Linear Transduction Research Articles

Parametric magnon transduction to spin qubits.

The integration of heterogeneous modular units for building large-scale quantum networks requires engineering mechanisms that allow suitable transduction of quantum information. Magnon-based transducers are especially attractive due to their wide range of interactions and rich nonlinear dynamics, but most of the work to date has focused on linear magnon transduction in the traditional system composed of yttrium iron garnet and diamond, two materials with difficult integrability into wafer-scale quantum circuits. In this work, we present a different approach by using wafer-compatible materials to engineer a hybrid transducer that exploits magnon nonlinearities in a magnetic microdisc to address quantum spin defects in silicon carbide. The resulting interaction scheme points to the unique transduction behavior that can be obtained when complementing quantum systems with nonlinear magnonics.

A Review of Eigen-Mode and Frequency Control in Piezoelectric MEMS Resonators.

Piezoelectric MEMS resonators possess favorable properties such as strong electromechanical coupling, high Q, and polarized linear transduction, making them ideal for various applications including timing, sensing, and RF communication. However, due to process nonidealities and temperature variations, these resonators characteristics may deviate from their designed frequency and resonant eigenmode, requiring careful compensation for stable and precise operation. Furthermore, certain devices like gyroscopic resonators have two eigenmodes that need to be adjusted for frequency proximity and cross-mode coupling. Therefore, mode shape manipulation can also be important in piezoelectric resonators and will be another focus of this paper. Techniques for frequency and eigenmode control are classified into device- or system-level tuning, trimming, and compensation. This paper will compare and discuss the effectiveness of these techniques in specific applications to provide a comprehensive understanding of frequency and eigenmode control in piezoelectric MEMS resonators, aiding the development of advanced MEMS devices for diverse applications.

A Novel RPS19-Edited Hematopoietic Stem Cell Model of Diamond-Blackfan Anemia for Development of Lentiviral Vector Gene Therapy

Diamond-Blackfan anemia (DBA) is a congenital hypoplastic anemia that typically manifests in infancy as macrocytic anemia with reticulocytopenia. About 80% of DBA cases are caused by heterozygous loss-of-function mutations or deletions in one of 23 ribosomal proteins (RP) genes, with RPS19 being affected in ~25% of patients. Current therapies are suboptimal, and it is difficult to obtain DBA patient hematopoietic stem and progenitor cells (HSPCs) in sufficient quantity for preclinical development of new therapies. To address this gap, we used CRISPR/Cas9-edited healthy donor CD34 + HSPCs to create a novel model of RPS19-mutated DBA and used this model to develop an efficient RPS19-encoding lentiviral vector (LV) for gene therapy.Healthy donor CD34 + HSPCs were electroporated with ribonucleoprotein (RNP) complex consisting of Cas9 and guide RNAs (gRNAs) targeting RPS19 or the AAVS1 locus as a negative control, then grown in medium to support erythroid differentiation. All gRNAs analyzed generated high-frequency on-target insertion-deletion (indels) mutations (Fig. A). RPS19 indels specifically declined over time, suggesting that RPS19 disruption impairs cell proliferation and/or survival. To rescue the defect, we constructed a third-generation, self-inactivating LV expressing RPS19+GFP (RPS19/GFP LV). Transduction was optimized using poloxamer and prostaglandin E2 and linear transduction efficiency was noted even at high multiplicity of infection (MOI) (Fig. B). An MOI of 20 was used for subsequent experiments. In methylcellulose medium, RPS19 RNP-treated cells generated 72% fewer burst forming unit-erythroid (BFU-E) colonies compared to AAVS1 RNP-treated control cells. RPS19/GFP LVs with three different promoters (EF1α short, EF1α long and MND) partially restored BFU-E formation similarly (Fig. C); the EF1α short promoter was chosen for subsequent experiments due its track record for clinical use. We down-titrated the RNP concentration to generate a total indel frequency of ~25%, which resulted in approximately equal frequencies of RPS19 +/+ and RPS19 +/- BFU-E colonies. RPS19 -/- colonies were detected only after edited HSPCs were rescued by RPS19/GFP LV, due to lethality of this genotype (Fig. D). Transfection of CD34 + HSPCs with RPS19 RNP caused a 49% reduction in cell number after 14 days of liquid culture in erythroid differentiation medium compared to control HSPCs; this was corrected by treatment with RPS19/GFP LV (Fig. E). RPS19 RNP treatment of CD34 + HSPCs had no effect on the expansion of cells grown under myeloid differentiation conditions (Fig. F).We analyzed RNP-treated CD34 + cells further by transducing them with RPS19/GFP LV or control LV encoding GFPalone, transplanting them into immunodeficient NSGW mice and analyzing human donor cell progeny in mouse bone marrow after 16 weeks. In cells treated with AAVS1 RNP and GFP LV, the indel frequency dropped from 27.2±1.5% (SD) at 72 hours after editing (input) to 15.5±4.4% at 16 weeks post-transplant (43% reduction) (Fig. G). In HSPCs treated with RPS19 RNP and GFP LV the indel frequency dropped from 20.9±3.1% in input cells to 1.8±0.9% after 16 weeks (Fig. G) (92% reduction). In contrast, the indel frequency of donor HSPCs treated with RPS19 RNP and RPS19/GFP LV dropped from 23.6±2.7% in input cells to 8.4±1.6% (64% reduction), which represents a 5-fold increase in indel frequency compared to treatment with control GFP LV (p< 0.01)(Fig. G). In flow cytometry-purified, donor HSPC-derived myeloid, B-lymphocyte, HSPC and erythroid lineages at 16 weeks after xenotransplantation, the mean indel rates were 1.3% to 2.5% in cells derived from HSPCs treated with RPS19 RNP and GFP LV. Indel rates ranged from 6.9% to 9.2% in the progeny of input HSPCs that were rescued by RPS19/GFP LV, representing a 4-6-fold increase compared to transduction with control GFP LV (p<0.01) (Fig. H).In summary, our studies show that Cas9-mediated disruption of RPS19 in CD34 + HSPCs causes a selective erythroid defect in RPS19 +/- cells, recapitulating the canonical DBA defect. Additionally, deficient bone marrow repopulation by RPS19 +/- cells suggests an HSC defect, consistent with pancytopenia that is observed in many older DBA patients. The optimized RPS19 LV transduces HSPCs at high efficiency and alleviates both defects, supporting its potential utility for DBA therapy. [Display omitted] DisclosuresYen: Beam Therapeutics: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Weiss: Beam Therapeutics: Current holder of stock options in a privately-held company; Forma Therapeutics: Consultancy; Novartis: Consultancy; Cellarity Inc.: Consultancy.

