Development of a 100keV electron beam nano lithography system

A wide range energy (25, 50, 100keV) electron beam lithography system with ZrO/W Schottky electron source and UHV chamber has been developed. The electron probe stability of 2.5%/hour is measured, and a beam diameter of 3nm is confirmed at 100keV beam energy. The ultimate pressure of bakeable work chamber is confirmed to reach 4×10⁻¹⁰Torr. With the UHV chamber and a gas jet nozzle, this system allows to perform in-situ electron beam nanolithography by combining with UHV multichamber systems.     

Mathematical modelling of prostate cancer growth and its application to hormone therapy

Hormone therapy in the form of androgen deprivation is a major treatment for advanced prostate cancer. However, if such therapy is overly prolonged, tumour cells may become resistant to this treatment and result in recurrent fatal disease. Long-term hormone deprivation also is associated with side effects poorly tolerated by patients. In contrast, intermittent hormone therapy with alternating on- and off-treatment periods is a possible clinical strategy to delay progression to hormone-refractory disease with the advantage of reduced side effects during the off-treatment periods. In this paper, we first overview previous studies on mathematical modelling of prostate tumour growth under intermittent hormone therapy. The model is categorized into a hybrid dynamical system because switching between on-treatment and off-treatment intervals is treated in addition to continuous dynamics of tumour growth. Next, we present an extended model of stochastic differential equations and examine how well the model is able to capture the characteristics of authentic serum prostate-specific antigen (PSA) data. We also highlight recent advances in time-series analysis and prediction of changes in serum PSA concentrations. Finally, we discuss practical issues to be considered towards establishment of mathematical model-based tailor-made medicine, which defines how to realize personalized hormone therapy for individual patients based on monitored serum PSA levels.     

Analysis and stabilization for networked linear hyperbolic systems of rationally dependent conservation laws

In this paper, for a networked linear hyperbolic partial differential equations (PDEs) system of conservation laws, the propagation periods of which are rationally dependent, with coupled boundary conditions, we propose a novel approach to analyze its controllability and observability. In addition, we propose a design method of a stabilizing controller, where a boundary-input with boundary-valued feedback is considered. First, we characterize the control properties, such as controllability of such a PDE system, in terms of the corresponding ones of a finite-dimensional discrete-time system defined on the boundaries of the PDE system, which is derived by fully exploiting the method of characteristics. Since the obtained discrete-time system is low-dimensional, its analysis is relatively easier. Next, we propose a design method of a stabilizing controller based on this discrete-time system. Finally, numerical simulations are presented to show that the proposed method is effective.     

Duality of rate coding and temporal coding in multilayered feedforward networks

A functional role for precise spike timing has been proposed as an alternative hypothesis to rate coding. We show in this article that both the synchronous firing code and the population rate code can be used dually in a common framework of a single neural network model. Furthermore, these two coding mechanisms are bridged continuously by several modulatable model parameters, including shared connectivity, feedback strength, membrane leak rate, and neuron heterogeneity. The rates of change of these parameters are closely related to the response time and the timescale of learning.     

Self-organization of orientation-selective and ocular-dominance maps through spike-timing-dependent plasticity

In the primary visual cortex, there are orientation-selective and ocular-dominance maps. These maps correlate with each other. Although many models have been proposed which explain the formation of the orientation-selective map and the ocular-dominance map, these models contain a physiologically implausible process. It is indicated that spike-timing-dependent plasticity (STDP) can yield a “topographic map” without any constraints. We show that large STDP time constants yield the orientation-selective map, and small STDP time constants yield the ocular-dominance map. This result suggests that the relationship between the orientation-selective and the ocular-dominance maps can be explained by the modulation of STDP time constants.     

Rewiring-induced chaos in pulse-coupled neural networks

The dependence of the dynamics of pulse-coupled neural networks on random rewiring of excitatory and inhibitory connections is examined. When both excitatory and inhibitory connections are rewired, periodic synchronization emerges with a Hopf-like bifurcation and a subsequent period-doubling bifurcation; chaotic synchronization is also observed. When only excitatory connections are rewired, periodic synchronization emerges with a saddle node-like bifurcation, and chaotic synchronization is also observed. This result suggests that randomness in the system does not necessarily contaminate the system, and sometimes it even introduces rich dynamics to the system such as chaos.     

