State Variables of the Arm May Be Encoded by Single Neuron Activity in the Monkey Motor Cortex

Revealing the type of information encoded by neurons activity in the motor cortex is essential not only for understanding the mechanism of motion control but also for developing a brain-machine interface. Thus far, the concept of preferred direction vector (PD) has dominated the discussion regarding how neural activity encodes information; however, a unified view of exactly what information is encoded has not yet been established. In the present study, a model was constructed to describe temporal neuron activity by a dot product of the PD and the movement variables vector consisting of joint torque and angular velocity. The plausibility of this model was tested by comparing estimated neural activity with that recorded from the monkey motor cortex, and it was found that this model was able to explain the temporal pattern of neuron activity irrespective of its passive responsiveness. The mean determination coefficients of neurons that responded to proprioceptive stimuli and that responded to visual stimuli were relatively high values of 0.57 and 0.58, respectively. These results suggest that neurons in the monkey motor cortex encode state variables of the arm in a framework of modern control theory and that this information could be decoded for controlling a brain-machine interface

Adenovirus-mediated transfection of caspase-8 sensitizes hepatocellular carcinoma to TRAIL- and chemotherapeutic agent-induced cell death

AbstractCaspase-8 belongs to the cysteine protease family and is known to be activated at the initial step in the cascade of TRAIL-induced apoptosis. The activation of procaspase-8 can be blocked by a relatively large amount of c-FLIP, which renders resistance to death receptor-mediated apoptosis in many types of cancer cells. To ask if extrinsic over-expression of caspase-8 contributes to the induction of apoptosis, we introduced the caspase-8 gene into HCC cells using an adenoviral (Adv) vector (Adv-Casp8). We demonstrated that Adv-Casp8 increased expression of active forms of caspase-8 in MOI-dependent manner. A large amount of Adv-Casp8 (MOI of 50) induced apoptosis significantly in HCC cells and resulted in downregulation of c-FLIP (in SK-Hep1, HLE, and HepG2 cells), XIAP, survivin, and Bcl-xL (in HLE cells) and dynamic release of cytochrome c and Smac from the mitochondria into the cytosol. On the other hand, a small amount of Adv-Casp8 (MOI of 10) causes a slight but detectable increase in the level of apoptosis with only a small effect on anti-apoptotic proteins and mitochondrial activation. However, small amounts of Adv-Casp8 augmented TRAIL- or chemotherapeutic agent-induced cell death (with an MOI of 10 or 20, respectively). These results suggest both that exogenous over-expression of caspase-8 by Adv-Casp8 may be essential for induction of HCC cell death and that the combination of Adv-Casp8 and TRAIL or chemotherapeutic agents could provide a useful strategy for treatment of HCC

Progressing subglottic and tracheobronchial stenosis in a patient with CHARGE syndrome diagnosed in adulthood

AbstractA 33-year-old woman was admitted for a pseudocroup-like cough and wheezing after general anesthesia. Several months ago, she had undergone cardiac re-operation and turbinectomy, both of which had involved difficult intubations. Bronchoscopy indicated a pin-hall-like subglottic stenosis; therefore, emergency tracheotomy was performed. Six years later, a computed tomography scan demonstrated progressive stenosis of the entire circumference of the trachea and main bronchi. She died at 40 years. Her autopsy revealed marked tracheobronchial stenosis. She had many medical histories that had gone undiagnosed and had been clinically ill with only heart defects. She did not have coloboma but had microphthalmos, atresia choanae, retarded growth development, and deafness; thus, we diagnosed CHARGE syndrome that refers to multiple congenital anomalies, including airway abnormalities, which can lead to secondary complications such as traumatic stenosis after intubation. Physicians should have knowledge of this rare disease and should pay special attention to potential airway problems

Development and verification of control system for heat recovery ground source heat pump system

An operation method and control system for heat recovery ground source heat pump (HR-GSHP) systems have been developed. By applying the operation method and control system, the heating and cooling output from the respective GSHP units can be controlled according to the operational condition. This maximizes the energy saving effect by operating the GSHP units without excess temperature change of the heat carrier fluid. In this paper, the outlines of HR-GSHP system and the importance of control system for the HR-GSHP systems were firstly explained. Next, the control system's configuration and the control methodology were explained. In addition, the operation of a HR-GSHP system with the control system, in which the control methodology had been installed, was verified by using the field test apparatus. As the result, it was confirmed that the above control methodologies were applicable

A Study of Long-Term Metabolism of Nucleic Acid in the Repair Process of Cancer Cells with Cis-diamminedichloroplatinum (II)

CDDP is one of the anticancer drugs in which the presence of the repair mechanism has been pointed out. Thus, using established pulmonary cancer cells, we evaluated the metabolism of DNA and RNA in damaged cells treated with CDDP (0.1, 1.0, 10μg/ml) by means of 3 H-TdR . 3 H-UR incorporation assay for 15 days referring to the growth curve and colony forming assay. 3H-TdR uptake inhibition rate in CDDP treatment was higher than 3H-UR uptake inhibition rate and showed good correlation with the inhibition rate of colony formation. In order to evaluate the activity of metabolism of DNA and RNA, the experimental period was divided into two parts : an early stage (2-10 days) and a later stage (7-15 days), and changing phases of uptake of 3H-TdR and 3H-UR was estimated as an increased rate. In the early stage, cells treated CDDP at lower concentrations tended to show more active DNA and RNA metabolism, especially RNA. In the later stage, cells with 0.1μg/ml CDDP which had shown only slight growth inhibition in the early stage revealed lower activity than that in the early stage. Cells with 1.0vg/ml CDDP which showed regrowth after 7 days, and cells with 10μg/ml CDDP which were not recognized with proliferation were observed with more active metabolism of RNA than that in the early stage. Those results indicated that metabolism of RNA is closely associated with the cellular repair process by CDDP

Inhibition of GSK-3β activity attenuates proliferation of human colon cancer cells in rodents

The authors\u27 recent discovery that glycogen synthase kinase-3β (GSK-3β) participates in colon cancer cells\u27 survival and proliferation prompted us to investigate whether GSK-3β inhibition alters proliferation of colon cancer cells in vivo. Groups of four or five athymic mice (Balb/c, nu/nu) with subcutaneous xenografts of SW480 human colon cancer cells were treated with dimethyl sulfoxide (DMSO) or different doses (1, 2 and 5mg/kg body weight) of either small-molecule GSK-3β inhibitor (SB-216763 and AR-A014418) by intraperitoneal injection three times per week for 5 weeks. Compared with DMSO (a diluent of the GSK-3β inhibitors) as a control, either GSK-3β inhibitor significantly inhibited proliferation of cancer cell xenografts in the rodents in a dose-dependent manner. Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose-dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK-3β inhibitor. No adverse events or effects were observed in the rodents during the course of treatment, except for rare lethal accidents due to intraperitoneal injection. Morphological examination showed no apparent pathologic changes in major organs including the lungs, liver, pancreas, kidneys, spleen and large bowel of rodents treated with DMSO and the GSK-3β inhibitors. The results indicate that the GSK-3β inhibitors would be a novel class of therapeutic agent for colon cancer. © 2007 Japanese Cancer Association