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Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9–5p, miR-9–5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9–5p, miR-9–5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9–5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9–5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9–5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

Abstract Chronic pain is highly prevalent and is linked to a broad range of comorbidities, including sleep disorders. Epidemiological and clinical evidence suggests that chronic sleep disruption (CSD) leads to heightened pain sensitivity, referred to as CSD-induced hyperalgesia. However, the underlying mechanisms are unclear. The thalamic reticular nucleus (TRN) has unique integrative functions in sensory processing, attention/arousal and sleep spindle generation. We report that the TRN played an important role in CSD-induced hyperalgesia in mice, through its projections to the ventroposterior region of the thalamus. Metabolomics revealed that the level of N-arachidonoyl dopamine (NADA), an endocannabinoid, was decreased in the TRN after CSD. Using a recently developed CB1 receptor (cannabinoid receptor 1) activity sensor with spatiotemporal resolution, CB1 receptor activity in the TRN was found to be decreased after CSD. Moreover, CSD-induced hyperalgesia was attenuated by local NADA administration to the TRN. Taken together, these results suggest that TRN NADA signaling is critical for CSD-induced hyperalgesia.

Pore characteristics of concrete material have a significant impact on its thermal conductivity, however, very little pays attention to the impact of pore characteristics on thermal conductivity of light-weight aggregate concrete including microencapsulated phase change materials (MPCM-LWAC). In this paper, the experimental investigation was carried out to reveal the thermal conductivity and pore characteristics of LWAC including different MPCM dosage. The quantitative analysis on pore characteristic parameters (Porosity, Flatness, Spherical degree) that were extracted based on stereology theory has proved a clear relationship of pore characteristics in regard to MPCM dosage. On the basis of experimental investigation, the theoretical investigation was performed to establish the theoretical model suitable for the effective thermal conductivity (ETC) of MPCM-LWAC. To consider the impact of pore characteristics on ETC of MPCM-LWAC, two-step method was proposed to improve the common theoretical model. Results shown that the addition of MPCM caused the increasing of porosity of MPCM-LWAC, while little impact on the Flatness and Spherical degree. Regardless of the MPCM dosage embedded into LWAC, the data sets of Flatness and Spherical degree follow the Lognormal Distribution and Normal distribution respectively. The position parameter of Normal distribution was determined as the shape factor in improved H–C model by using retrograde method. The ETC of MPCM-LWAC getting from the improved H–C model were in better agreement with the experimental results. Hence, the improved H–C model was recommended as the theoretical model to predict the ETC of MPCM-LWAC.

Background: In vivo two-photon imaging is a reliable method with high spatial resolution that allows observation of individual neuron and dendritic activity longitudinally. Neurons in local brain regions can be influenced by global brain states such as levels of arousal and attention that change over relatively short time scales, such as minutes. As such, the scientific rigor of investigating regional neuronal activities could be enhanced by considering the global brain state. New method: In order to assess the global brain state during in vivo two-photon imaging, CBRAIN (collective brain research platform aided by illuminating neural activity), a wireless EEG collecting and labeling device, was controlled by the same computer of two-photon microscope. In an experiment to explore neuronal responses to isoflurane anesthesia through two-photon imaging, we investigated whether the response of individual cells correlated with concurrent EEG changes induced by anesthesia. Results: In two-photon imaging, calcium activities of the excitatory neurons in the primary somatosensory cortex disappeared in about 30s after to the initiation of isoflurane anesthesia. The simultaneously recorded EEG showed various transitional activity for about 7 min from the initiation of anesthesia and continued with burst and suppression alternating pattern thereafter. As such, there was a dissociation between excitatory neuron activity of the primary somatosensory cortex and the global brain activity under anesthesia. Comparison with existing method(s): Existing methods to combine two-photon and EEG recording used wired EEG recording. In this study, wireless EEG was used in conjunction with two-photon imaging, facilitated by CBRAIN. More importantly, built-in algorithms of the CBRAIN can automatically detect brain state such as sleep. The codes used for EEG classification are easy to use, with no prior experience required. Conclusion: Simultaneous recording of wireless EEG and two-photon imaging provides a practical way to capture individual neuronal activities with respect to global brain state in an experimental set-up.

