Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglycerate kinase gene in females

Analysis of X-chromosome inactivation patterns in women has been used to assess the clonality of various tumors. In this report, we analyzed 27 liver tumors in women, including 18 samples obtained by the performance of ultrasonically guided thin-needle biopsies. By analysis of the heterogeneity of phosphoglycerate kinase gene, 11 of 27 (41%) cases were found to be heterozygous at the gene. Of these informative 11 cases with liver tumors, 7 cases were "large" tumors (> 25 mm in diameter) and 4 cases were "small" tumors (< 25 mm in diameter). All 7 large tumors showed monoclonal patterns by the phosphoglycerate kinase gene analysis. Of the 4 small tumors, 2 showed monoclonal, and 2 showed polyclonal patterns. The 2 with monoclonal patterns were pathologically diagnosed as hepatocellular carcinoma despite their small sizes (20 mm and 23 mm). Of the two with polyclonal patterns, the smallest one (15 mm) was diagnosed as benign adenomatous hyperplasia, and the other as hepatocellular carcinoma heavily infiltrated by lymphocytes. These data suggest that analysis of the methylation pattern of the phosphoglycerate kinase gene may be helpful on rare occasions in elucidating the nature of liver tumors but must in fact be used in conjunction with histological appearances to avoid errors secondary to inflammatory infiltrates.     

Global optimization methods for engineering applications: A review

A review of the methods for global optimization reveals that most methods have been developed for unconstrained problems. They need to be extended to general constrained problems because most of the engineering applications have constraints. Some of the methods can be easily extended while others need further work. It is also possible to transform a constrained problem to an unconstrained one by using penalty or augmented Lagrangian methods and solve the problem that way. Some of the global optimization methods find all the local minimum points while others find only a few of them. In any case, all the methods require a very large number of calculations. Therefore, the computational effort to obtain a global solution is generally substantial. The methods for global optimization can be divided into two broad categories: deterministic and stochastic. Some deterministic methods are based on certain assumptions on the cost function that are not easy to check. These methods are not very useful since they are not applicable to general problems. Other deterministic methods are based on certain heuristics which may not lead to the true global solution. Several stochastic methods have been developed as some variation of the pure random search. Some methods are useful for only discrete optimization problems while others can be used for both discrete and continuous problems. Main characteristics of each method are identified and discussed. The selection of a method for a particular application depends on several attributes, such as types of design variables, whether or not all local minima are desired, and availability of gradients of all the functions.Notation Number of equality constraints - () ^T A transpose of a vector - A A hypercubic cell in clustering methods - Distance between two adjacent mesh points - Probability that a uniform sample of sizeN contains at least one point in a subsetA ofS - A(v, x) Aspiration level function - A The set of points with cost function values less thanf(x _G ^* ) +. Same asA _f () - A _f () A set of points at which the cost function value is within off(x _G ^* ) - A () A set of points x with[f(x)] smaller than - A _N The set ofN random points - A _q The set of sample points with the cost function value f _q - _Q The contraction coefficient; –1 _Q 0 - _R The expansion coefficient; _E > 1 - _R The reflection coefficient; 0 < _R 1 - A _x () A set of points that are within the distance from x _G ^* - D Diagonal form of the Hessian matrix - det() Determinant of a matrix - d _j A monotonic function of the number of failed local minimizations - d _t Infinitesimal change in time - d _x Infinitesimal change in design - A small positive constant - (t) A real function called the noise coefficient - ₀ Initial value for(t) - exp() The exponential function - f ^(c) The record; smallest cost function value over X^(C) - [f(x)] Functional for calculating the volume fraction of a subset - Second-order approximation tof(x) - f(x) The cost function - An estimate of the upper bound of global minimum - f ^E The cost function value at x^E - f ^L The cost function value at x^L - f _opt The current best minimum function value - f ^P The cost function value at x ^P - f ^Q The cost function value at x ^Q - f _q A function value used to reduce the random sample - f ^R The cost function value at x ^R - f ^S The cost function value at x^S - f _{T F min} A common minimum cost function value for several trajectories - f _{TF opt} The best current minimum value found so far forf _{TF min} - f ^W The cost function value at x ^W - G Minimum number of points in a cell (A) to be considered full - The gamma function - A factor used to scale the global optimum cost in the zooming method - Minimum distance assumed to exist between two local minimum points - gi(x) Constraints of the optimization problem - H The size of the tabu list - H(x^*) The Hessian matrix of the cost function at x^* - h _j Half side length of a hypercube - h _m Minimum half side lengths of hypercubes in one row - I The unity matrix - ILIM A limit on the number of trials before the temperature is reduced - J The set of active constraints - K Estimate of total number of local minima - k Iteration counter - The number of times a clustering algorithm is executed - L Lipschitz constant, defined in Section 2 - L The number of local searches performed - _i The corresponding pole strengths - log () The natural logarithm - LS Local search procedure - M Number of local minimum points found inL searches - m Total number of constraints - m(t) Mass of a particle as a function of time - m() TheLebesgue measure of thea set - Average cost value for a number of random sample of points inS - N The number of sample points taken from a uniform random distribution - n Number of design variables - n(t) Nonconservative resistance forces - n _c Number of cells;S is divided inton _c cells - NT Number of trajectories - Pi (3.1415926) - P _i ^(j) Hypersphere approximating thej-th cluster at stagei - p(x ⁽ⁱ⁾⁾ Boltzmann-Gibbs distribution; the probability of finding the system in a particular configuration - pg A parameter corresponding to each reduced sample point, defined in (36) - Q An orthogonal matrix used to diagonalize the Hessian matrix - _i (i = 1, K) The relative size of thei-th region of attraction - r _i ^(j) Radius of thej-th hypersp here at stagei - R _x ^* Region of attraction of a local minimum x^* - r _j Radius of a hypersphere - r A critical distance; determines whether a point is linked to a cluster - R ⁿ A set ofn tuples of real numbers - A hyper rectangle set used to approximateS - S The constraint set - A user supplied parameter used to determiner - s The number of failed local minimizations - T The tabu list - t Time - T(x) The tunneling function - T _c (x) The constrained tunneling function - T _i The temperature of a system at a configurationi - TLIMIT A lower limit for the temperature - TR A factor between 0 and 1 used to reduce the temperature - u(x) A unimodal function - V(x) The set of all feasible moves at the current design - v(x) An oscillating small perturbation. - V(y⁽ⁱ⁾) Voronoi cell of the code point y⁽ⁱ⁾ - v^–1 An inverse move - v _k A move; the change from previous to current designs - w(t) Ann-dimensional standard. Wiener process - x Design variable vector of dimensionn - x^# A movable pole used in the tunneling method - x⁽⁰⁾ A starting point for a local search procedure - X^(c) A sequence of feasible points {x⁽¹⁾, x⁽²⁾,,x^(c)} - x(t) Design vector as a function of time - X^* The set of all local minimum points - x^* A local minimum point forf(x) - x^*(i) Poles used in the tunneling method - x _G ^* A global minimum point forf(x) - Transformed design space - The velocity vector of the particle as a function of time - Acceleration vector of the particle as a function of time - x ^C Centroid of the simplex excluding x ^L - x ^c A pole point used in the tunneling method - x ^E An expansion point of x ^R along the direction x ^C x ^R - x ^L The best point of a simplex - x ^P A new trial point - x ^Q A contraction point - x ^R A reflection point; reflection of x ^W on x ^C - x ^S The second worst point of a simplex - x ^W The worst point of a simplex - The reduced sample point with the smallest function value of a full cell - Y The set of code points - y ⁽ⁱ⁾ A code point; a point that represents all the points of thei-th cell - z A random number uniformly distributed in (0,1) - Z ^(c) The set of points x where [f ^(c) – ] is smaller thanf(x) - []₊ Max (0,) - | | Absolute value - The Euclidean norm - f[x(t)] The gradient of the cost function     