RetS inhibits Pseudomonas aeruginosa biofilm formation by disrupting the canonical histidine kinase dimerization interface of GacS

Bacterial signaling histidine kinases (HKs) have long been postulated to function exclusively through linear signal transduction chains. However, several HKs have recently been shown to form complex multikinase networks (MKNs). The most prominent MKN, involving the enzymes RetS and GacS, controls the switch between the motile and biofilm lifestyles in the pathogenic bacterium Pseudomonas aeruginosa. While GacS promotes biofilm formation, RetS counteracts GacS using three distinct mechanisms. Two are dephosphorylating mechanisms. The third, a direct binding between the RetS and GacS HK regions, blocks GacS autophosphorylation. Focusing on the third mechanism, we determined the crystal structure of a cocomplex between the HK region of RetS and the dimerization and histidine phosphotransfer (DHp) domain of GacS. This is the first reported structure of a complex between two distinct bacterial signaling HKs. In the complex, the canonical HK homodimerization interface is replaced by a strikingly similar heterodimeric interface between RetS and GacS. We further demonstrate that GacS autophosphorylates in trans, thus explaining why the formation of a RetS-GacS complex inhibits GacS autophosphorylation. Using mutational analysis in conjunction with bacterial two-hybrid and biofilm assays, we not only corroborate the biological role of the observed RetS-GacS interactions, but also identify a residue critical for the equilibrium between the RetS-GacS complex and the respective RetS and GacS homodimers. Collectively, our findings suggest that RetS and GacS form a domain-swapped hetero-oligomer during the planktonic growth phase of P. aeruginosa before unknown signals cause its dissociation and a relief of GacS inhibition to promote biofilm formation.

