A 322 MHz random-cycle embedded DRAM with high-accuracy sensing and tuning

A 16 Mb embedded DRAM macro in a fully CMOS logic compatible 90 nm process with a low noise core architecture and a high-accuracy post-fabrication tuning scheme has been developed. Based on the proposed techniques, 61% improvement of the sensing accuracy is realized. Even with the smallest 5 fF/cell capacitance, a 322 MHz random-cycle access while 32 ms data retention time which contributes to save the data retention power down to 60 /spl mu/W are achieved.     

A case of macrocystic cervical neurinoma diagnosed by MRI with Gd-DTPA

The authors report a rare case of a large cystic cervical neurinoma. A 45-year-old female was admitted to our clinic because of motor weakness of the right upper extremity, numbness of the right fingers and right posterior cervical pain. Metrizamide CT myelography demonstrated the outline of a low density mass. MRI showed a mass revealing low signal intensity on T1-weighted image, high signal intensity on T2-weighted image and marginal enhancement on contrast image with Gd-DTPA. The mass which was diagnosed as cystic tumor, was located in the intradural extramedullary space between C4 to C5 segments. After C4 through C5 laminectomy, the tumor was found to originate from the C5 anterior motor root. The tumor consisted mostly of a cystic part with a very thin solid compartment beneath the capsule. Postoperative course of the patient was uneventful. Although spinal neurinoma is one of the most common spinal tumors, an almost completely degenerated large cystic spinal neurinoma is extremely rare. MRI with Gd-DTPA was useful for the diagnosis of the cystic neurinoma by clearly enhancing the margin of the tumor.     

Nigrofrontal dopaminergic function as assessed by 18F-dopa PET

The existence of the nigrofrontal dopaminergic pathway has been demonstrated in neuroanatomical studies. We evaluated the presynaptic nigrofrontal dopaminergic function using 18F-dopa (FD) positron emission tomography (PET). The multiple time PET data in the frontal cortex from 20 to 70 min post-injection for FD were evaluated by Patlak analysis using the cerebellar time-activity curve as an input function. The frontal FD uptake rate constants could not be determined in 5 of 12 normal volunteers because of large deviations in the plots. There were no significant differences between the subjects among whom the frontal FD uptake rate constants could or could not be determined regarding the amount of FD injected, the frontal 18F counts, or whether or not they were pretreated with carbidopa. The uptake constants were determined in 9 or 12 patients with parkinsonian syndrome. While the mean (+/- S.D.) uptake constants in patients with Parkinson's disease (2.89 +/- 0.06 x 10(-3), n = 4) and in patients with progressive supranuclear palsy (2.81 +/- 0.10 x 10(-3), n = 3) were not significantly different from those in the normal volunteers (2.93 +/- 0.14 x 10(-3)), those in two patients with corticobasal degeneration (2.42 and 2.46, respectively) decreased in comparison to the control values. Differences in the nigrofrontal presynaptic dopaminergic function as assessed by FD-PET may explain the different pathogenesis and also help to differentiate between corticobasal degeneration and other parkinsonian syndromes, such as Parkinson's disease and progressive supranuclear palsy.     

Effects of Environmental Temperature and Compression Energy on Polymorphic Transformation During Tabletting

The effects of temperature on the polymorphic transformation and the compression of chlorpropamlde forms A and C during tabletting were investigated by X-ray diffractometry. The X-ray diffraction profiles of the sample powders deagglomerated after compression were recorded to calculate the degree of polymorphic transformation. A single punch eccentric tabletting machine equipped with two load cells (upper and lower punches) and with a noncontact displacement transducer was used to measure the compression stress, energy and distance between punches. A heater and a liquid nitrogen pool were mounted on the die of the tabletting machine, and the die temperature was controlled with a thermocontroller. Two types of compression methods, multi-tabletting at room temperature and single tabletting at 0-45°C, were used in the present study. In the first method, the stable form A or metastable form C was loaded in to the die and the sample was compressed with a compression stress of 196 MPa. Compression was repeated from 1 to 30 times. The results for forms A and C suggested that both forms were mutually transformed, and that the content of forms A and C reached equilibrium above 100 J/g of compression energy after more than 10-times compression. After 30-times compression, the content of A, C, and the noncrystalline solid form were almost constant at about 45%, 25% and 30%, respectively. The compression energy was estimated to be 500-600 J/g. In the second method, single tabletting at 0° and 45°C, the amount of form C transformed from form A at 45°C was about two times larger than that at 0°C at the same compression energy. The amount of form A transformed from form C at 45°C was almost the same as that transformed at 0°C. This suggests that the mechanochemical stability of form A was affected by compression temperature, while that of form C was independent of temperature. The crushing strength (CS) of from A tablet was about two times higher than that of form C even at the same porosity. The relationships between log (CS) of form A tablets compressed at 0 or 45°C and porosity showed straight lines with the same slope, but the slope for form C tablets compressed at 45°C was smaller than that for those compression at 0°C. From these results it appears that the transformation mechanism of forms A and C during compression was as follows: Form A or C was converted to a noncrystalline solid by mechanical energy, and then the solid was transformed into form A or C. The transformation of every form was affected by the environmental temperature.     

A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth

Cripto-1 is a member of the EGF-CFC/FRL1/Cryptic family and is involved in embryonic development and carcinogenesis. We designed a novel anti-Cripto-1 artificial antibody and assessed the recognition to the antigen and the potential to suppress the growth of cancer stem cells. First, single chain antibody clones were isolated by bio-panning with the affinity to recombinant Cripto-1 protein from our original phage-display library. Then, the variable regions of heavy chain VH and light chain VL in each clone were fused to constant regions of heavy chain CH and light chain CL regions respectively. These fused genes were expressed in ExpiCHO-S cells to produce artificial humanized antibodies against Cripto-1. After evaluation of the expression levels, one clone was selected and the anti-Cripto-1 antibody was produced and purified. The purified antibody showed affinity to recombinant Cripto-1 at 1.1 pmol and immunoreactivity to cancer tissues and cell lines. The antibody was available to detect the immunoreactivity in tissue microarrays of malignant tumors as well as in Cripto-1 overexpressing cells. Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC₅₀ at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.