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Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo. Here, we describe the development of mature, expandable AT2 organoids derived from human fetal lungs which are phenotypically stable, can differentiate into AT1-like cells, and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health. Synopsis: Disorders of surfactant protein biology cause dysfunction of alveolar type 2 cells and can lead to interstitial lung disease. This study describes the development of genetically manipulable, mature human fetal-derived alveolar type 2 cell organoids that facilitate the in vitro investigation of human disease genes. Cryopreservable alveolar type 2 cell organoids, which can self-renew and differentiate to alveolar type 1 cells, can be derived from human fetal lungs. Fetal lung-derived alveolar type 2 (fdAT2) organoids traffic and secrete surfactant appropriately and have similar gene expression profiles to adult alveolar type 2 cells. Knock-down of the E3 ligase ITCH in fdAT2 organoids phenocopies a pathological surfactant protein C trafficking defect seen in a subset of individuals with familial pulmonary fibrosis. A forward genetic screen and the development of genetically manipulable fetal lung-derived alveolar type 2 cells identify the E3 ligase ITCH as a regulator of surfactant protein C trafficking. [ABSTRACT FROM AUTHOR]

Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation. Inducible genetic mosaics can provide information about cellular lineages that are otherwise difficult to obtain. Here the authors report a mosaic knockout system called Red2Flpe-SCON, which allows lineage tracing of wild-type and mutant cells using a multicolour fluorescent reporter in mice. [ABSTRACT FROM AUTHOR]

In this study, a noncontact fabric loop sensor based on magnetic-field-induced conductivity, which can simultaneously detect cardiac activity and respiration signals, was developed and the effects of the sensor's shape and measurement position on the sensing performance were analyzed. Fifteen male subjects in their twenties wore sleeveless shirts equipped with various types of fabric loop sensors (spiky, extrusion, and spiral), and the cardiac activity and respiratory signals were measured twice at positions P2, P4, and P6. The measurements were verified by comparing them against the reference electrocardiogram (ECG) and respiratory signals measured using BIOPAC® (MP150, ECG100B, RSP100C). The waveforms of the raw signal measured by the fabric loop sensor were filtered with a bandpass filter (1–20 Hz) and qualitatively compared with the ECG signal obtained from the Ag/AgCI electrode. Notwithstanding a slight difference in performance, the three fabric sensors could simultaneously detect cardiac activity and respiration signals at all measurement positions. In addition, it was verified through statistical analysis that the highest-quality signal was obtained at the measurement position of P4 or P6 using the spiral loop sensor. [ABSTRACT FROM AUTHOR]

Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular mechanisms governing these processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells, which subsequently lose their cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lung. This cell fate conversion is mediated via distinctive transitional cell states of damage‐associated transient progenitors (DATPs), recently shown to emerge during injury repair in mouse and human lungs. We further describe a YAP/TAZ signaling cascade to be integral for the fate conversion of secretory cells into AT1 fate, by modulating mTORC1/ATF4‐mediated amino acid metabolism in vivo. Importantly, we observed aberrant activation of the YAP/TAZ‐mTORC1‐ATF4 axis in the altered airway epithelium of bronchiolitis obliterans syndrome, including substantial emergence of DATPs and AT1 cells with severe pulmonary fibrosis. Genetic and pharmacologic inhibition of mTORC1 activity suppresses lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases. Synopsis: The molecular programs underlying injury‐induced plasticity in the lung epithelium remain unclear. Here, combined genetic and expression analysis uncovers YAP/TAZ as a driver of cell fate‐converting metabolic signaling in the airways, offering new potential targets for human lung diseases. Sustained YAP/TAZ activation in airway secretory cells induces differentiation into squamous alveolar type 1 (AT1) fate, perturbed tissue architecture, and fibrosis.Single‐cell profiling shows transient cell states of damage‐associated transient progenitors (DATPs) during secretory‐to‐AT1 cell transition.YAP/TAZ‐dependent uptake of essential amino acids via the Slc7a5/LAT1 is required for the acquisition of DATP‐AT1 cell fates.mTORC1 and ATF4 mediate YAP/TAZ‐dependent amino acid metabolism and cell fate conversion in ex vivo organoids and in vivo mouse lungs.Patients with pulmonary fibrosis show aberrant activation of YAP/TAZ and mTORC1‐ATF4 signaling in the airways. [ABSTRACT FROM AUTHOR]