Comparing nonlinear optomechanical coupling in membrane-in-the-middle and single-cavity systems

In cavity optomechanics, nonlinear interactions between an optical field and a mechanical resonator mode enable a variety of unique effects in classical and quantum measurement and information processing. Here, we describe nonlinear optomechanical coupling in the membrane-in-the-middle (MIM) system in a way that allows direct comparison to the intrinsic optomechanical nonlinearity in a standard, single-cavity optomechanical system. We find that the enhancement of nonlinear optomechanical coupling in the MIM system as predicted by Ludwig et al (2012 Phys. Rev. Lett. 109 063601) is limited to the degree of sideband resolution of the system. Moreover, we show that the selectivity of the MIM system of nonlinear over linear transduction has the same limit as in a single cavity system. These findings put constraints on the experiments in which it is advantageous to use an MIM system. We discuss dynamical backaction effects in this system and find that these effects per cavity photon are exactly as strong as in a single cavity system, while allowing for reduction of the required input power. We propose using the nonlinear enhancement and reduced input power in realistic MIM systems towards parametric squeezing and heralding of phonon pairs, and evaluate the limits to the magnitude of both effects.

Experimental Analysis on the Transduction Coefficient of a Non-Linear Electromagnetic Energy Harvesting Device with Softening Stiffness

Nonlinear energy harvesting devices in the form of stiffness nonlinearity have emerged as among the effective solutions to overcome the performance limit of linear energy harvesting devices. However, up to now, researches on the nonlinear devices are only focusing on the ability to widen the bandwidth while the limit of employing linear transduction coefficient in a nonlinear system has yet to be heavily discussed. This paper investigates on the transduction coefficient for both linear and nonlinear systems of an electromagnetic energy harvesting device as a function of the excitation frequency. It is proven that the transduction coefficient of the nonlinear device is larger than its equivalent linear device, especially in the multi-stable solutions region. In common practice, the nonlinearity in the nonlinear system is considered weak, and its transduction coefficient is assumed to converge to the one produced by the linear system. The limits to which the transduction coefficient of a linear system can be employed on the nonlinear system were drawn based on the experimental analysis conducted on the proposed device. The device was designed to perform as a linear or nonlinear system, where the degree of nonlinearity was changed by varying the gap between the magnets. The limit of the transduction coefficient was determined from the analysis of the harmonic ratio. The results show that the linear transduction coefficient is valid to be employed to the nonlinear system when the harmonic ratio is less than five per cent at the multi-stable solutions region.

Linear Ubiquitin Code: Its Writer, Erasers, Decoders, Inhibitors, and Implications in Disorders.

The linear ubiquitin chain assembly complex (LUBAC) is a ubiquitin ligase composed of the Heme-oxidized IRP2 ubiquitin ligase-1L (HOIL-1L), HOIL-1L-interacting protein (HOIP), and Shank-associated RH domain interactor (SHARPIN) subunits. LUBAC specifically generates the N-terminal Met1-linked linear ubiquitin chain and regulates acquired and innate immune responses, such as the canonical nuclear factor-κB (NF-κB) and interferon antiviral pathways. Deubiquitinating enzymes, OTULIN and CYLD, physiologically bind to HOIP and control its function by hydrolyzing the linear ubiquitin chain. Moreover, proteins containing linear ubiquitin-specific binding domains, such as NF-κB-essential modulator (NEMO), optineurin, A20-binding inhibitors of NF-κB (ABINs), and A20, modulate the functions of LUBAC, and the dysregulation of the LUBAC-mediated linear ubiquitination pathway induces cancer and inflammatory, autoimmune, and neurodegenerative diseases. Therefore, inhibitors of LUBAC would be valuable to facilitate investigations of the molecular and cellular bases for LUBAC-mediated linear ubiquitination and signal transduction, and for potential therapeutic purposes. We identified and characterized α,β-unsaturated carbonyl-containing chemicals, named HOIPINs (HOIP inhibitors), as LUBAC inhibitors. We summarize recent advances in elucidations of the pathophysiological functions of LUBAC-mediated linear ubiquitination and identifications of its regulators, toward the development of LUBAC inhibitors.

No-oscillation theorem for the transient dynamics of the linear signal transduction pathway and beyond

Understanding the connection between the topology of a biochemical reaction network and its dynamical behavior is an important topic in systems biology. We proved a no-oscillation theorem for the transient dynamics of the linear signal transduction pathway, that is, there are no dynamical oscillations for each species if the considered system is a simple linear transduction chain equipped with an initial stimulation. In the nonlinear case, we showed that the no-oscillation property still holds for the starting and ending species, but oscillations generally exist in the dynamics of intermediate species. We also discussed different generalizations on the system setup. The established theorem will provide insights on the understanding of network motifs and the choice of mathematical models when dealing with biological data.