Mucin carbohydrate antigens (T, Tn, and sialyl-Tn) in human ovarian carcinomas: relationship with histopathology and prognosis

Altered glycosylation of mucins leading to the expression of T, Tn, and sialyl-Tn antigens has been shown in ovarian carcinoma, but its relationship with prognosis is still unclear. We investigated immunohistochemically the expression of these antigens in 38 (17 serous and 21 mucinous) ovarian carcinomas to assess their potential prognostic value as compared with stage of disease, histopathology of tumors, and survival time of patients. Eight benign ovarian tumors (four serous and four mucinous), and four normal ovarian tissues also were studied. Of the 38 carcinomas, 25 (66%) expressed T, 27 (71%) expressed Tn, and 33 (87%) expressed sialyl-Tn antigens. Most cases (83%) expressed two or all of the three types of antigens simultaneously. Normal ovarian epithelia showed no staining for these antigens, and benign ovarian tumors were either negative or occasionally expressed weak staining in less than 25% of epithelial cell areas. Statistical analyses showed strong associations between Tn and sialyl-Tn antigen expressions and disease stage as well as histological grade. In 19 ovarian carcinoma patients with available survival data, the overall survival times of patients with high Tn or sialyl-Tn antigen expression were significantly worse than those of the patients with negative and low expression (P < .05 and P < .01). In multivariate stepwise regression analysis, disease stage (P = .000) and Tn antigen expression (P = .02) were found to be significant independent parameters associated with the overall survival time. These findings suggest that, with exception of T antigen expression, the expression of Tn and sialyl-Tn antigens in ovarian carcinomas may provide additional prognostic information on patient outcome.     

Spontaneous regression of localized neuroblastoma detected by mass screening

PURPOSE: A retroperitoneal access is commonly used for open urological procedures. Since the introduction of the balloon dissecting technique by Gaur this anatomical route has also been used for laparoscopic surgery. We present our experience with retroperitoneoscopy in 200 cases. MATERIALS AND METHODS: From December 1992 to October 1997 a total of 200 retroperitoneoscopic procedures were performed in 197 patients 4 to 82 years old, comprising 78 nephrectomies, 50 renal cyst resections, 14 nephropexies, 11 ureterolyses, 8 retroperitoneal lymph node dissections, 8 renal biopsies, 6 adrenalectomies, 6 heminephrectomies, 6 pyeloplasties, 5 ureterolithotomies, 6 ureterocutaneostomies and 2 others. Of the patients 38 (19%) and 22 (11%) had undergone previous abdominal surgery, and kidney and ureter operations, respectively. Dissection of the retroperitoneal space was enabled by the use of a balloon catheter in 14, balloon trocar system in 93 and finger dissection technique in 93 cases. RESULTS: We classified 76 procedures (38%) as simple (renal biopsy, renal cyst resections, ureterocutaneostomy), 102 (51%) as difficult (adrenalectomy, nephrectomy, nephropexy) and 22 (11%) as very difficult (pyeloplasty, heminephrectomy, lymphadenectomy). There was a significant learning curve during the first 50 cases reflected by longer operating time, and higher complication, conversion to open surgery and open reintervention rates (14, 10 and 6%, respectively). In addition to the learning curve, mean operating time depended on the difficulty of the procedure, averaging 45 to 100 minutes for a simple, 95 to 185 for a difficult and 185 to 240 for a very difficult retroperitoneoscopy. In the last 50 cases the complication, conversion and reintervention rates (2, 4 and 2%, respectively) were acceptable for routine clinical application. CONCLUSIONS: After experience with more than 200 cases of retroperitoneoscopy the access technique has been significantly simplified. The procedure is standardized, safe and reproducible.     

Combination of an actor/critic algorithm with goal-directed reasoning

In this paper, we propose an actor/critic algorithm combined with goal-directed reasoning. The actor/critic algorithm has been considered to be a model of the basal ganglia in the brain. However, the basal ganglia also appear to contribute to goal-directed reasoning. Thus, we study goal-directed reasoning in the framework of the actor/critic algorithm and discuss its neural substrates. First, since goal-directed reasoning is realized by repeatedly setting subgoals, we consider setting a subgoal to be anaction, and incorporated it into the actor/critic algorithm. Next, two additional mechanisms, the rejection of bad subgoals and double learning, are introduced to improve the performance of the new algorithm. As a consequence, goal-directed reasoning is successfully combined with the actor/critic algorithm, and the performance of the actor/critic algorithm is improved by this combination. It is also shown that a hierarchical control structure appears during the learning process and disappears after the learning has been repeated many times.