Epithelial, stem‐cell derived organoids are ideal building blocks for tissue engineering, however, scalable and shape‐controlled bio‐assembly of epithelial organoids into larger and anatomical structures is yet to be achieved. Here, a robust organoid engineering approach, Multi‐Organoid Patterning and Fusion (MOrPF), is presented to assemble individual airway organoids of different sizes into upscaled, scaffold‐free airway tubes with predefined shapes. Multi‐Organoid Aggregates (MOAs) undergo accelerated fusion in a matrix‐depleted, free‐floating environment, possess a continuous lumen, and maintain prescribed shapes without an exogenous scaffold interface. MOAs in the floating culture exhibit a well‐defined three‐stage process of inter‐organoid surface integration, luminal material clearance, and lumina connection. The observed shape stability of patterned MOAs is confirmed by theoretical modelling based on organoid morphology and the physical forces involved in organoid fusion. Immunofluorescent characterization shows that fused MOA tubes possess an unstratified epithelium consisting mainly of tracheal basal stem cells. By generating large, shape‐controllable organ tubes, MOrPF enables upscaled organoid engineering towards integrated organoid devices and structurally complex organ tubes. [ABSTRACT FROM AUTHOR]

Despite recent research on joint motion measurement to monitor human body movement, current measurement techniques and tools have significant limitations, including requiring large space for measurement and causing discomfort in test subjects wearing motion sensors. Our study aims, first, to develop carbon nanotube (CNT)-based textile joint motion sensors. Second, ours study aims to identify the most suitable CNT-based sensor structure and attachment method for use on a wearable platform during general exercise speeds. Lastly, we used these sensors on the human body, using sleeves and legs to find the most stable location, and we used the CNT-based sensor condition to monitor joint motions. We utilized our CNT-based sensor, which has proper elasticity as well as conductivity, and applied it to the elbow and knee joints. Based on the strain gauge principle, we monitored the variance of electric resistance that occurred when the CNT-based sensor was stretched due to limb motion. Our study tested 48 types of sensors. These sensors were applied to the CNT using different base knit textiles as well as different attachment methods, layers, sensor lengths, and sensor widths. The four most successful sensor types, which showed superior efficacy over the others in joint motion measurement, were selected for further study. These four sensors were then used to measure the elbow and knee joint motions of human subjects by placing them on different locations on sleeves and legs. The CNT knit textile sensors best suited to measuring joint motions are those with a double-layered CNT knit and 5 cm long × 0.5 cm or 1 cm wide sensors attached to a polyester¬-based knit using a welding method. The best position for the sensor to more stably monitor joint motions was the "below hinge position" from the elbow or knee hinge joint. Our study suggests an alternative strategy for joint-motion measurement that could contribute to the development of more comfortable and human-friendly methods of human limb motion measurement. [ABSTRACT FROM AUTHOR]

The strain-gauge type textile sensors adopted in many studies on respiration-sensing wearable systems have been reported to have two major limitations that result in reduced sensing accuracy and insufficient durability of the sensor. The two limitations are the inability to accurately monitor the changes in the three-dimensional (3D) body contour during changes in the respiration cycle and the frequent occurrence of baseline drifts. To solve these issues, this study proposes new types of textile respiration rate sensors with a 3D structure, which measure the respiration rate based on the variation in the size of the contacting section's surface during respiration, rather than the changes in the length of the sensor, as in existing strain-gauge type sensors. Firstly, the sensing signals were analyzed based on morphology and size measurements. Then, the sensing reliability of three respiration rate sensor types, namely the no-filler, 3D hard, and 3D soft types, was analyzed by comparing their measurements with those of the SS5LB. Finally, the reproducibility and baseline drifts of the sensors' measurements were evaluated by taking and comparing repeated measurements. As a result, the consistency of the sensing signals of the SS5LB and those of the two types of 3D sensors was higher than those of the no-filler type sensor, and the 3D soft type sensor had the highest reliability and reproducibility among the three new types of sensors. The result showed relatively reduced baseline drifts in the two types of 3D sensors. [ABSTRACT FROM AUTHOR]