PAKT pathway activation is associated with PIK3CA mutations and good prognosis in luminal breast cancer in contrast to p-mTOR pathway activation

Numerous studies have focused on the PI3K/AKT/mTOR pathway in estrogen receptor positive (ER) breast cancer (BC), as a linear signal transduction pathway and reported its association with worse clinical outcomes. We developed gene signatures that reflect the level of expression of phosphorylated-Serine473-AKT (pAKT) and phosphorylated-Serine2448-mTOR (p-mTOR) separately, capturing their corresponding level of pathway activation. Our analysis revealed that the pAKT pathway activation was associated with luminal A BC while the p-mTOR pathway activation was more associated with luminal B BC (Kruskal–Wallis test p < 10−10). pAKT pathway activation was significantly associated with better outcomes (multivariable HR, 0.79; 95%CI, 0.74–0.85; p = 2.5 × 10−10) and PIK3CA mutations (p = 0.0001) whereas p-mTOR pathway activation showed worse outcomes (multivariable HR,1.1; 95%CI, 1.1–1.2; p = 9.9 × 10−4) and associated with p53 mutations (p = 0.04). in conclusion, our data show that pAKT and p-mTOR pathway activation have differing impact on prognosis and suggest that they are not linearly connected in luminal breast cancers.

Non‐covalent Functionalization of Multi‐wall Carbon Nanotubes with Polyarginine: Characterization and Analytical Applications for Uric Acid Quantification

AbstractWe report for the first time the non‐covalent functionalization of multiwall carbon nanotubes (MWCNTs) with polyarginine (Polyarg), the modification of glassy carbon electrodes (GCE) with the resulting Polyarg‐MWCNTs dispersion and the analytical application of Polyarg‐MWCNTs‐modified GCE for the quantification of uric acid. The optimum MWCNT‐Polyarg dispersion was obtained by sonicating for 5.0 min the mixture of 0.75 mg mL−1 MWCNTs and 0.50 mg mL−1 Polyarg. The dispersion was characterized by scanning electron microscopy, electrophoretic mobility, electrochemical impedance spectroscopy, cyclic voltammetry and amperometry. The presence of MWCNT‐Polyarg at GCE surface produced a drastic decrease in the overvoltages for the oxidation of hydrogen peroxide (300 mV) ascorbic acid (281 mV) and uric acid (70 mV) and for the reduction of hydrogen peroxide (200 mV), as well as an important decrease in the charge transfer resistances for hydrogen peroxide, hydroquinone/quinone and ferricyanide/ferrocyanide markers. The strong adsorption of uric acid at GCE/MWCNT‐Polyarg made possible the highly sensitive detection of this biomarker at nanomolar levels even in the presence of 1.0×10−4 M ascorbic acid by Adsorptive Stripping with medium exchange and linear scan voltammetry transduction. The quantification of uric acid in untreated human urine was very successful, demonstrating an excellent correlation (98 %) with the reference method used in clinical laboratories (Uricostat, Wiener Lab).

A Novel Wearable Apparatus to Measure Fingertip Forces in Manipulation Tasks Based on MEMS Barometric Sensors.

Artificial tactile sensing is a challenging research topic in robotics, motor control, and rehabilitation engineering encompassing multi-disciplinary skills and different technologies. This paper presents the development of a wearable tactile thimble system using MEMS barometric sensors and flexible printed circuit board. Barometric sensors were carefully processed to make them able to transduce contact forces. Thumb, index, and medium fingers were equipped with an array of six sensing elements each, covering the central, lateral, and medial aspects of the fingertip. The sensor integration, signal read-out and processing, hardware architecture of the device, along with the calibration protocol, were described. The test results showed adequate sensitivity at very low forces with an almost linear transduction range up to about 4N (RMSE: 0.04N). Tests on object manipulation tasks highlighted the value of the proposed system demonstrating the ability of measuring both the force amplitude and contact points, demonstrating the suitability of barometric sensors for tactile applications.