Handling of radioactive wastes formed outside the nuclear fuel cycle

Conclusions The system of regional specialized industrial plants "Radon" was created more than 30 years ago and over this time it has made it possible to utilize radioactive wastes from industrial and scientific centers in the country. The technology adopted by the specialized industrial plants for preparing and burying radioactive wastes makes possible safe localization of the wastes for a long period of time. Investigations designed to estimate the effect of the points of burial by the specialized industrial plants on environmental objects showed that the technical solutions adopted are reliable. At the present time the system of regional specialized industrial plants is experiencing difficulties on the legislative, financial, and technical levels. The system must be reconstructed and modernized. The basis for future decisions will be determined by the legislative base and the principles which are employed in the process. The optimal path toward modernization of the regional industrial groups is to produce complexes based on them for collecting, processing, and temporary storage of radioactive wastes formed within the service zone. The Moscow Scientific and Industrial Association "Radon" is now implementing this concept. Moscow Scientific and Industrial Association "Radon." Translated from Atomnaya énergiya, Vol. 79, No. 6, pp. 437–443, December, 1995.     

Spatial performance with perspective displays as a function of computer graphics eyepoint elevation and geometric field of view

The purpose of this study was to investigate the effect of varying the elevation of the computer graphics eyepoint and the geometric field of view on judgements of spatial information using a stereoscopic perspective display. Twelve subjects judged the elevation and azimuth angle separating two computer-generated objects viewed using an eyepoint elevation that ranged between -15 degrees and 45 degrees and a geometric field of view that ranged between 40 degrees and 80 degrees. The results of the study indicated that judgements of elevation were affected by the compression of the vertical axis resulting from the raised eyepoint elevation. Furthermore, azimuth judgements were influenced by both the eyepoint elevation and the geometric field of view. Implications of the results for the design of displays and for spatial performance using stereoscopic displays are discussed.     

