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Caenorhabditis elegans expresses human Werner syndrome protein (WRN) orthologs as two distinct proteins: MUT-7, with a 3′−5′ exonuclease domain, and CeWRN-1, with helicase domains. How these domains cooperate remains unclear. Here, we demonstrate the different contributions of MUT-7 and CeWRN-1 to 22G small interfering RNA (siRNA) synthesis and the plasticity of neuronal signaling. MUT-7 acts specifically in the cytoplasm to promote siRNA biogenesis and in the nucleus to associate with CeWRN-1. The import of siRNA by the nuclear Argonaute NRDE-3 promotes the loading of the heterochromatin-binding protein HP1 homolog HPL-2 onto specific loci. This heterochromatin complex represses the gene expression of the guanylyl cyclase ODR-1 to direct olfactory plasticity in C. elegans. Our findings suggest that the exonuclease and helicase domains of human WRN may act in concert to promote RNA-dependent loading into a heterochromatin complex, and the failure of this entire process reduces plasticity in postmitotic neurons.

Conventional seq2seq chatbot models only try to find the sentences with the highest probabilities conditioned on the input sequences, without considering the sentiment of the output sentences. Some research works trying to modify the sentiment of the output sequences were reported. In this paper, we propose five models to scale or adjust the sentiment of the chatbot response: persona-based model, reinforcement learning, plug and play model, sentiment transformation network and cycleGAN, all based on the conventional seq2seq model. We also develop two evaluation metrics to estimate if the responses are reasonable given the input. These metrics together with other two popularly used metrics were used to analyze the performance of the five proposed models on different aspects, and reinforcement learning and cycleGAN were shown to be very attractive. The evaluation metrics were also found to be well correlated with human evaluation.

The nematode Caenorhabditis elegans (C. elegans) has proven to be a powerful model organism for the study of many biological processes, with major implications for human health and disease. As progranulin is a pleiotropic, secreted protein with both cell autonomous and non-autonomous roles, a multicellular organism such as C. elegans is ideal for the investigation of its normal function and pathological effects. The C. elegans genome contains a progranulin-like gene known as pgrn-1. The nematode pgrn-1 encodes a protein with three cysteine-rich granulin domains, compared to the seven and a half granulins in the human protein. We have shown that C. elegans mutants lacking pgrn-1 appear grossly normal, but exhibit accelerated apoptotic cell engulfment as well as a stress resistance phenotype (Kao et al., Proc Natl Acad Sci U S A 108:4441-4446, 2011; Judy et al., PLoS Genet 9:e1003714, 2013). In addition, the roles of individual granulins can also be dissected in C. elegans (Salazar et al., J Neurosci 35:9315-9328, 2015). Here, we describe methods for studying apoptosis and stress response in C. elegans.

This study investigates the intercellular transport of yolk lipoproteins in Caenorhabditis elegans by using fluorescence lifetime imaging microscopy (FLIM) and fluorescent nanodiamonds (FNDs) as photostable labels and tracers. The yolk lipoproteins in the nematode are similar to human serum low-density lipoproteins (LDLs), serving as an intercellular transporter of fat molecules and cholesterol. To study this fundamentally important process, FNDs were first coated with yolk lipoprotein complexes (YLCs) and then microinjected into the intestinal cells of the living organism. Real-time imaging over a time period of more than 50 min with FLIM revealed the process of YLC-FND secretion from the intestine to the pseudocoelomic space, followed by transporting into oocytes and subsequent accumulation in the multi-cellular embryos derived from the oocytes. Colocalization studies of the rme-2 adult hermaphrodites expressing green fluorescent protein (GFP)-tagged YLCs confirmed that the injected YLC-FNDs were taken up by oocytes through endocytosis mediated by the LDL receptor, RME-2, functioning as an YLC receptor. Our results demonstrate that FND is useful as a biomolecular nanocarrier without significantly altering the functionality of the cargos for intercellular transport, cell-specific targeting, and long-term imaging applications in vivo.

