A scalable manufacturing process for flexible active‐matrix e‐paper displays

Abstract— A scalable manufacturing process for fabricating active‐matrix backplanes on low‐cost flexible substrates, a key enabler for electronic‐paper displays, is presented. This process is based on solution processing, ink‐jet printing, and laser patterning. A multilayer architecture is employed to enable high aperture ratio and array performance. These backplanes were combined with E Ink electrophoretic media to create high‐performance displays that have high contrast, are bistable, and can be flexed repeatedly to a radius of curvature of 5 mm.     

Interval Arithmetic on Multimedia Architectures

In this paper, we show how to implement interval arithmetic on multimedia architecture extensions. Due to the difficulties that current architectures have with the directed rounding modes the speed-up is rather modest. The study, nevertheless, may be helpful in future design of hardware extensions for interval arithmetic.     

Dissociation of memory retrieval and search processes: an event-related fMRI study

A cognitive task can often be subdivided into several subprocesses, which follow a specific temporal order. Here, we report an event-related functional magnetic resonance imaging (fMRI) experiment on memory search, in which the temporal onset of search in primary memory was varied relative to retrieval from secondary memory. Furthermore, previous behavioral studies demonstrated that search times in primary memory depend on the number of items in a memory set, whereas retrieval from secondary memory is a set-size independent process. We analyzed the dependency of the blood oxygenation level dependent (BOLD)-response on the temporal onset of memory search on the one hand and on memory set size on the other hand to differentiate the contribution of retrieval from secondary memory, maintenance in primary memory, item search in primary memory, and response-related processes. The timing of activation followed cue presentation bilaterally in the middle frontal gyri (Brodmann area (BA) 9,46) and the inferior parts of the precentral gyri (BA6). In all other regions of interest (ROI), supplementary motor area (SMA), posterior parietal cortex, antero-superior insula, and primary motor cortex, the onset of activation was delayed with delayed probe presentation, ruling out participation in retrieval from secondary memory. The amplitude of the BOLD-response increased with increasing memory set size in all ROI except primary motor cortex and left posterior parietal cortex. All areas with cue-associated BOLD onset, suggesting involvement in retrieval, showed prolonged BOLD activation, suggesting that they also support maintenance of the retrieved information.     

Microstructure and properties of a composite system for dental applications composed of glass-ceramics in the SiO2–Li2O–ZrO2–P2O5 system and ZrO2-ceramic (TZP)

The objective of the study was to develop a biocompatible composite system which was composed of TZP-ceramic (tetragonal zirconia polycrystals, ZrO₂ stabilized with 3 mol% Y₂O₃) and two glass-ceramics of the SiO₂–Li₂O–ZrO₂–P₂O₅ type. The metal-free composite system would satisfy the translucency, the biocompatibility and the strength requirements of dentistry. The two glass-ceramics of the SiO₂–Li₂O–ZrO₂–P₂O₅ type with a content of 15 and 20 wt% ZrO₂ respectively, were chemically and physically adapted to TZP-ceramic. The glass-ceramics were used as a dentin buildup material. The TZP-ceramic had the function of a root post. The shape of the post was cylindrical with a conical tip. The composite system was easy to process through viscous flow of the glass-ceramic at 900 and 1000°C, respectively. The microstructure and the mechanical properties of two glass-ceramics of the SiO₂–Li₂O–ZrO₂–P₂O₅ type were examined therefore.     

In vitro antitumor activity of the novel marine agent, ecteinascidin-743 (ET-743, NSC-648766) against human tumors explanted from patients

