/n, n = 3 or 6, corresponding intraframe coding block and interframe coding block, respectively.Here, MF of an encoding block's E is equal to zero, it should be satisfied with the following conditions:If a quantized coefficient The sum of absolute difference (SAD) of the 4 × 4 subblock can be obtained by adding prediction error absolute value of each region. LetSo in the video coding standards based on the block-matching method, SAD is commonly used as the related function to measure the degree of correlation between the current encoding block and prediction block. The smaller value of SAD means there exiting stronger correlation between the two blocks, and they are more matchable. In this paper, the foreground translational region detection is on the basis of the of pixel region change detection theory .2) Translational MV Checking Formula. Let represents the position coordinates of the encoding block. SADx,y) is the pixel value of the current encoding block. c is the pixel value of the corresponding block in previous frame. M, N denote the partition dimensions of current encoding block, respectively.In formula ,  x,y) should be marked as 1.If the value of SADx,y) should be marked as 0.If the value of SAD3) Setting of Self-Adaptive Dynamic Threshold x,y)∈Sc Temporal Saliency Flowchart. In summary, the computational formula of temporal saliency analysis and detection is as follows:T = 3 means the current MV is MV noise;  T = 2 means the current encoding block is belongs to the foreground dynamic region;  T = 1 means the current encoding block is belongs to the foreground translational region; and  T = 0 means the current encoding block is in the background region. = 3, the current It should be pointed out that after filtering out the MV noise, The flow chart of temporal saliency detection is shown in Crr  in P frame encoding.HVS usually assigns higher visual importance to figures in foreground regions with abundant texture features and moving objects; therefore, those regions mentioned always select Intra 4 × 4 in I frame encoding or use subblock prediction mode Inter 8  in P frame encoding shown in .Although it is small probability event that using Intra mode in P-frame coding, once Intra mode is selected, means there appears new information or the encoding content is varied greatly in current frame compared with previous frame. It can be found that, in There is high consistency between prediction mode decision results and visual attention. Therefore, in the proposed algorithm, the prediction mode is regarded as spatial characteristic of visual perception analysis.According to the analysis above, current encoding frame can be sorted into spatial visual characteristic regions with different significance according to optimal prediction mode decision results. The spatial saliency detection computational formula is as follows:P, ModeI represent the optimal prediction modes selected by the current MB in P-frame and I-frame coding, respectively.ModeP ∈ {Intra}, means in P-frame coding, then Intra 4 × 4 or Intra 16 × 16 is selected as the optimal prediction mode, the spatial saliency is high, the current encoding block belongs to the human visual sensitive region, and it can be expressed as S = 2.If ModeP ∈ {Inter  8} or ModeI ∈ Intra  4 × 4, which means the current encoding block takes the subblock prediction mode  as the optimal prediction mode in P-frame coding or uses Intra  4 × 4 in I-frame coding, then the current encoding block has abundance of texture feature or changes in spatial domain, the current block belongs to attention region, the spatial saliency is high, and then it can be expressed as S = 1.If ModeP ∈ {Inter  16} or ModeI ∈ Intra  16 × 16, which means the current encoding block is smooth and belong to the visual nonsensitive region, then the spatial changes are slight, the current block has low spatial visual characteristics significance, it belongs to nonsignificant region, and it can be signed with S = 0.If ModeIn this paper, according to the spatiotemporal saliency detection results, we define video region of interest (VROI). LetThe computational formula can be expressed asT and S, the priority level of VROI is divided into 6 grades, from high to low being 5~0. For example, if the current MB uses Intra mode in P-frame coding  = 2), this means that the MB is in the visual sensitive region and has the highest visual attention; it can be signed with VRIO = 5, and so on.In this algorithm, according to the calculation number of The proposed algorithm framework is as depicted in In this paper, three existing algorithms are used to do the comparison experiment , 6, 7. TWe use 10 typical test sequences in multiple formats which include various types  of video with different scenes, motion, and flatness, separately, such as videos in daytime and nighttime, sports videos, news television, broadcast, and video surveillance.According to the visual perception characteristics analysis and the saliency detection procedure mentioned previously, the VROI marking results are shown in x, y, MV, Mode). The region with higher visual sensitive, the corresponding MB luminance value is higher. In In the output saliency detection results, the MB luminance values are proportional to the priority level of VRIO, ΔKLD are defined as follows formula in (In rmula in  and 19)C Time (%In In this paper, the interdependency between video encoding information and HVS characteristics is studied; it proposes a video saliency detection algorithm based on visual perception characteristics analysis and low-layer encoding information which can get from the bit-stream directly. The simulation results show that the proposed algorithm has better performance than other existing ones. It can filter out the motion vector noise, weaken the interference of translational motion vector and get rid of visual redundancy, and it can be used in the detection of visual perception characteristics analysis and saliency detection fast and effectively. The complication of the proposed algorithm is low, and its detection results are more consistent with HVS compared with other existing algorithms. It can be used conveniently in many Internet-based multimedia applications such as video retrieval based on ROI and video quality assessment. It can also be applied to video coding standards, such as HEVC and H.264/AVC.In the future, the various multimedia applications of the proposed video saliency detection algorithm combined with fast video coding technologies can realize fast video coding based on HVS for the latest video coding standard HEVC, and saliency detection technique can be taken as part of the video standard codec at medium-to-low bit-rates.


