Design of linear transmitters for wireless applications

Wireless standards for high data-rate communications typically employ complex modulation schemes that have large peak-to-average power ratios (PAPR), along with a significant bandwidth requirement. Transmitters for such applications often employ off-chip power amplifiers (PAs), that are typically operated in back-off, such that the peak output power is less than the output 1-dB compression point (P1dB), in order to minimize distortion. In mobile systems, architectures that can enhance the linearity of the transmit chain are highly attractive since these can reduce the PA's back-off requirement, which helps to enhance efficiency. In this dissertation, linearization techniques for mobile transmitters are explored. A Cartesian feedback-feedforward transmitter is proposed for linearity enhancement. The transmit path in the architecture is placed in a Cartesian feedback loop. The feedback error signal is applied to a Cartesian feedforward path for further linearity improvement. Linearity of the feedback-feedforward system is analyzed by using a Volterra series representation. System simulations using two-tone signals and modulated signals are also presented and are used to verify the linearity enhancement provided by the proposed architecture. A prototype transmitter IC that employs the Cartesian feedback-feedforward approach is implemented in a 0.13 μm CMOS process. Design considerations for critical transmitter circuits are discussed. A proof-of-concept Cartesian feedback-feedforward architecture that includes the prototype IC and external components is demonstrated. The implementation allows for a 8.7 dB improvement in the adjacent channel leakage ratio (ACLR), compared to an open-loop transmitter, for an output power of 16.6 dBm at 2.4 GHz while employing a 16-QAM LTE signal with 1.4 MHz bandwidth. The linearity of the Cartesian feedback-feedforward system is found to depend primarily on the loop gain of the Cartesian feedback and the linearity of the Cartesian feedforward path, which introduces a trade-off with power consumption. To enhance the linearity of the Cartesian feedback-feedforward transmitter even further within the Cartesian feedback loop, two modified Cartesian feedback-feedforward architectures are explored. System simulations show that both modified configurations can help to enhance linearity compared to the above Cartesian feedback-feedforward transmitter.Electrical and Computer Engineerin

LAP2 Is Widely Overexpressed in Diverse Digestive Tract Cancers and Regulates Motility of Cancer Cells

BACKGROUND: Lamina-associated polypeptides 2 (LAP2) is a nuclear protein that connects the nuclear lamina with chromatin. Although its critical roles in genetic disorders and hematopoietic malignancies have been described, its expression and roles in digestive tract cancers have been poorly characterized. METHODS: To examine the expression of LAP2 in patient tissues, we performed immunohistochemistry and real-time PCR. To examine motility of cancer cells, we employed Boyden chamber, wound healing and Matrigel invasion assays. To reveal its roles in metastasis in vivo, we used a liver metastasis xenograft model. To investigate the underlying mechanism, a cDNA microarray was conducted. RESULTS: Immunohistochemistry in patient tissues showed widespread expression of LAP2 in diverse digestive tract cancers including stomach, pancreas, liver, and bile duct cancers. Real-time PCR confirmed that LAP2β is over-expressed in gastric cancer tissues. Knockdown of LAP2β did not affect proliferation of most digestive tract cancer cells except pancreatic cancer cells. However, knockdown of LAP2β decreased motility of all tested cancer cells. Moreover, overexpression of LAP2β increased motility of gastric and pancreatic cancer cells. In the liver metastasis xenograft model, LAP2β increased metastatic efficacy of gastric cancer cells and mortality in tested mice. cDNA microarrays showed the possibility that myristoylated alanine-rich C kinase substrate (MARCKS) and interleukin6 (IL6) may mediate LAP2β-regulated motility of cancer cells. CONCLUSIONS: From the above results, we conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2β regulates motility of cancer cells and suggest that LAP2β may have utility for diagnostics and therapeutics in digestive tract cancers

LAP2β regulates migration of diverse digestive tract cancers cells.