BACKGROUND: Ecteinascidin-743 (ET-743), a member of the ecteinascidin family selected for clinical development, is a tetrahydroisoquinolone alkaloid isolated from the marine ascidian, Ecteinascidia turbinata. This novel compound is a minor groove binding, guanine-specific alkylating agent which also interacts with the microtubule network and blocks cell cycle progression at late S/G2. MATERIALS AND METHODS: A soft agar cloning assay was used to determine the in vitro effects of ET-743 against primary human tumor specimens taken directly from patients. A total of 93 evaluable specimens were exposed to ET-743 for one-hour (n = 25) and/or 14-day continuous exposure (n = 92) at concentrations ranging from 0.1 nM to 1 microM. In vitro responses were defined as an inhibition > or = 50% of human tumor colony forming units at a given concentration. RESULTS: One-hour exposure to ET-743 at concentrations of 0.1 nM, 1 nM, 10 nM, 100 nM and 1 microM induced in vitro responses in 0% (0/17), 6% (1/17), 16% (4/25), 13% (1/8), and 25% (2/8) of specimens, respectively. Continuous exposure to ET-743 at concentrations of 0.1 nM, 1 nM, 10 nM, 100 nM and 1 microM, inhibited 0% (0/16), 13% (2/16), 49% (44/90), 62% (47/76), and 77% (58/75) of tumor specimens, respectively. Tumor-specific responses and concentration-dependent relationships were observed with a continuous exposure to ET-743. At 100 nM, the compound inhibited 79% (11/14) breast, 69% (9/13) non-small-cell lung, 58% (7/12) ovary, and 88% (7/8) melanoma specimens. At 1 microM, ET-743 inhibited 100% (14/14) breast specimens, 85% (11/13) non-small-cell lung, 67% (8/12) ovary and 86% (6/7) melanoma specimens. Activity of ET-743 at and above 10 nM was also observed against sarcoma and kidney tumors. At 10 nM concentration and continuous exposure ET-743 demonstrated incomplete cross-resistance with paclitaxel, alkylating agents, doxorubicin and cisplatin. CONCLUSIONS: Our data from the cloning assay indicate that the duration of exposure to ET-743 is an important factor in human tumors. Therefore, long-term exposure to ET-743 may be preferred in future clinical trials. The activity of ET-743 in breast, non-small-cell lung, and ovarian cancers as well as in melanoma may deserve further clinical evaluations. The potential of ET-743 in sarcoma and renal tumors might also be considered. In addition, our data indicate that a plasma concentration of 100 nM of ET-743 must be considered as a target during the clinical development of the compound; also the concept of continuous/protracted exposure in clinical trials with ET-743 has to be taken into account.     

Meta-analysis of multiple outcomes by regression with random effects

Earlier work showed how to perform fixed-effects meta-analysis of studies or trials when each provides results on more than one outcome per patient and these multiple outcomes are correlated. That fixed-effects generalized-least-squares approach analyzes the multiple outcomes jointly within a single model, and it can include covariates, such as duration of therapy or quality of trial, that may explain observed heterogeneity of results among the trials. Sometimes the covariates explain all the heterogeneity, and the fixed-effects regression model is appropriate. However, unexplained heterogeneity may often remain, even after taking into account known or suspected covariates. Because fixed-effects models do not make allowance for this remaining unexplained heterogeneity, the potential exists for bias in estimated coefficients, standard errors and p-values. We propose two random-effects approaches for the regression meta-analysis of multiple correlated outcomes. We compare their use with fixed-effects models and with separate-outcomes models in a meta-analysis of periodontal clinical trials. A simulation study shows the advantages of the random-effects approach. These methods also facilitate meta-analysis of trials that compare more than two treatments.     

Growth-associated synthesis of recombinant human glucagon and human growth hormone in high-cell-density cultures of Escherichia coli

Synthesis of two recombinant proteins (human glucagon and human growth hormone) was investigated in fed-batch cultures at high cell concentrations of recombinant Escherichia coli. The glucose-limited growth was achieved without accumulation of metabolic by-products and hence the cellular environment is presumed invariable during growth and recombinant protein synthesis. Via exponential feeding in the two-phase fed-batch operation, the specific cell growth rate was successfully controlled at the desired rates and the fed-batch mode employed is considered appropriate for examining the correlation between the specific growth rate and the efficiency of recombinant product formation in the recombinant E. coli strains. The two recombinant proteins were expressed as fusion proteins and the concentration in the culture broth was increased to 15 g fusion growth hormone 1(-1) and 7 g fusion glucagon 1(-1). The fusion growth hormone was initially expressed as soluble protein but seemed to be gradually aggregated into inclusion bodies as the expression level increased, whereas the synthesized fusion glucagon existed as a cytoplasmic soluble protein during the whole induction period. The stressful conditions of cultivation employed (i.e., high-cell-density cultivation at low growth rate) may induce the increased production of various host-derived chaperones and thereby enhance the folding efficiency of synthesized heterologous proteins. The synthesis of the recombinant fusion proteins was strongly growth-dependent and more efficient at a higher specific growth rate. The mechanism linking specific growth rate with recombinant protein productivity is likely to be related to the change in cellular ribosomal content.     

