Effective multi-objective inverse lithography technology at full-field and full-chip levels with a hybrid dynamic priority algorithm.

Inverse lithography technology (ILT), such as source mask optimization (SMO), is used to improve lithography performance. Usually, a single objective cost function is selected in ILT, and an optimal structure for one field point is achieved. The optimal structure is not the case for other images at full field points where the aberrations of the lithography system are different, even in high-quality lithography tools. The optimal structure that must match the high-performance images at the full field is urgently required for extreme ultraviolet lithography (EUVL). In contrast, multi-objective optimization algorithms (MOAs) limit the application of multi-objective ILT. Assigning target priority is incomplete in current MOAs, which results in the over-optimization of some targets and under-optimization of others. In this study, multi-objective ILT and a hybrid dynamic priority (HDP) algorithm were investigated and developed. High-performance images with high fidelity and high uniformity were obtained at multi-field and multi-clip areas across the die. A hybrid criterion was developed for the completion and reasonable prioritization of each target to ensure sufficient improvement. Compared to the current MOAs, the uniformity of images at full-field points was improved by up to 31.1% by the HDP algorithm in the case of multi-field wavefront error-aware SMO. The multi-clip source optimization (SO) problem showed the universality of the HDP algorithm to deal with different ILT problems. It acquired higher imaging uniformity than existing MOAs, which indicated that the HDP is more qualified for multi-objective ILT optimization than existing MOAs.

The effects of vitamin C on DDP-induced anemia in rats.

The aim of this study was to investigate the effects of vitamin C on cisplatin (DDP)-induced anemia and explore its possible mechanisms in rats. Adult male Sprague-Dawley rats were randomly divided into six groups: control, vitamin C 50, vitamin C 100, DDP, DDP plus vitamin C 50 and DDP plus vitamin C 100-treated groups. DDP was intravenous injected as a single dose and vitamin C was administered by gavage. Serum erythropoietin (Epo), hemoglobin (Hb) and blood urea nitrogen (BUN) concentration were measured 4 and 14 days after DDP treatment. The changes of renal tissue were examined by light microscope. Administration of DDP to rats induced anemia and nephrotoxicity, characterized with a significant decrease in serum Epo and Hb and increase in BUN concentrations. Pathological examination revealed that DDP caused significant renal damage in rats. Vitamin C administration produced amelioration in biochemical indices of anemia and nephrotoxicity and in histological change when compared to group DDP alone; concurrent administration of vitamin C at doses of 100 mg/kg being more effective. Results from this study indicate that the novel natural antioxidant vitamin C might have protective effect against DDP-induced anemia in rats.

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets.

BACKGROUND: To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. RESULTS: We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. CONCLUSIONS: SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.

[Influence of siRNA interfering ß-catenin on tumorigenicity in vivo of K562 cell line].

The aim of this study was to investigate the effects of ß-catenin on the tumorigenicity of K562 cells in vivo. The ß-catenin expression in K562 cells was down-regulated through sequence-specific siRNA, and the treated K562 cells were implanted into BALB/c nude mouse subcutaneously. And the tumor-forming rate and tumor-forming curve (interference group) were observed. Experiments were divided into 3 group: interference group (implanted K562 cells transfected with ß-catenin interfering plasmid DNA), control group (implanted K562 cells transfected with unrelated sequence plasmid DNA) and untreated group (implanted K562 cells transfected without plasmid DNA). The results indicated that the tumor-forming rates of untreated group (n = 9), control group (n = 8) and interference group (n = 9) were 100%, 87.5% and 0% respectively. The tumor-forming rate of interference group was significantly lower than those of the other 2 groups (p < 0.001). Comparison of the tumor-forming curve between 3 groups, showed that in first 2 groups existed tumor-forming and their final tumor volumes were almost the same, but the tumor growth of untreated group was faster than that in control group; while in the interference group there was not tumor-forming. It is concluded that the ß-catenin expression level in K562 cells is down-regulated through the interference of sequence-specific siRNA, thus affecting their tumor-forming potential in vivo.