Textile-based triboelectric nanogenerators (TENGs) have received considerable attention for wearable applications owing to their significant advantages, such as flexibility, lightness, and breathability. Recently, several studies based on the modification of friction surfaces for improving the triboelectric output performance have been reported. However, previously reported methods require complicated fabrication processes and may deteriorate the intrinsic properties of a textile. Herein, we present a wearable TENG utilizing a textile composed of pile-embroidered (rough-textured) fibers as a contact surface. The deformability of the fibers originating from the suspended structure provides a large contact area that can participate in triboelectrification. This significantly increases charge density induced on the surface in response to a compressive force, resulting in a high output voltage of 113 V. The TENG also exhibits a high output power, which is 24 times higher than that of the TENG based on satin-embroidered (flat-textured) fibers. More importantly, owing to the conventional textile manufacturing process based on three-dimensional embroidery, the fabrication of our TENG is significantly simpler and more cost-effective than previously reported techniques. Experimental demonstrations as a wearable energy harvester highlight the utility of the TENG for generating electricity from various human motions. Based on ease of manufacturing and high output performance, the proposed harvester is a promising candidate as a low-cost power source for next-generation electronics, such as Internet of Things devices and self-powered smart clothing. [ABSTRACT FROM AUTHOR]

Direct investigation of the early cellular changes induced by metastatic cells within the surrounding tissue remains a challenge. Here we present a system in which metastatic cancer cells release a cell-penetrating fluorescent protein, which is taken up by neighbouring cells and enables spatial identification of the local metastatic cellular environment. Using this system, tissue cells with low representation in the metastatic niche can be identified and characterized within the bulk tissue. To highlight its potential, we applied this strategy to study the cellular environment of metastatic breast cancer cells in the lung. We report the presence of cancer-associated parenchymal cells, which exhibit stem-cell-like features, expression of lung progenitor markers, multi-lineage differentiation potential and self-renewal activity. In ex vivo assays, lung epithelial cells acquire a cancer-associated parenchymal-cell-like phenotype when co-cultured with cancer cells and support their growth. These results highlight the potential of this method as a platform for new discoveries. A cell-penetrating fluorescent marker is used to label cells in the metastatic tumour microenvironment, revealing a variety of cell types including parenchymal cells with lung stem-cell characteristics. [ABSTRACT FROM AUTHOR]

A reconfigurable spin logic device is realized using an asymmetric quantum well displaying strong Rashba spin splitting. This design is developed to remove the inefficient spin injection process and to utilize the Rashba-effect-induced electrochemical potential shifts. In this logic device, two ferromagnetic electrodes were deposited on two quantum well channels, respectively. The magnetization orientations of the ferromagnetic electrodes determine the function of the logic operation, and the polarity of the charge current is assigned to the logic input. The output voltage corresponds to the difference between potentials of the two ferromagnetic terminals, which read the electrochemical potentials of the individual quantum well channels. The detected signal induced by the Rashba channel is observed to be two orders of magnitude greater than the spin injection signal from the ferromagnetic source into the semiconductor channel. Four logic functions, i.e., the AND, OR, NAND, and NOR operations, are illustrated for a single device up to room temperature. [ABSTRACT FROM AUTHOR]

Bio-signal-sensing clothing has been actively developed worldwide. However, motion artifacts caused by a wearer’s motion degrade the bio-signal quality. A significant amount of work has been aimed at resolving this problem, but such work mainly focused on the application, rather than on the comfort, fashion, or function of the clothing. This study investigated the feasibility of reducing motion artifacts in the garment design by improving the garment function modules. To achieve this, the study comprised two parts: observation of the effect of the bodice module and that of the sleeve module. We found that the bodice module reduces motion artifacts and obtains stable signals of heart activity. Further, we found that the sleeve module reduces motion artifacts but not as significantly as the bodice module. These results suggest fundamental guidelines for applying apparel design techniques to heart-activity-sensing clothing based on the magnetic-induced sensing method. [ABSTRACT FROM AUTHOR]