This letter presents an optically transparent antenna, which is made of conductive AgHT coated film, with an improved efficiency by applying a highly conductive coating or metallization in the form of a very narrow strip to selective antenna areas of high current density. A measurement showed that the proposed method improved the maximum gain of a fabricated transparent antenna using the AgHT film from -5 dBi to 0 dBi at 2.2 GHz while preserving much of the optical transparency. A 3D electromagnetic model using a full-wave method of moments was developed to investigate the effect of width of the highly conductive narrow strip on the efficiency of the transparent antenna.

Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies.

This paper reports on the development of a broadband, low insertion loss, ohmic-contact MEMs switch for microwave and millimeter-wave applications. The switch is surface-micromachined and electrostatically-actuated with electromechanical performance simulated with analytical and numerical models that compare well to experiment. The switch has an actuation voltage of 30 V, a response time of 20 μs, and mechanical strength to withstand 109 actuations. A 3D electromagnetics scattering model developed iteratively with the electromechanical modeling predicts RF performance demonstrated to be greater than 50 dB of isolation below 2 GHz and less than 0.2 dB of insertion loss from DC through 40 GHz. ©1999 John Wiley & Sons, Inc. Int J RF and Microwave CAE 9: 348–361, 1999.

The 1/f noise of a series of Sb-heterostructure diodes with varying area has been measured. Standard power law formulas for the frequency and voltage dependence were found adequate to summarize the data. An inverse dependence of voltage noise spectral density on the area was determined, consistent with the simple resistor model. Simulations using the noise formula predict that pre-amplification gain in the 30 to 35 db range can produce a sub-1degK noise equivalent temperature difference in realistic imaging cameras

The negatively charged nitrogen-vacancy (NV–) center in bulk diamond is a photostable fluorophore with a radiative lifetime of 11.6 ns at room temperature. The lifetime substantially increases to ~20 ns for diamond nanoparticles (size ~ 100 nm) suspended in water due to the change in refractive index of the surrounding medium of the NV– centers. This fluorescence decay time is much longer than that (typically 1 − 4 ns) of endogenous and exogenous fluorophores commonly used in biological imaging, making it possible to detect NV–-containing nanodiamonds in vivo at the single particle level by fluorescence lifetime imaging microscopy (FLIM). We demonstrate the feasibility of this approach using Caenorhabditis elegans (C. elegans) as a model organism.

Summary Background Engulfment of apoptotic cells is important for cellular homeostasis and the development of multicellular organisms. Previous studies have shown that more than one engulfment receptors act upstream of the conserved signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO for cell corpse removal in C. elegans , but little is known about their identities, except for PSR-1. Results We show that in C. elegans , integrin functions as an engulfment receptor in the recognition and subsequent phagocytosis of apoptotic cells. Mutations in the integrin α gene ina-1 result in inefficient engulfment of apoptotic cells. The INA-1 extracellular domain binds to the surface of apoptotic cells in vivo. This binding requires the phospholipid scramblase SCRM-1, which promotes the exposure of phosphatidylserine, a key "eat me" signal in apoptotic cells. Furthermore, we identify an essential role of the nonreceptor tyrosine kinase SRC-1 in INA-1-mediated cell corpse removal. INA-1 and SRC-1 both act in the engulfing cells during the engulfment process and are colocalized in the phagocytic cups extending around apoptotic cells. Finally, our genetic and biochemical data suggest that SRC-1 relays the scrm-1 -dependent engulfment signal from INA-1 to the conserved motility-promoting signaling complex CED-2/CrkII-CED-5/Dock180-CED-12/ELMO for CED-10/Rac activation, probably by interactions with CED-2 and the INA-1 cytoplasmic domain, leading to the internalization of apoptotic cells. Conclusions Our findings provide evidence that integrin functions as an engulfment receptor at the whole-organism level and reveal a nonconventional signaling pathway in which SRC provides a FAK-independent linkage between integrin α and the common motility-promoting signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO to promote the internalization of apoptotic cells.