Single-trial analysis of cortical oscillatory activities during voluntary movements using empirical mode decomposition (EMD)-based spatiotemporal approach.

This study presents a method based on empirical mode decomposition (EMD) and a spatial template-based matching approach to extract sensorimotor oscillatory activities from multi-channel magnetoencephalographic (MEG) measurements during right index finger lifting. The longitudinal gradiometer of the sensor unit which presents most prominent SEF was selected on which each single-trial recording was decomposed into a set of intrinsic mode functions (IMFs). The correlation between each IMF of the selected channel and raw data on other channels were created and represented as a spatial map. The sensorimotor-related IMFs with corresponding correlational spatial map exhibiting large values on primary sensorimotor area (SMI) were selected via spatial-template matching process. Trial-specific alpha and beta bands were determined in sensorimotor-related oscillatory activities using a two-spectrum comparison between the spectra obtained from baseline period (-4 to -3 s) and movement-onset period (-0.5 to 0.5 s). Sensorimotor-related oscillatory activities were filtered within the trial-specific frequency bands to resolve task-related oscillatory activities. Results demonstrated that the optimal phase and amplitude information were preserved not only for alpha suppression (event-related desynchronization) and beta rebound (event-related synchronization) but also for profound analysis of subtle dynamics across trials. The retention of high SNR in the extracted oscillatory activities allow various methods of source estimation that can be applied to study the intricate brain dynamics of motor control mechanisms. The present study enables the possibility of investigating cortical pathophysiology of movement disorder on a trial-by-trial basis which also permits an effective alternative for participants or patients who can not endure lengthy procedures or are incapable of sustaining long experiments.

ViTa: prediction of host microRNAs targets on viruses.

MicroRNAs (miRNAs) are involved in various biological processes by suppressing gene expression. A recent work has indicated that host miRNAs are also capable of regulating viral gene expression by targeting the virus genomes. To investigate regulatory relationships between host miRNAs and related viruses, we present a novel database, namely ViTa, to curate the known virus miRNA genes and the known/putative target sites of human, mice, rat and chicken miRNAs. Known miRNAs are obtained from miRBase. Virus data are collected and referred from ICTVdB, VBRC and VirGen. Experimentally validated miRNA targets on viruses were derived from literatures. Then, miRanda and TargetScan are utilized to predict miRNA targets within virus genomes. ViTa also provides the virus annotations, virus-infected tissues and tissue specificity of host miRNAs. This work also facilitates the comparisons between subtypes of viruses, such as influenza viruses, human liver viruses and the conserved regions between viruses. Both textual and graphical web interfaces are provided to facilitate the data retrieves in the ViTa database. The database is now freely available at http://vita.mbc.nctu.edu.tw/.

miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes.

Recent work has demonstrated that microRNAs (miRNAs) are involved in critical biological processes by suppressing the translation of coding genes. This work develops an integrated database, miRNAMap, to store the known miRNA genes, the putative miRNA genes, the known miRNA targets and the putative miRNA targets. The known miRNA genes in four mammalian genomes such as human, mouse, rat and dog are obtained from miRBase, and experimentally validated miRNA targets are identified in a survey of the literature. Putative miRNA precursors were identified by RNAz, which is a non-coding RNA prediction tool based on comparative sequence analysis. The mature miRNA of the putative miRNA genes is accurately determined using a machine learning approach, mmiRNA. Then, miRanda was applied to predict the miRNA targets within the conserved regions in 3'-UTR of the genes in the four mammalian genomes. The miRNAMap also provides the expression profiles of the known miRNAs, cross-species comparisons, gene annotations and cross-links to other biological databases. Both textual and graphical web interface are provided to facilitate the retrieval of data from the miRNAMap. The database is freely available at http://mirnamap.mbc.nctu.edu.tw/.