Analysis and Design of CMOS Radio-Frequency Power Amplifiers

The continuous advancement of semiconductor technologies, especially CMOS technology, has enabled exponential growth of the wireless communication industry. This explosive growth in turn has completely changed people’s lives. The CMOS feature size scale down greatly benefits digital logic integrations, which result in more powerful, versatile, and economical digital signal processing. Further research and development has pushed analog, mixed-signal, and even radio-frequency (RF) circuit blocks to be implemented and integrated in CMOS. Future generations of wireless communication call for even further level of integration, and as of now, the only circuit block that is rarely integrated in CMOS along with other parts of the system is the power amplifier (PA). Due to the fact that the PA in a wireless communication system is the most power-hungry circuit block, the integration of RF PA in CMOS would potentially not only save the cost of the wireless communication system real estate, but also reduce power consumption since die-to-die connection loss can be eliminated. RF PA design involves handling large amounts of voltage and current at the radio frequencies, which in the present wireless communication standards are in the range of giga-hertz. Therefore, a good understanding of many aspects related to RF PA design is necessary. Theoretical analysis of the communication system, nonlinear effects of the PA, as well as the impedance matching network is systematically presented. The analysis of the nonlinear effects proposes a formal mathematical description of the multitone nonlinearity, and through its relationship with two-tone test, the proposed PA design methodology would greatly reduce the design time while improving the design accuracy. A thorough analysis of the available architecture and design techniques for efficiency and linearity enhancement of RF PA shows that despite tremendous amounts of research and development into this topic, the fundamental tradeoff between the two still limits the RF PA implementation largely within SiGe, GaAs, and InP technologies. A RF PA for Wideband Code-Division Multiple Access (WCDMA) application standard is proposed, designed, and implemented in CMOS that demonstrates the proposed segmentation technique that resolved the main tradeoff between power efficiency and linearity. The innovative architecture developed in this work is not limited to applications in the WCDMA communication protocol or the CMOS technology, although CMOS implementation would take advantage of the readily available digital resources

Nutritional requirements of <i>P</i>. <i>falciparum</i> concerning essential backbone moieties.

<p>Note: the presence of orthophosphate and S-adenosylmethioninamine in the same medium is not allowed. When <i>P</i>. <i>falciparum</i> grows on orthophosphate and S-adenosylmethioninamine as the only sources of phosphate and purines, it cannot synthesize enough ATP. The ATP limitation impedes the production of other phosphorylated nucleotides, sugar nucleotides, sphingomyelin and phospholipids in the stoichiometrically required amounts. As suggested throughout the manuscript, these metabolic processes are thermodynamically dependent (more details in the <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005397#pcbi.1005397.s001" target="_blank">S1 Methods</a>).</p

Reconstruction workflow for ToxoNet1 summarized as a flowchart illustration.

<p>Reconstruction workflow for ToxoNet1 summarized as a flowchart illustration.</p

Comparison of the number of metabolites, reactions and genes between the models for <i>T</i>. <i>gondii</i> and <i>P</i>. <i>falciparum</i>.

<p>Abbreviations: e—extracellular space, c—cytosol, m—mitochondrion, a—apicoplast, n—nucleus, er—endoplasmic reticulum, g—Golgi complex, v—digestive vacuole, im—mitochondrial intermembrane space.</p><p>Comparison of the number of metabolites, reactions and genes between the models for <i>T</i>. <i>gondii</i> and <i>P</i>. <i>falciparum</i>.</p

Composition of the minimal <i>in silico</i> media that allows ToxoNet1 to simulate replication of <i>T</i>. <i>gondii</i>.

<p>Abbreviations: FAD—flavine-adenine dinucleotide, NAD—nicoticamide-adenine dinucleotide, NADP—NAD phosphate, TPP—thiamine pyrophosphate, SAM—S-adenosyl-methionine, THF—tetrahydrofolate.</p><p>Composition of the minimal <i>in silico</i> media that allows ToxoNet1 to simulate replication of <i>T</i>. <i>gondii</i>.</p

Generation of an inducible ACL knockdown in ACSko parasites.

<p>(A) Schematic representation of the U1 snRNP-mediated ACL gene silencing with Cre-recombinase dependent positioning of U1 in Ku80ko wildtype and ACSko parasites. (B) PCRs performed on genomic DNA extracted from Ku80ko, ACL-lox, ACSko/ACL-lox validating integration of the pKI-ACL-3TyLox3’UTRLoxU1 construct to knock down ACL in the different strains. The sequences of the primers can be found in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004261#pcbi.1004261.s008" target="_blank">S7 Table (C and D)</a>. Immuno-blot of total lysates from ACL-lox, ACSko/ACL-lox where ACL-lox was integrated in the ACSko strain or ACS was knocked out in ACL-lox. Both independent lines show increased levels of ACL when ACS is absent. Western blot was performed using anti-Ty antibodies. Anti-TgProfilin (Prf) represents a loading control.</p

Gene essentiality predictions of ToxoNet 1 and available literature evidence.