<p>Boyden chamber assay (A-G) and wound healing assay (H, SNU638 cells) were used to measure migration of cancer cells. LAP2β siRNA significantly inhibited FBS- or EGF-induced migration compared to SCR siRNA in SNU638 (A, C), PANC1 (A, D) or other digestive tract cancer cells (G). Overexpression of LAP2β in SNU638 (B, E) or PANC1 (B, F) cells significantly increased migration compared to the control vector (B, E, F). EGF (100 ng/ml) or 10% FBS was used to induce chemotaxis. Mitomycin C (0.01 µg/ml) was added to remove effects of proliferation. Two days after transfection with 100 nM LAP2β siRNA or 100 nM scrambled (SCR) siRNA, both migration assays were performed. Four or six hours later after addition of EGF or FBS into Boyden chamber assay, cells were fixed. After a scratch in wound healing assay, migrated cells were fixed at the indicated times. Representative staining of migrated cells was presented (A, B). Migrated cells were counted and the data are presented as graphs (C-G). Data are the means±SD of three independent experiments in triplicate (C-G, *P<0.01, Student’s t-test).</p

Role of LAP2β in the proliferation of cancer cells.

<p>Western blotting (A, B) and real-time PCR (C, D) were used to determine the efficiency of knockdown (A, C) or overexpression (B, D) of LAP2β in SNU638 or PANC1 cells. Data are the means±SD of three independent experiments (*P<0.01, Student’s t-test). (E) Effect of LAP2β knockdown on proliferation of cancer cells. WST-1 assay was used to measure proliferation of cancer cells in the presence of 10% FBS. Five days after transfection with by 100 nM LAP2β siRNA or 100 nM scrambled (SCR) siRNA, WST-1 proliferation assay was performed. (F) Effect of LAP2β overexpression on proliferation of cancer cells. WST-1 assay was conducted in SNU638 or PANC1 cells overexpressing LAP2β gene or control vector. Data are the means±SD of three independent experiments in quintuplicate (*P<0.01, Student’s t-test).</p

LAP2β regulates invasion of gastric and pancreatic cancer cells.

<p>Matrigel invasion assay was used to measure invasion of cancer cells. Knockdown of LAP2β significantly inhibited FBS- and EGF-induced invasion compared to SCR siRNA in SNU638 (A, C) or PANC1 (A, D) cells. Overexpression of LAP2β in SNU638 (B, E) or PANC1 (B, F) cells significantly increased invasion compared to the control vector. EGF (100 ng/ml) or 10% FBS was used to induce invasion. Mitomycin C (0.01 µg/ml) was added to remove effects of proliferation. Two days after transfection with 100 nM LAP2β siRNA or 100 nM scrambled (SCR) siRNA, the invasion assays were performed. Representative staining of invaded cells was presented (A, B). Invaded cells were counted and the data are presented as graphs (C-F). Data are the means±SD of three independent experiments in triplicate (C-F, *P<0.01, Student’s t-test).</p

LAP2β enhances metastatic efficiency in a xenograft model.

<p>Gastric cancer cells overexpressing LAP2β gene or control vector were injected into spleen and metastasis to liver was examined 5 weeks later. Metastatic tumor regions were indicated by dotted circles. Representative immunostainings with anti-LAP2, anti-IL6, anti-STAT3, and anti-MARCKS antibodies, and H&E stainings in a liver metastasis are presented. Asterisk indicates tumor lesions. Scale bar, 50 µm.</p

LAP2β-induced change in gene expression.

<p>FC, fold change.</p

LAP2 is overexpressed in diverse digestive tract cancers.

<p>(A) Immunohistochemical staining showed overexpression of LAP2 in diverse digestive tract cancers including pancreas, liver, stomach and bile duct cancers. Note overexpression of LAP2 in metastatic cancer cells. Scale bar, 200 µm. (B) Overexpression of LAP2β in gastric cancer tissues was examined by real-time PCR using specific primers for the β-isoform. GAPDH was used to normalize all data.</p

LAP2β-induced gene expression.

<p>Gene expression between gastric cancer cells overepxressing LAP2β gene or control vectors were compared by cDNA microarray. Real-time PCR was used to confirm the LAP2β-induced change in gene expression of <i>MARCKS, STAT3 and IL-6</i> in SNU638 cells. The data are plotted as fold changes compared with mock cells. Data are the means±SD of three independent experiments in quintuplicate (*P<0.01, Student’s t-test).</p