Radical surgery and conservation of erection in Peyronie's disease

The radical surgical option we propose for Peyronie's disease consists in removing the sclero-hyanolitic focus (plaque) and replacing it by an autologous dermal graft taken from the upper outer thigh area. Between 1981 and 1994, we operated 564 patients with Induration penis plastica (IPP), 418 of whom underwent plaque excision and dermal grafting. All could be assessed at two-year follow-up. Two main complications were observed: penile flexure relapse (71 Pts, 17% of cases), and erectile dysfunction with decreased corporal rigidity (84 Pts, 20% of cases). A mild deviation of the penis can occur some months after surgery and it is not due to disease progression (as it should have evolutive characteristics) but is mere scar retraction (44 Pts, 76% of examined relapsed flexures). The degree of this graft retraction is linked to the individual's histologic response and can be due to an idioptic tissular response or to an insufficient size of the patch. In some cases, the post-op penile flexure can result from a progression of disease (14 Pts, 24% of examined relapses flexures) and can be due either to a new "focus" or to an incomplete removal of the previous plaque. As the patient will date the onset of a possible postoperative erectile deficit from the time of the operation, it is advisable to assess preoperatively the real erectile ability of all patients. Furthermore, a post-op impaired erectile response (84 Pts, 20%) could result from a subalbuginear fibrosis of the erectile tissue that leads to a caverno-occlusive dysfunction (60%). In more than 35% of patients we found a psychogenic component, due to post-surgical stress, that involves an adrenergic hypertone with peripherical vasoconstriction. In few cases (4%) the post-op erectile dysfunction is the consequence of peroperative arterial damages that results in hypoaesthesia of the glans (injury of dorsal arteries) or in failure to obtaining corporal rigidity (damage of cavernosal arteries). A review of our experience involving plaque excision and dermal grafting led us to propose this option in case of mechanical disturbance during coitus and when the association of erectile dysfunction can be excluded.     

Learning of sequential movements in the monkey: process of learning and retention of memory

1. To characterize procedural learning and memory, we devised a behavioral paradigm that allows us to examine the process of learning of new procedures, repeatedly and without serious difficulties for primate subjects. We trained two monkeys to perform a sequential button press task. Upon pressing of a home key, 2 of 16 (4 x 4 matrix) light-emitting diode (LED) buttons (called "set") were illuminated simultaneously, and the monkey had to press them in a predetermined order that he had to find out by trial-and-error. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial; an error at any set aborted the trial. A given hyperset was repeated as a block of experiment until 20 successful trials were performed. Monkeys PI and BO experienced 313 and 92 hypersets, respectively. Most of these hypersets were experienced only once (1 block of experiment); the others (28 hypersets for monkey PI and 14 hypersets for monkey BO) were chosen for extensive practice. 2. The learning, indicated as the decrease in the number of trials to criterion and the decrease in the performance time, proceeded at three levels: 1) short-term and sequence-selective learning that occurred by repeating a particular hyperset during a block of experiment; our monkeys learned, to some degree, to perform a new hyperset within a short period (< 5 min); 2) long-term and sequence-selective learning that took place for each hyperset across days; by daily practice, they further improved their skills for performing the particular hyperset; and 3) long-term and sequence-unselective learning that was indicated by the improvement of performance for new hypersets; the monkeys were required to learn many hypersets, each just once (a block of trials), in which they performed gradually better with more experiences in the 2 x 5 task. 3. To examine whether the memory was retained for a long period, we had the monkey learn 12 hypersets sufficiently, then we stopped the training and retested them after 1 or 6 mo. After the 1-mo interruption the performance was significantly better than that for new hypersets. After the 6-mo interruption the performance was not different from new hypersets in terms of the number of trials but was significantly better than new hypersets in terms of the performance time. The results suggest that motor memory (measured by performance time) can be retained longer than procedural memory (measured by the number of trials).     

Modeling of magnesium diffusion in gallium arsenide. 2. Redistribution of ion-implanted impurity

The redistribution of ion-implanted magnesium under high-rate annealing conditions is calculated. Consideration of the nonuniformity of the interstitial gallium atom distribution makes it possible to explain ascending diffusion in the region of strong distortions of a crystalline lattice.Belarusian State University of Information Science and Radioelectronics, Minsk, Belarus. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 68, No. 1, pp. 39–43, January–February 1995.     

Significant reduction of medical costs by differentiation therapy with all-trans retinoic acid during remission induction of newly diagnosed patients with acute promyelocytic leukemia. The Japan Adult Leukemia Study Group

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.