<p>(NA denotes the cases when neither supporting nor contradicting literature reference could be found). Gene essentiality in <i>P</i>. <i>falciparum</i> is based on the Supplementary Table 1 of the review manuscript [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004261#pcbi.1004261.ref038" target="_blank">38</a>].</p><p>Gene essentiality predictions of ToxoNet 1 and available literature evidence.</p

Both ACS and ACL are dispensable in the tachyzoite stage of <i>T</i>. <i>gondii</i>.

<p>(A) Schematic representation of the two pathways to produce acetyl-CoA in the cytosol of <i>T</i>. <i>gondii</i>. Abbreviations: AcCoA, acetyl-CoA; α-KG, α-ketoglutarate; Cit, citrate; Glc, glucose; Lac, lactate; Mal, malate; OAA, oxaloacetic acid; Pyr, pyruvate; Suc, succinate. Enzymes in red: ACL, ATP-citrate lyase; ACS, Acetyl-CoA synthetase. (B) Scheme of the knock-in strategy used to introduce a 3Ty-tag in the endogenous loci of ACS, ACL and AT1. (C) Localization of endogenous ACS, ACL and AT1 C-terminally Ty-tagged (ACS-3Ty, ACL-3Ty and AT1-3Ty) in the cytoplasm, cytosol and endoplasmic reticulum respectively of intracellular parasites using anti-Ty as well as anti-GAP45 that stains the periphery and DAPI which stains the nucleus of the parasite. (D) Immuno-blot of total lysates from Ku80ko parasites expressing the C-terminally Ty-tagged endogenous ACS, ACL and AT1 proteins by Western blot using anti-Ty antibodies. Anti-Profilin (Prf) represents a loading control. (E) Schematic representation of the direct knockout strategy by double homologous recombination where ACS was replaced by the chloramphenicol resistance cassette and ACL by the HXGPRT selection cassette. The position of the primers used to confirm the integration and the length of the PCR products are indicated. PCRs performed on genomic DNA extracted from Ku80ko, ACSko and ACLko strains confirm the integration of the selection cassette and loss of the corresponding gene locus. The sequences of the primers can be found in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004261#pcbi.1004261.s008" target="_blank">S7 Table</a>. (F) Plaque assays performed with Ku80ko, ACSko and ACLko parasite lines fixed after 7 days. No significant defect in the lytic cycle could be observed. (G) Intracellular growth assay performed on Ku80ko, ACSko and ACLko strains by determining the number of parasites per vacuole 24h post infection. Data are represented as mean ± SD from 3 biological replicates.</p

Nutritional requirements of <i>T</i>. <i>gondii</i> predicted <i>in silico</i>.

<p>Required precursors:</p><p>¹—phenylalanine or phenylpyruvate;</p><p>²—folic acid or its derivatives;</p><p>³—l-2-aminoadipate 6-semialdehyde;</p><p>⁴–3-methyl-2-oxobutanoic acid;</p><p>⁵–4-methyl-2-oxopentanoate;</p><p>⁶ –(s)-3-methyl-2-oxopentanoic acid;</p><p>⁷—l-homocysteine;</p><p>⁸—phenylpyruvate;</p><p>⁹—a source of purine moiety: hypoxanthine, adenine, adenosine or similar;</p><p>¹⁰—pantothenate or valine+β-alanine;</p><p>¹¹—riboflavin;</p><p>¹²—nicotinic acid or its derivatives;</p><p>¹³—thiamine;</p><p>¹⁴–4-hydroxybenzoate;</p><p>¹⁵—an undefined”sulfur donor” molecule;</p><p>¹⁶—lipoic acid;</p><p>¹⁷—choline;</p><p>¹⁸—myo-inositol.</p><p>Nutritional requirements of <i>T</i>. <i>gondii</i> predicted <i>in silico</i>.</p

ACS and ACL are dually essential.

<p>(A) Following transfection of ACL-lox and ACSko/ACL-lox with Cre recombinase, excision and repositioning of U1 is followed by genomic PCRs over several culture passages (every 48h) using primers P17/P18 as depicted in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004261#pcbi.1004261.g004" target="_blank">Fig 4A</a> (P0, extracellular parasites 48h after Cre transfection; P1, extracellular parasites passaged once ~96h post transfection; P2, extracellular parasites passaged twice ~140h post transfection). (B) Histogram showing percentage of excised parasites over several passages (every 48h) in ACL-lox and ACSko/ACL-lox populations following transfection with Cre recombinase. Excised parasites were visualized by IFA looking for loss of ACL-3Ty signal. Due to fluctuation in transfection efficiency, data from one biological replicate is shown and represents mean ± SD from 3 technical replicates. 3 biological replicates were done and gave the same results. (P0, intracellular parasites 30h after Cre transfection; P1, intracellular parasites passaged once ~72h post transfection; P2, intracellular parasites passaged twice ~100h post transfection). (C) Immunofluorescence assay confirms the loss of ACL-3Ty and parasite pellicle integrity in a subset of vacuoles 30h following transfection of ACL-lox and ACSko/ACL-lox strains with a Cre recombinase expressing plasmid. IFAs were stained using anti-Ty, anti-GAP45 (Pellicle), anti-5F4 (mitochondrion) or anti-Atrx1 (apicoplast) antibodies and DAPI (nucleus). Arrowheads highlight nuclear and mitochondrial material lost in the vacuolar space and loss of the apicoplast due to loss of pellicle integrity.</p