Voltage Amplifier Based on Organic Electrochemical Transistor

Organic electrochemical transistors (OECTs) are receiving a great deal of attention as amplifying transducers for electrophysiology. A key limitation of this type of transistors, however, lies in the fact that their output is a current, while most electrophysiology equipment requires a voltage input. A simple circuit is built and modeled that uses a drain resistor to produce a voltage output. It is shown that operating the OECT in the saturation regime provides increased sensitivity while maintaining a linear signal transduction. It is demonstrated that this circuit provides high quality recordings of the human heart using readily available electrophysiology equipment, paving the way for the use of OECTs in the clinic.

Systems pharmacology – Towards the modeling of network interactions

Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease. This requires consideration of several fundamental properties of biological systems behavior including: hysteresis, non-linearity, variability, interdependency, convergence, resilience, and multi-stationarity.Classical physiology-based PKPD models consider linear transduction pathways, connecting processes on the causal path between drug administration and effect, as the basis of drug action. Depending on the drug and its biological target, such models may contain expressions to characterize i) the disposition and the target site distribution kinetics of the drug under investigation, ii) the kinetics of target binding and activation and iii) the kinetics of transduction. When connected to physiology-based DS models, PKPD models can characterize the effect on disease progression in a mechanistic manner. These models have been found useful to characterize hysteresis and non-linearity, yet they fail to explain the effects of the other fundamental properties of biological systems behavior.Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders).In this contribution it is shown how physiology-based PKPD and disease models can be extended to account for internal systems interactions. It is demonstrated how SP models can be used to predict the effects of multi-target interactions and of homeostatic feedback on the pharmacological response. In addition it is shown how DS models may be used to distinguish symptomatic from disease modifying effects and to predict the long term effects on disease progression, from short term biomarker responses. It is concluded that incorporation of expressions to describe the interactions in biological network analysis opens new avenues to the understanding of the effects of drug treatment on the fundamental aspects of biological systems behavior.

The Elementary Operations of Human Vision Are Not Reducible to Template-Matching.

It is generally acknowledged that biological vision presents nonlinear characteristics, yet linear filtering accounts of visual processing are ubiquitous. The template-matching operation implemented by the linear-nonlinear cascade (linear filter followed by static nonlinearity) is the most widely adopted computational tool in systems neuroscience. This simple model achieves remarkable explanatory power while retaining analytical tractability, potentially extending its reach to a wide range of systems and levels in sensory processing. The extent of its applicability to human behaviour, however, remains unclear. Because sensory stimuli possess multiple attributes (e.g. position, orientation, size), the issue of applicability may be asked by considering each attribute one at a time in relation to a family of linear-nonlinear models, or by considering all attributes collectively in relation to a specified implementation of the linear-nonlinear cascade. We demonstrate that human visual processing can operate under conditions that are indistinguishable from linear-nonlinear transduction with respect to substantially different stimulus attributes of a uniquely specified target signal with associated behavioural task. However, no specific implementation of a linear-nonlinear cascade is able to account for the entire collection of results across attributes; a satisfactory account at this level requires the introduction of a small gain-control circuit, resulting in a model that no longer belongs to the linear-nonlinear family. Our results inform and constrain efforts at obtaining and interpreting comprehensive characterizations of the human sensory process by demonstrating its inescapably nonlinear nature, even under conditions that have been painstakingly fine-tuned to facilitate template-matching behaviour and to produce results that, at some level of inspection, do conform to linear filtering predictions. They also suggest that compliance with linear transduction may be the targeted outcome of carefully crafted nonlinear circuits, rather than default behaviour exhibited by basic components.

Ethylene Control of Fruit Ripening: Revisiting the Complex Network of Transcriptional Regulation.

The plant hormone ethylene plays a key role in climacteric fruit ripening. Studies on components of ethylene signaling have revealed a linear transduction pathway leading to the activation of ethylene response factors. However, the means by which ethylene selects the ripening-related genes and interacts with other signaling pathways to regulate the ripening process are still to be elucidated. Using tomato (Solanum lycopersicum) as a reference species, the present review aims to revisit the mechanisms by which ethylene regulates fruit ripening by taking advantage of new tools available to perform in silico studies at the genome-wide scale, leading to a global view on the expression pattern of ethylene biosynthesis and response genes throughout ripening. Overall, it provides new insights on the transcriptional network by which this hormone coordinates the ripening process and emphasizes the interplay between ethylene and ripening-associated developmental factors and the link between epigenetic regulation and ethylene during fruit ripening.

