A Novel Three-Point Modulation Technique for Fractional-N Frequency Synthesizer Applications

This paper presents a novel three-point modulation technique for fractional-N frequency synthesizer applications. Convention modulated fractional-N frequency synthesizers suffer from quantization noise, which degrades not only the phase noise performance but also the modulation quality. To solve this problem, this work proposes a three-point modulation technique, which not only cancels the quantization noise, but also markedly boosts the channel switching speed. Measurements reveal that the implemented 2.4 GHz fractional-N frequency synthesizer using three-point modulation can achieve a 2.5 Mbps GFSK data rate with an FSK error rate of only 1.4 %. The phase noise is approximately -98 dBc/Hz at a frequency offset of 100 kHz. The channel switching time is only 1.1 μs with a frequency step of 80 MHz. Comparing with conventional two-point modulation, the proposed three-point modulation greatly improves the FSK error rate, phase noise and channel switching time by about 10 %, 30 dB and 126 μs, respectively

Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

<p>Abstract</p> <p>Background</p> <p>Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.</p> <p>Results</p> <p>We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.</p> <p>Conclusion</p> <p>We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.</p

Crystal structures of γ-glutamylmethylamide synthetase provide insight into bacterial metabolism of oceanic monomethylamine

Monomethylamine (MMA) is an important climate-active oceanic trace gas and ubiquitous in the oceans. The γ-glutamylmethylamide synthetase (GmaS) catalyzes the conversion of MMA to γ-glutamylmethylamide (GMA), the first step in MMA metabolism in many marine bacteria. The gmaS gene occurs in ~23% of microbial genomes in the surface ocean and is a validated biomarker to detect MMA-utilizing bacteria. However, the catalytic mechanism of GmaS has not been studied due to the lack of structural information. Here, the GmaS from Rhodovulum sp. 12E13 (RhGmaS) was characterized, and the crystal structures of apo-RhGmaS and RhGmaS with different ligands in five states were solved. Based on structural and biochemical analyses, the catalytic mechanism of RhGmaS was explained. ATP is first bound in RhGmaS, leading to a conformational change of a flexible loop (Lys287-Ile305), which is essential for the subsequent binding of glutamate. During the catalysis of RhGmaS, the residue Arg312 participates in polarizing the γ-phosphate of ATP and in stabilizing the γ-glutamyl phosphate intermediate; Asp177 is responsible for the deprotonation of MMA, assisting the attack of MMA on γ-glutamyl phosphate to produce a tetrahedral intermediate; and Glu186 acts as a catalytic base to abstract a proton from the tetrahedral intermediate to finally generate GMA. Sequence analysis suggested that the catalytic mechanism of RhGmaS proposed in this study has universal significance in bacteria containing GmaS. Our results provide novel insights into MMA metabolism, contributing to a better understanding of MMA catabolism in global carbon and nitrogen cycles

Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. The hypersensitive analytical technique of proteomics can detect molecular changes before the tumor is palpable. The surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) is a newly-developed technique of evaluating protein separation in recent years. The protein chips have established the expression of tumor protein in the serum specimens and become the newly discovered markers for tumor diagnosis. The objective of this study was to find new markers of the diagnosis among groups of CRC, colorectal benign diseases (CBD) and healthy controls. The assay of SELDI-TOF-MS with analytical technique of protein-chip bioinformatics was used to detect the expression of protein mass peaks in the sera of patients or controls. One hundred serum samples, including 52 cases of colorectal cancer, 27 cases of colorectal benign disease, and 21 cases of healthy controls, were examined by SELDI-TOF-MS with WCX2 protein-chips.</p> <p>Results</p> <p>The diagnostic models (I, II and III) were setup by analyzed the data and sieved markers using Ciphergen - Protein-Chip-Software 5.1. These models were combined with 3 protein mass peaks to discriminate CRC, CBD, and healthy controls. The accuracy, the sensitivity and the particularity of cross verification of these models are all highly over 80%.</p> <p>Conclusions</p> <p>The SELDI-TOF-MS is a useful tool to help diagnose colorectal cancer, especially during the early stage. However, identification of the significantly differentiated proteins needs further study.</p

Endoscopic Submucosal Dissection for Gastric Epithelial Tumors: A Multicenter Study in Taiwan

Background/PurposeEndoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastric cancer (EGC). The purpose of this study was to determine the effectiveness and complications of ESD for gastric epithelial tumors in Taiwan.MethodsWe retrospectively analyzed the efficacy and outcome of ESD in patients who received ESD for gastric epithelial tumors between June 2004 and August 2007.ResultsA total of 70 patients with gastric epithelial tumors were treated by ESD. The mean age was 66.5 ±12.9 years (range, 35–84 years). The mean size of the gastric epithelial tumors was 1.85 ± 0.81 cm. The mean size of resected specimens was 3.26 ± 1.39 cm. The one-piece resection rate was 91.4% (64/70). The median operation time was 92.4 minutes. The complicating bleeding and perforation rates were 5.7% (4/70) and 4.3% (3/70), respectively. Emergency surgery was performed for three patients with perforations. The local recurrence rate of gastric cancer was 2.8%. Except for one patient who died of congestive heart failure and another who died of stroke, the remaining 68 patients (97.1%) survived.ConclusionESD is a promising local curative treatment option for EGC in Taiwan but it still carries risks of perforation and bleeding. The education and learning curve of endoscopists will improve the outcome of this procedure

Modification of atrioventricular node in a special condition treating paroxysmal supraventricular tachycardia

Modification of atrioventricular node is a usual and necessary operation to cure atrioventricular nodal reentrant tachycardia (AVNRT). In this operation, atrioventricular block is the most severe complication and its prevention is of our great concern. This complication always occurs under some special circumstances with potential risk. So, it is very important to realize such conditions, as in this paper. A patient with paroxysmal palpitation for 10 years, aggravating to shortness of breath with chest distress for 1 year; cardiac electrophysiological examination found slow conduction in both antegrade and retrograde paths of reentrant loop, and typical AVNRT could be induced. During effective ablation there was no junctional rhythm. In some special cases, modification of atrioventricular node should not only rely on the junctional rhythm to determine the ablation effect, but also on the time of cardiac electrophysiological examination, as such to avoid the severe complication of atrioventricular block caused by excessive ablation

Catalytically efficient Ni-NiOₓ-Y₂O₃ interface for medium temperature water-gas shift reaction

The metal-support interfaces between metals and oxide supports have long been studied in catalytic applications, thanks to their significance in structural stability and efficient catalytic activity. The metal-rare earth oxide interface is particularly interesting because these early transition cations have high electrophilicity, and therefore good binding strength with Lewis basic molecules, such as H2O. Based on this feature, here we design a highly efficient composite Ni-Y2O3 catalyst, which forms abundant active Ni-NiOx-Y2O3 interfaces under the water-gas shift (WGS) reaction condition, achieving 140.6 μmolCO gcat-1 s-1 rate at 300 °C, which is the highest activity for Ni-based catalysts. A combination of theory and ex/in situ experimental study suggests that Y2O3 helps H2O dissociation at the Ni-NiOx-Y2O3 interfaces, promoting this rate limiting step in the WGS reaction. Construction of such new interfacial structure for molecules activation holds great promise in many catalytic systems