Vitamin E supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits

The effects of vitamin E supplementation in a dose of 450 mg/1000 g chow on the myointimal proliferation of the abdominal aorta after balloon injury were studied in 4 groups of rabbits (24 each). The animals were fed regular diet, regular diet plus vitamin E, 1% cholesterol-enriched diet, and 1% cholesterol-enriched diet plus vitamin E. Each animal underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 8 balloon-injured and 8 sham-operated animals of each group, the abdominal aortas were harvested 3 days after the procedure for the analysis of prostacyclin and thromboxane A2 synthesis, thiobarbituric acid reactive substances (TBARS) levels, enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GP) as well as reduced (GSH) and oxidized (GSSG) glutathione levels, 3H-thymidine uptake, cholesterol as well as vitamin E contents. In the other 8 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for the morphometric study. In dependent of high cholesterol feeding, the vitamin E-treated rabbits had lower aortic production of thromboxane B2, higher 6-keto-PGF1 alpha and higher 6-keto-PGF1 alpha/thromboxane B2 ratios in both procedures. The aortic TBARS levels of the rabbits treated high cholesterol alone were significantly higher than the other three groups in both procedures. Balloon injury had a trend to increase TBARS levels and had significantly higher 3H-thymidine uptake (each p < 0.001) than sham operation in each group. Vitamin E supplement to high cholesterol diet or regular chow reduced aortic TBARS levels (p < 0.005 and 0.01, respectively) and 3H-thymidine uptake (p < 0.05 and 0.01, respectively), as well as attenuated myointimal proliferation of the abdominal aorta and left common iliac artery after balloon injury; but only supplement to high cholesterol diet reached statistical significances (both p < 0.05 compared to rabbits fed high cholesterol alone). These results suggest that vitamin E supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation of the abdominal aortic wall, thus attenuates myointimal proliferation after balloon injury; these presentations are particularly obvious in diet-induced hypercholesterolemic rabbits.     

Effects of induced hypertension on transcranial Doppler ultrasound velocities in patients after subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage. METHODS: Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of > 15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation. RESULTS: In 10 of 19 patients (53%), TCD velocities changed by > 15% and paralleled changes in mean arterial pressure. This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%). Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation. CONCLUSIONS: In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood flow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage.     

Regulation of periodontal ligament cell functions by interleukin-1beta

Periodontal ligament (PDL) cells maintain the attachment of the tooth to alveolar bone. These cells reside at a site in which they are challenged frequently by bacterial products and proinflammatory cytokines, such as interleukin-1beta (IL-1beta), during infections. In our initial studies we observed that IL-1beta down-regulates the osteoblast-like characteristics of PDL cells in vitro. Therefore, we examined the functional significance of the loss of the PDL cell's osteoblast-like characteristics during inflammation. In this report we show that, during inflammation, IL-1beta can modulate the phenotypic characteristics of PDL cells to a more functionally significant lipopolysaccharide (LPS)-responsive phenotype. In a healthy periodontium PDL cells exhibit an osteoblast-like phenotype and are unresponsive to gram-negative bacterial LPS. Treatment of PDL cells with IL-1beta inhibits the expression of their osteoblast-like characteristics, as assessed by the failure to express transforming growth factor beta1 (TGF-beta1) and proteins associated with mineralization, such as alkaline phosphatase and osteocalcin. As a consequence of this IL-1beta-induced phenotypic change, PDL cells become responsive to LPS and synthesize proinflammatory cytokines. The IL-1beta-induced phenotypic changes in PDL cells were transient, as removal of IL-1beta from PDL cell cultures resulted in reacquisition of their osteoblast-like characteristics and lack of LPS responsiveness. The IL-1beta-induced phenotypic changes occurred at concentrations that are frequently observed in tissue exudates during periodontal inflammation (0.05 to 5 ng/ml). The results suggest that, during inflammation in vivo, IL-1beta may modulate PDL cell functions, allowing PDL cells to participate directly in the disease process by assuming LPS responsiveness at the expense of their normal structural properties and functions.