High-sensitivity linear piezoresistive transduction for nanomechanical beam resonators.

Highly sensitive conversion of motion into readable electrical signals is a crucial and challenging issue for nanomechanical resonators. Efficient transduction is particularly difficult to realize in devices of low dimensionality, such as beam resonators based on carbon nanotubes or silicon nanowires, where mechanical vibrations combine very high frequencies with miniscule amplitudes. Here we describe an enhanced piezoresistive transduction mechanism based on the asymmetry of the beam shape at rest. We show that this mechanism enables highly sensitive linear detection of the vibration of low-resistivity silicon beams without the need of exceptionally large piezoresistive coefficients. The general application of this effect is demonstrated by detecting multiple-order modes of silicon nanowire resonators made by either top-down or bottom-up fabrication methods. These results reveal a promising approach for practical applications of the simplest mechanical resonators, facilitating its manufacturability by very large-scale integration technologies.

Nonlinear optomechanics in the stationary regime

We have observed nonlinear transduction of the thermomechanical motion of a nanomechanical resonator when detected as laser transmission through a sideband unresolved (stationary) optomechanical cavity. Nonlinear detection mechanisms are of considerable interest as special cases allow for quantum nondemolition measurements of the mechanical resonator's energy. We investigate the origin of the nonlinearity in the optomechanical detection apparatus and derive a theoretical framework for the nonlinear signal transduction, and the optical spring effect, from both nonlinearities in the optical transfer function and second-order optomechanical coupling. By measuring the dependence of the linear and nonlinear signal transduction---as well as the mechanical frequency shift---on laser detuning from optical resonance, we provide estimates of the contributions from the linear and quadratic optomechanical couplings.

Ovarian cancer: interplay of vitamin D signaling and miRNA action.

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.

Positional specification in the segmental growth pattern of an early arthropod

In many arthropods, there is a change in relative segment size during post-embryonic development, but how segment differential growth is produced is little known. A new dataset of the highest quality specimens of the 429 Myr old trilobite Aulacopleura koninckii provides an unparalleled opportunity to investigate segment growth dynamics and its control in an early arthropod. Morphometric analysis across nine post-embryonic stages revealed a growth gradient in the trunk of A. koninckii. We contrastively tested different growth models referable to two distinct hypotheses of growth control for the developing trunk: (i) a segment-specific control, with individual segments having differential autonomous growth progression, and (ii) a regional control, with segment growth depending on their relative position along the main axis. We show that the trunk growth pattern of A. koninckii was consistent with a regional growth control producing a continuous growth gradient that was stable across all developmental stages investigated. The specific posterior-to-anterior decaying shape of the growth gradient suggests it deriving from the linear transduction of a graded signal, similar to those commonly provided by morphogens. A growth control depending on a form of positional specification, possibly realized through the linear interpretation of a graded signal, may represent the primitive condition for arthropod differential growth along the main body axis, from which the diverse and generally more complex forms of growth control in subsequent arthropods have evolved.

Release etching and characterization of MEMS capacitive pressure sensors integrated on a standard 8-metal 130 nm CMOS process

Monolithic post-processing and characterization of CMOS MEMS capacitive absolute pressure sensors co-integrated on an 8-metal BEOL (back-end-of-line) 130nm CMOS device is reported in this paper. An optimized foundry compatible etch process for an IBM CMOS fabricated top triple layered passivation is discussed. A mixture of wet and plasma dry etch process is proposed for both an elliptic and a rectangular structured pressure sensor capacitor. Lateral 125μm stiction free etch from opposite sides was performed successfully for the monolithically integrated diaphragms on the 130nm CMOS platform. Low power inductive coupled plasma using CHF3 gas along with high RF bias power is utilized to increase lateral etch rate compared to vertical etch rate. Mechanical and electrical characterization results indicate a successful etch of the triple layer passivation and the sacrificial oxide. Sensitivities of the fluorosilicate sealed absolute pressure sensors were measured to be 0.07mV/Pa and 0.05mV/Pa for the elliptic and rectangular element, respectively. In addition, the linear capacitive transduction dynamic range was found to be 0.32pF and 0.23pF, respectively, for the elliptic and rectangular element (for 80hPa pressure variation).