In this research, we investigated the luminance efficiency of the computerized embroidery methods applied to flexible plastic optical fiber (POF) for realization of the textile display. Due to the nature of the flexible POF being similar to that of textile yarn, it has been possible to realize a flexible textile display by application of some adjusted fabrication methods. However, besides the simple property of flexibility, two requirements are still demanded for the flexible POF-based textile display: high luminance and the method for realization of pixels in a display. Among the fabrication methods, machine embroidery has feasibility to realize relatively higher luminance of flexible POF-based textiles through a simple procedure. The aim of this study is to evaluate of the feasibility of the embroidery method for the flexible POF-based textile display in terms of luminance, and an approach for a suitable condition in the embroidery method to realize the textile display. To do this, four embroidery methods, in which bending angles from around 90° to around 180° were applied to the flexible POF, were developed in this study. The measurement method was conducted identically on two types of POFs (flexible POFs and non-flexible POFs). The measurement points were selected in consideration of the distance from the light source and the rotation angle of the embroidery, depending on each embroidery design. Based on the resulting luminance efficiency according to the four embroidery methods, suitable conditions for the embroidery method to realize a relatively higher level of luminance for the textile display were suggested. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs. [Display omitted] • Delta NTD has enhanced S1/S2 cleavage in WT and Kappa, but not Omicron, through allostery • S1/S2 cleavage efficiency correlates with TMPRSS2 usage for entry in Calu3 cells • S1/S2 cleavage can be a proxy for prediction of efficiency in syncytium formation Meng et al. report that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions such as entry and cell-cell fusion in a spike context-dependent manner. These data may explain the lack of dominant SARS-CoV-2 inter-variant recombinants bearing breakpoints within spike. [ABSTRACT FROM AUTHOR]

The view that adult stem cells are lineage restricted has been challenged by numerous reports of bone marrow (BM)-derived cells giving rise to epithelial cells. Previously, we demonstrated that nonhematopoietic BM cells are the primary source of BM-derived lung epithelial cells. Here, we tested the hypothesis that very small embryonic like cells (VSELs) are responsible for this engraftment. We directly compared the level of BM-derived epithelial cells after transplantation of VSELs, hematopoietic stem/progenitor cells, or other nonhematopoietic cells. VSELs clearly had the highest rate of forming epithelial cells in the lung. By transplanting VSELs from donor mice expressing H2B-GFP under a type 2 pneumocyte-specific promoter, we demonstrate that this engraftment occurs by differentiation and not fusion. This is the first report of VSELs differentiating into an endodermal lineage in vivo, thereby potentially crossing germ layer lineages. Our data suggest that Oct4+ VSELs in the adult BM exhibit broad differentiation potential. S TEM C ells 2013;31:2759-2766 [ABSTRACT FROM AUTHOR]

Mechanisms that regulate regional epithelial cell diversity and pathologic remodeling in airways are poorly understood. We hypothesized that regional differences in cell composition and injury-related tissue remodeling result from the type and composition of local progenitors. We used surface markers and the spatial expression pattern of an SFTPC-GFP transgene to subset epithelial progenitors by airway region. Green fluorescent protein (GFP) expression ranged from undetectable to high in a proximal-to-distal gradient. GFPhi cells were subdivided by CD24 staining into alveolar (CD24neg) and conducting airway (CD24low) populations. This allowed for the segregation of three types of progenitors displaying distinct clonal behavior in vitro. GFPneg and GFPlow progenitors both yielded lumen containing colonies but displayed transcriptomes reflective of pseudostratified and distal conducting airways, respectively. CD24lowGFPhi progenitors were present in an overlapping distribution with GFPlow progenitors in distal airways, yet expressed lower levels of Sox2 and expanded in culture to yield undifferentiated self-renewing progeny. Colony-forming ability was reduced for each progenitor cell type after in vivo bleomycin exposure, but only CD24lowGFPhi progenitors showed robust expansion during tissue remodeling. These data reveal intrinsic differences in the properties of regional progenitors and suggest that their unique responses to tissue damage drive local tissue remodeling. S tem C ells 2012;30:1948-1960 [ABSTRACT FROM AUTHOR]

In article number 2003332 by Joo-Hyeon Lee, Yan Yan Shery Huang, and co-workers, a robust organoid engineering method is developed to "up-size" and "shape" organoids - miniature collections of cells which mimic biological features of an organ. The organoid fusion process is characterised by inter-organoid surface integration, luminal clearance, and lumina connection. The method, named Multi-Organoid Patterning and Fusion (MOrPF), is used to assemble scaffold-free macroscale airway tubes, leading to flowable organoid-on-a-chip, and branching tubular structures. [Extracted from the article]