A real-time near IR-to-visible image converter using a Hughes silicon liquid-crystal light valve (Si LCLV) has been demonstrated. A 1.06-microm image was converted to a 0.633-microm laser wavelength. The major advantages of this near-IR-to-visible image converter are its high sensitivity, broad bandwidth, coherent- (incoherent-) to-coherent (incoherent) image conversion, up and down wavelength conversion capability, high resolution (10(5) resolution elements), room-temperature operation, and high damage threshold.

Technology for passive millimeter wave imaging has been maturing over the last 4-5 years. One key piece of technology that will allow for large scale production is a low cost front-end receiver. We have developed a two chip solution that addresses this need at W-band. A four stage InP LNA with a pre-matched Sb-heterostructure diode provides a low noise equivalent temperature difference (NETD). Our fabricated chipset provides sensitivities of 10,000 mV/muW over a 22 GHz noise equivalent bandwidth and an NETD of 0.8 K. To our knowledge, this is the best performance to date of a two chip solution for a passive millimeter wave radiometer.

Sb-heterostructure diodes have become the detector of choice for W-band millimeter wave imaging cameras now being commercialized or in prototype development. Here we optimize the diode impedance to yield a minimum noise equivalent power (NEP). The goal is to decrease the gain required of the front-end LNA. Measured W-band sensitivities for two diodes are 3500 and 5500V/W. Their zero bias differential resistance values imply Johnson noise limited NEP's of 0.98 and 0.83pW/Hz1/2, respectively, much less than obtained from conventional biased Schottky diodes. A MMIC version of the diode detector has been simulated with an integrated bandwidth of ~ 30 GHz at W-band. The simulated temperature sensitivity (NEΔT) with an HRL W-band LNA on the front end is

We report on the development of a new MEMS-based quartz resonator technology that allows for the processing and integration of VHF to UHF high-Q oscillators and filters with high-speed silicon or III-V electronics. This paper describes the first demonstration of prototype oscillators and filters using this newly developed technology. We present impedance, Q, and temperature sensitivity data of UHF resonators along with phase noise and Allan deviation measurements. Our first 2-pole filter data showing low insertion loss is also presented. Finally, the results of power handling measurements are described for applications where high levels of background signals are present.

The figure of merit for RF detectors, noise-equivalent power (NEP), is determined by the noise divided by the sensitivity. Thus, the challenge is to design a diode structure that has low junction resistance while maintaining a large nonlinearity. This work presents sensitivity and noise measurements for Sb-heterostructure backward diodes with varying barrier thicknesses and cross-sectional areas. Nominal diode areas are 2x2mm2 and 3x4mm2 with 15Å and 20Å barriers. The best NEP measured to date is 1.19 pW/rtHz at 36.5 GHz.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We report on the development of a new MEMS quartz resonator technology that allows for the processing and integration of VHF to UHF high-Q oscillators and filters with high-speed silicon or III-V electronics. The paper describes the successful demonstration of new wafer bonding and dry plasma etching processes that make quartz-MEMS technology possible. We present impedance, Q, and temperature sensitivity data along with comparison to 3D harmonic and thermal analysis of VHF-UHF resonators. We also show Coventor simulation data of our first two- and three-pole monolithic crystal filter designs as well as a filter array layout which facilitates integration with front-end RF electronics and switches. Finally, we demonstrate a mechanical tuning technique for our resonators utilizing focused-ion-beam (FIB) technology.

We report on the development of a new microelectronic mechanical system (MEMS)-based quartz resonator technology that allows for the processing and integration of VHF to UHF high-Q oscillators and filters with high-speed silicon or III-V electronics. This paper describes the first demonstration of prototype oscillators and filters using this newly developed technology. We present impedance, Q, and temperature sensitivity data of UHF resonators along with phase noise and Allan deviation measurements. Our first 2-pole filter data showing low insertion loss are also presented. Finally, the results of power handling measurements are described for applications where high levels of background signals are present. © 2005 IEEE.