We tested predictors of interest in a clinical trial of naltrexoneplus counseling for heavy drinking reduction in young adults using a websurvey. Respondents could indicate interest in the clinical trial at theconclusion of the survey.N = 584, 60% female). Data were collected inOctober-November 2010.A random sample of university students completed the survey(n = 411), 22.6%(n =93) indicated interest. Equivalent levels ofinterest were found among past-year heavy drinkers. Non-white race andcurrent cigarette smoking predicted interest. Alcohol-related negativeconsequences score was a trend-level predictor in the full regression model,but a significant predictor in a reduced model.Among past-year drinkers (Non-white students, smokers and those with a high number of negativeconsequences may be more amenable to drinking reduction via medication andcounseling. These findings could facilitate efforts of researchers,administrators, counselors and other professionals to tailor drinkingreduction messages and facilitate treatment engagement byundergraduates. Heavy drinking among undergraduates is a major public health concern.According to the National Epidemiologic Survey on Alcohol and Related Conditions(NESARC), 31.3% of undergraduate, past-year drinkers reported two or moreheavy episodic drinking occasions per month and 16.7% reported two or moreoccasions per week . AlcoholAlthough heavy drinking and AUD rates are high, evidence suggests youngpeople are reticent to engage in mental health treatment in general and foraddictive behaviors, in particular. Based on analyses of NESARC data, Blanco et al. found thThe nature of the relationship between alcohol problem severity and treatmentinterest is unclear. Some studies have found that alcohol problem severity predictstreatment interest and help-seeking. Wells et al.  found thYoung adults may prefer interventions to reduce consumption and associatedharms rather than to promote outright abstinence , and eviThe opiate antagonist naltrexone may represent the best option forpharmacotherapy for alcohol use reduction . FindingResearchers have recognized that “finding methods to increasetreatment utilization and retention among emerging adults and adolescents is aresearch priority”  (p 400).Given the established efficacy of individual counseling and naltrexone, itwould be valuable to determine which characteristics are associated with interest ina clinical trial testing this combination of approaches. Given modest prescriptionrates for naltrexone , it is uAs in previous studies, alcohol use and negative consequences wereconsidered as possible predictors of interest. Several additional variables thathave been linked to greater problem drinking severity were also included as possiblepredictors of interest. These risk factors include male sex ; white Finally, smoking status and perceived peer alcohol use were included aspotentially important predictors of interest. Cigarette smoking has been related toan increased likelihood of problem drinking  and poorA web-based survey was conducted at a small, private university in theNortheastern United States. A random sample of 1,822 students was notified aboutan upcoming survey via an email from the university’s counseling office.The sex and academic class composition of the invited sample was commensurate with the student body atlarge. One week later, an email including the survey link was distributed. Acoupon for a free coffee was included, regardless of participation. Two reminderemails were sent in the 18 days the survey was open. Respondents were alsoenrolled in drawings for $25 (1 in 20 odds) and $500 (1 winner) gift cards.Respondents had to be at least 18 years old. During informed consent,respondents were notified that they could have their responses considered forpreliminary eligibility for a clinical trial testing “individualcounseling and an FDA-approved medication called naltrexone.” Thisstatement was reiterated at the end of the survey, followed by the statement“Participants in this study are compensated up to $470 in the course ofthe study.” The web address for the clinical trial was provided sostudents could obtain more information. This survey and clinical trial wereapproved by the Institutional Review Board (IRB) of the Yale University Schoolof Medicine and the survey was approved by the IRB of the university where thesurvey was conducted.alpha = 0.78). Participantswere asked to report whether or not they smoked cigarettes at least once perweek. Participants also reported whether or not they had used marijuana or otherillegal drugs at all in the past year and also whether they had usedprescription medication not as prescribed in the past year.Efforts were made to keep the survey brief to enhance response rates. Anumber of items concerned recent substance use. Past-year alcohol use wasmeasured with five items from question sets recommended by NIAAA . Two of alpha = 0.90). The survey also included demographic items, an item pertaining to current living situationand a binary, yes/ no item concerning current treatment for “emotionalor psychiatric difficulties.”Respondents also completed items concerning their perception of thetypical drinking quantity per occasion of three classes of peers: 1) theirfriends; 2) other, same aged male students and 3) other, same-aged femalestudents. Options for each item ranged from “0” to “20or more” drinks. An average of these three items was taken of students. In the full sample, men reported a mean of 4.19 drinks perdrinking day (SD = 4.54), with women reporting a mean of 2.47(SD = 2.45). Men reported a mean of 0.68 binge episodes perweek (SD = 1.22), with women reporting 0.31(SD = 0.69) binge episodes. Among past-year drinkers, meandrinks per drinking day was 5.85 (SD = 4.37) for men and 3.43(SD = 2.25) for women. Frequency of binge drinking per weekwas 0.97 (SD = 1.36) for men and 0.42 (SD =0.78) for women.Past year alcohol use was reported by 70.4%  = 10.44, p = 0.001. Amongnon-whites, 39% were past-year abstainers, compared to 24.6% ofwhites. There were also significant academic class differences,X2  = 