In this study, a strain gauge sensor based on a change of contact or network structure between conductive materials was implemented using the handle-machine embroidery technique, and the variables (embroidery shape, embroidery distance, embroidery size, and implementation location) affecting its performance were studied. As a result of Experiment I on the structure of embroidery suitable for joint motion monitoring, the embroidery distance, rather than the embroidery size, was found to have a significant effect on the electric resistance changes caused by elongation. Based on the results of Experiment I, two types of zigzag embroideries, four types of embroideries with few contact points, and two types of embroideries with more contact points (all with short distances (2.0)) were selected for Experiment II (the dummy motion experiment). As a result of the dummy motion experiment, it was found that the locations of the suitable embroidered sensors for joint motion monitoring was the HJP (Hinge Joint Position) in the 'types without a contact point' (zigzag) and the LHJP (Lower Hinge Joint Position) in the 'types with more contact points'. On the other hand, although there was no consistency among the 'types with few contact points', the resistance changes measured by the 2CP and 7CP embroidered sensors showed similar figures and patterns, and the HJP location was most suitable. The resistance changes measured by the 4CP and 6CP embroidered sensors exhibited no consistent patterns, but the LHJP locations were more suitable. These results indicate that the location of the HJP is suitable for measuring joint motion in the 'type without a contact point', and the location of the LHJP is suitable for measuring joint motion when the number of contact points exceeds a certain limit. Among them, the average resistance change of the 9CP sensor located at the LHJP was 40 Ω with the smallest standard deviation of less than 1, and it is thus considered to have the best performance among all the sensors. [ABSTRACT FROM AUTHOR]

Simple Summary: The solved problem, the helical core sensor for spatial coordinate direction within the fiber was applied to monitor the microscopic repetitive pattern caused by the body structure on the body surface. The body motion state was measured using the strain change of the helical core in three-dimensional space For real-time monitoring, sophisticated sensing and stability against noise are required. The femtosecond laser processing allows us to check the measurement reliability of the sensor through the design of the long and short period gratings. This shows the possibility of monitoring spatial coordinates from one core to one core. It can be used as a wearable sensor. Sensitivity and reliability are essential factors for the practical implementation of a wearable sensor. This study explores the possibility of using a hybrid high-resolution Bragg grating sensor for achieving a fast response to dynamic, continuous motion and Bragg signal pattern monitoring measurement. The wavelength shift pattern for real-time monitoring in picometer units was derived by using femtosecond laser Bragg grating processing on an optical wave path with long-period grating. The possibility of measuring the demodulation system's Bragg signal pattern on the reflection spectrum of the femtosecond laser precision Bragg process and the long-period grating was confirmed. By demonstrating a practical method of wearing the sensor, the application of wearables was also explored. It is possible to present the applicability of sophisticated micro transformation measurement applications in picometer units. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of the shape and attachment position of stretchable textile piezoresistive sensors coated with single-walled carbon nanotubes on their performance in measuring the joint movements of children. The requirements for fabric motion sensors suitable for children are also identified. The child subjects were instructed to wear integrated clothing with sensors of different shapes (rectangular and boat-shaped), attachment positions (at the knee and elbow joints or 4 cm below the joints). The change in voltage caused by the elongation and contraction of the fabric sensors was measured for the flexion-extension motions of the arms and legs at 60°/s (three measurements of 10 repetitions each for the 60° and 90° angles, for a total of 60 repetitions). Their reliability was verified by analyzing the agreement between the fabric motion sensors and attached acceleration sensors. The experimental results showed that the fabric motion sensor that can measure children's arm and leg motions most effectively is the rectangular-shaped sensor attached 4 cm below the joint. In this study, we developed a textile piezoresistive sensor suitable for measuring the joint motion of children, and analyzed the shape and attachment position of the sensor on clothing suitable for motion sensing. We showed that it is possible to sense joint motions of the human body by using flexible fabric sensors integrated into clothing. [ABSTRACT FROM AUTHOR]

An Amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A-SOX2 transcriptional programme as a novel candidate for drug development. Amongst the non-small cell lung cancers, to date, lung squamous cell carcinoma remains the most challenging to treat. Here the authors report BCL11A as an important factor which together with SOX2 can drive lung squamous cell carcinoma development and highlight a potential novel therapeutic candidate for this devastating disease. [ABSTRACT FROM AUTHOR]