Metal contact RF MEMS switch circuit elements have been developed to be used as building blocks for wideband signal routing. A switch element can have up to four switches fabricated monolithically on a single GaAs chip. More complicated switch circuits can be constructed by assembling multiple basic switch elements on a hybrid RF interconnection printed circuit board. In this paper, two basic types of switch functions are presented, single-pole multiple-throw switch elements and matrix switch elements. Measured insertion loss and isolation performances of these circuits are presented.

RF MEMS switches with metal-metal contacts are being developed for microwave applications where broadband, high linearity performance is required. These switches provide less than 0.2 dB insertion loss through 40 GHz. This paper describes the integration of these switches into selected microwave components such as reconfigurable antenna elements, tunable filters, switched delay lines, and SPDT switches. Microwave and millimeter wave measured results from these circuits are presented.

Clearance of apoptotic cells by engulfment plays an important role in the homeostasis and development of multicellular organisms. Despite the fact that the recognition of apoptotic cells by engulfment receptors is critical in inducing the engulfment process, the molecular mechanisms are still poorly understood. Here, we characterize a novel cell corpse engulfment pathway mediated by the integrin α subunit PAT-2 in Caenorhabditis elegans and show that it specifically functions in muscle-mediated engulfment during embryogenesis. Inactivation of pat-2 results in a defect in apoptotic cell internalization. The PAT-2 extracellular region binds to the surface of apoptotic cells in vivo, and the intracellular region may mediate signaling for engulfment. We identify essential roles of small GTPase CDC-42 and its activator UIG-1, a guanine-nucleotide exchange factor, in PAT-2–mediated cell corpse removal. PAT-2 and CDC-42 both function in muscle cells for apoptotic cell removal and are co-localized in growing muscle pseudopods around apoptotic cells. Our data suggest that PAT-2 functions through UIG-1 for CDC-42 activation, which in turn leads to cytoskeletal rearrangement and apoptotic cell internalization by muscle cells. Moreover, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, which signal through the conserved signaling molecules CED-5 (DOCK180)/CED-12 (ELMO) or CED-6 (GULP) respectively, preferentially act in epithelial cells to mediate cell corpse removal during mid-embryogenesis. Our results show that different engulfing cells utilize distinct repertoires of receptors for engulfment at the whole organism level., Author Summary When cells undergo apoptosis, their corpses are quickly recognized and phagocytosed by engulfing cells. Although many cell types, such as muscle cells and epithelial cells, possess the ability to remove apoptotic cells, little is known about the receptors and signaling pathways used for apoptotic cell uptake by these “amateur” phagocytes. We show that, in Caenorhabditis elegans, integrin PAT-2/PAT-3 functions as an engulfment receptor in muscle cells. The integrin α subunit PAT-2 mediates both the recognition and subsequent phagocytosis of apoptotic cells. PAT-2 signals through UIG-1 for CDC-42 activation, leading to the cytoskeletal reorganization as the engulfing muscle cell extends pseudopods around the apoptotic cell. Furthermore, in contrast to PAT-2, the other integrin α subunit INA-1 and the engulfment receptor CED-1, both of which appear to act upstream of small GTPase CED-10 (RAC1), predominantly function in epithelial cells to mediate cell corpse removal. Therefore, epithelial cells and muscle cells employ different engulfment receptors for apoptotic cell recognition, downstream signaling, and specific GTPase activation during apoptotic cell removal.

This paper covers recent theoretical and experimental work in the area of multiple quantum well modulators with particular emphasis on optical processing applications. The paper covers the analysis of MQW as a modulator element as well as one- and two-dimensional spatial light modulator structures, both optically and electrically addressed. Recent experimental efforts in developing MQW modulators structures are surveyed. Finally, future development such as quantum dots as well as the relative role of MQW within the family of spatial light modulators is discussed.