51.59,p<0.001. Seniors were more likely to have beenpast-year drinkers (92.1%). In contrast, 56.2% of first-yearstudents were past-year drinkers. Sophomores and juniors were also more likelythan first-years to have consumed alcohol in the past year . There were no significant sex differences indrinker/abstainer status.There were several significant relationships between demographicvariables and past-year drinker/abstainer status. Racial groups (white versusnon-white) differed in past-year alcohol use, n = 411). Distributions for continuous variables wereexamined first. Transformations were utilized when skewness values were greaterthan 3, as was the case for drinks per drinking day, binge drinking, negativeconsequences and peer drinking norms. Correlations were examined to determinewhether any variables to be included in the logistic regression were stronglyrelated. The only such relationship was drinks per drinking day with frequencyof binge drinking, r = 0.62, p<0.001.While high, this correlation was under the 0.70 threshold thought to beindicative of concern regarding multicollinearity [Only past-year drinkers were included in the primary analyses(inearity .n = 93). Level of interest was equivalent among past-yearheavy drinkers : 23.2% (85 out of367 heavy drinkers). Quadratic terms for drinks per drinking day and frequencyof binge drinking were both non-significant predictors and thus were removedfrom the model, leaving only linear terms for these two variables. A logisticregression testing the full model, including all variables identified a priorias potential predictors of interest in the clinical trial  = 38.77,p = 0.001, and a non-significant Hosmer-Lemeshow [X2 = 5.73, p = 0.677. In the fullmodel, two variables were significant  and another was a trend-level predictor of clinical trialinterest   . No modep < 0.10, i.e., the reduced model) was also foundto provide a good fit to the data based on a chi-square goodness of fit test,X2  = 30.59,p<0.001, and a non-significant Hosmer-Lemeshowtest, X2  = 4.27,p = 0.640. In the reduced model, the negative consequencesscore was a significant predictor  = 7.18,p = 0.007; social consequences,X2  = 4.59,p = 0.032; and risky behaviors,X2  = 5.38,p = 0.016, were significantly related to interest in theclinical trial.Post-hoc chi-square analyses were conducted to test which negativeconsequences had significant relationships with interest in the clinical trial.Difficulty controlling alcohol consumption ,The present findings indicated greater interest in an alcohol reductionclinical trial involving pharmacotherapy and individual counseling amongundergraduates who were non-white, current smokers and who reported morealcohol-related negative consequences. Clinical trial interest was not significantlyrelated to alcohol consumption variables, perceived peer drinking norms, sex andpast-year drug use.Although non-white students reported greater interest in the clinical trial,they consumed less alcohol than whites, a finding that is consistent with priorstudies. For example, in the Monitoring the Future study, African-American highschool seniors reported less heavy episodic drinking than whites . Young mThe results of the current study also suggest that being a cigarette smokermay motivate treatment interest. Given evidence for reciprocal effects betweensmoking and alcohol use via several mechanisms , smokerThe finding that a higher number of negative consequences predicted interestin the treatment study supports prior findings of positive relationships betweenalcohol problem severity and an inclination toward behavior change in young adults,8,10. OtResults of this survey are valuable because they provide information aboutundergraduates’ openness to pharmacotherapy for alcohol use reduction. Youngadult heavy drinking is a considerable public health problem , motivatDue to the particularities of young adult heavy drinking and the challengesinherent in recruiting and retaining undergraduate drinkers in alcohol treatment andclinical trials, methods to engage this population are needed . SurveysOur desires to keep the survey brief precluded use of many establishedmeasures. Further, because monetary compensation is provided to participants in theclinical trial, our findings may not generalize to interest in programs offeringlittle or no remuneration . It is worth noting thoughthat the compensation was mentioned after the purpose and type of treatment weredescribed. The wording also stated that compensation was provided “in thecourse of the study,” making clear that payment would not be in a lump sum.The rate of interest expressed by survey respondents was probably higher than forother interventions, but was still reported by less than ¼ of past-yeardrinkers. This suggests that, although the compensation probably contributed tostudents’ interest, it was not enticing enough to attract a majority ofrespondents. Thus, it seems unlikely that many students without some intrinsicmotivation to change expressed interest in the trial due to the compensationalone.The survey response rate was low compared to traditional pencil and papersurveys, though comparable to several recent, web-based substance-related surveys inundergraduates offering comparable compensation –43. A weDespite these limitations, this study provides important information bearingon the public health concern of heavy drinking in undergraduates by identifyingpredictors of interest in a promising treatment. We hope the present report leads tosimilar reports of predictors of interest in a variety of treatment options andresearch studies aimed at alcohol reduction in young adults.The present study had a number of other strengths including a relativelylarge number of respondents and a stratified, random sample. Further, this study wasunique in that survey respondents who indicated interest in the trial wereessentially engaging in an action step toward behavior change because this stepinitiated contact from the study staff. Most prior studies regarding treatmentinterest and inclination have concerned retrospective reports of treatmentutilization ,7,11 and