The use of nanomechanical resonators for chemical and bioagent detection has attracted a large amount of interest in recent years, since the mass noise floor scales directly with the mass of the resonator for a given frequency stability. In order for this technology to be applied to hand-held units, the resonators should ideally be integrated with the oscillator and counter electronics, have high-Q and high frequency stability in air, and have low-temperature sensitivity. We present a quartz-based ultrahigh-frequency resonator/oscillator technology that addresses these important issues. Miniaturized shear-mode resonators with frequencies approaching 3GHz and f×Q products of >1.0×1013Hz have been fabricated on Si using low-temperature wafer bonding and deep reactive ion quartz etching. Allan deviation levels of 1.0×10−8 for 100s integration times have been measured for a 326MHz Pierce oscillator design. In addition, the temperature stability matches that expected for AT-cut crystal resonators. We present p...

A MEMS switch has been developed for microwave applications. The switch has an actuation of 30 V, a response time of 20 /spl mu/s, and mechanical robustness to withstand 10/sup 9/ actuations. An RF performance with >50 dB isolation below 2 GHz and

The passive quadrature demodulator (PQD) eliminates the phase stretcher and feedback electronics frequently used in fiber interferometric sensors by passively extracting the desired signal using two distinct interferometers which differ in phase by \pi/2 . A fusion technique is described to fabricate a fiber PQD which is sufficiently stable with respect to temperature, polarization, and wavelength to maintain the sensitivity of interferometric sensors constant to 0.25 dB.

The interband optical absorption of a nonuniform semiconductor quantum dot system is calculated. The effect of dot size variation on the resolvability of the absorption peaks is estimated. The dots are assumed to be cubic, with a size distribution described by a Gaussian function. It is shown that the total absorption spectrum of such a dot system depends strongly on the dot size distribution described by the parameter ξ, the ratio of the standard deviation of the dot size to the average dot size of the system. The range of ξ values for which the absorption peaks are resolvable is given.

In this paper recent theoretical and experimental work in the area of multiple quantum well (MQW) modulators for optical processing applications is presented. The theoretical work includes the application of the effective mass approximation to compositional MQW structures and the use of a two-band tight-binding approximation to doping-modulated nipi structures. The theoretical calculations are used to obtain electric-field-dependent absorption and refractive index in the above MQW structures. The experimental results of a 4µm thick GaAs/GaAIAs MQW modulator show an ~ 10:1 on/off ratio with an applied voltage of ~ 20 V (absorption change ~ 6000 cm-1 at E ~ 50 kV/cm) and ~0.4 rad of phase shift with an applied voltage of 10 V (~0.04 at E ~25 kV/cm). Such high electro-optical modulations have previously been reported only in the MQW optical waveguide modulator. Concepts of photoactivated, electrically addressed MQW spatial light modulators and IR-to-visible MQW spatial light modulators are presented. Finally, theoretical evaluation of quantum dot arrays and their potential use in spatial light modulators are discussed.

Results of thermal switching of the electrical and optical properties of thin films of Ag2S are presented. The procedures for the preparation of the thin film are described. Film characteristics including crystal structure, composition for various thicknesses, and spectral transmittance/reflectance versus electrical conductivity are given. In addition, we have demonstrated electrical control (not due to Joule heating) of the spectral transmittance over the Far-IR to millimeter wavelength region. The application of the latter effect to infrared-millimeter devices such as modulators, variable attenuators, switchable polarizers, and tunable filters is stressed.© (1981) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In this paper recent theoretical and experimental work in the area of multiple quantum well modulators is presented. The theoretical work includes the application of the effective mass approximation to compositional MQW structures and the use of a two-band tight-binding approximation to doping modulated Nipi structures. The theoretical calculations are used to obtain electric-field-dependent absorption and refractive index in the above MQW structures. Experimental electroabsorption in compositional MQW structures is described, as well as preliminary optical characterization of Nipi structures. Concepts of photoactivated and electrically addressed MQW-spatial light modulators are presented. Finally, theoretical evaluation of quantum dot arrays and their potential use in spatial light modulators is discussed.