Abstract TNF receptor-associated factors (TRAFs) are signaling adaptor proteins that play a crucial role in regulating cellular receptors’ signaling transduction to downstream pathways and exert multifaceted roles in regulating signaling pathways, cell survival, and carcinogenesis. The 13-cis-retinoic acid (RA), an active metabolite of vitamin A, exhibits anti-cancer properties, but the development of retinoic acid resistance poses a challenge in clinical application. This study aimed to investigate the relationship between TRAFs and retinoic acid sensitivity in various cancers. Here, we revealed that TRAFs’ expression varied significantly across The Cancer Genome Atlas (TCGA) cancer cohorts and human cancer cell lines. Additionally, inhibiting TRAF4, TRAF5, or TRAF6 improved retinoic acid sensitivity and reduced colony formation in ovarian cancer and melanoma cells. Mechanistically, knocking down TRAF4, TRAF5, or TRAF6 in retinoic acid-treated cancer cell lines increased the levels of procaspase 9 and induced cell apoptosis. Further in vivo studies using the SK-OV-3 and MeWo xenograft models confirmed the anti-tumor effects of TRAF knockdown combined with retinoic acid treatment. These findings support that combination therapy with retinoic acid and TRAF silencing may offer significant therapeutic advantages in treating melanoma and ovarian cancers.

Trigeminal neuralgia (TN) is a classic neuralgic pain condition with distinct clinical characteristics. Modeling TN in rodents is challenging. Recently, we found that a foramen in the rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root. Using this access, we developed a foramen lacerum impingement of trigeminal nerve root (FLIT) model and observed distinct pain-like behaviors in rodents, including paroxysmal asymmetric facial grimaces, head tilt when eating, avoidance of solid chow, and lack of wood chewing. The FLIT model recapitulated key clinical features of TN, including lancinating pain–like behavior and dental pain–like behavior. Importantly, when compared with a trigeminal neuropathic pain model (infraorbital nerve chronic constriction injury [IoN-CCI]), the FLIT model was associated with significantly higher numbers of c-Fos–positive cells in the primary somatosensory cortex (S1), unraveling robust cortical activation in the FLIT model. On intravital 2-photon calcium imaging, synchronized S1 neural dynamics were present in the FLIT but not the IoN-CCI model, revealing differential implication of cortical activation in different pain models. Taken together, our results indicate that FLIT is a clinically relevant rodent model of TN that could facilitate pain research and therapeutics development.

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a “normal” operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain–like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos–expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a “normal” range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.

The shape of instantaneous water surface profiles for the unsteady flow in the tunnel model can be determined by measuring the instantaneous water levels at multiple points synchronously. However, the measurement accuracy of the ultrasonic method is affected greatly because of the complex state of the water surface when water level changes rapidly. Using an optical method, multicamera synchronous measurement is difficult to control, and the cost is high. For single camera measurement, the reading of the steel ruler in the image cannot be clearly seen when the distance between the measuring point and single camera is far. When the distance is short, all steel rulers cannot be captured at the same time. Hence, in this paper, a single camera and fixed scale compensation method for instantaneous water level observation in unsteady flow is proposed. A series of fixed scales is placed with the same height and width near the water surface to be measured. In order to capture dynamic images of all fixed scales with a clear water surface, a single camera is set at a far position to continuously record the water level change process within the model range. According to the height of the fixed scale, the image accuracy is compensated and the effect of the wide-angle image distortion is automatically avoided. The water level elevation is obtained according to the relationship between the fixed scale and the water surface. In this paper, the unsteady flow model measuring test is applied to the Southern Main Tunnel and the Water Distribution Pool of the Huangchigou Water Diversion Project. The accuracy of this method in measuring the dynamic water level is 1–2 mm, which meets the accuracy requirement and greatly reduces the observation cost of the model test. The proposed method may also be suitable for measuring the instantaneous water level of the unsteady flow in other similar hydraulic model tests.

The Huangchigou Water Distribution Hub is the core water distribution structure in the Hanjiang-to-Weihe Valley Water Diversion Project. It plays a decisive role in ensuring the safety of downstream water transport, allocating water reasonably and reducing the waste of abandoned water. The study on its unsteady-flow hydraulic characteristics is of key significance in the formulation for the opening and closing rules of the hub gates. The shape of the instantaneous water surface profile is an important factor for the hydraulic characteristics of the unsteady flow in the hub. The effect of the traditional instantaneous water level measurement method is not ideal. A single-camera and fixed-scale compensation method is proposed for an instantaneous water level observation. The proposed method meets the requirement of measurement accuracy and reduces the observation cost of the model test. The unsteady-flow test of the hydraulic model in the Southern Main Tunnel of the Huangchigou Water Distribution Hub was carried out under two operating conditions when the model flow is 0.0246 m3/s. Precise data such as wave front propagation velocity and hydraulic oscillation recovery time of unsteady flows in the Southern Main Tunnel was obtained. It has an important reference value for the research and design of water transfer dispatching and gate-opening and gate-closing rules for the Huangchigou Water Distribution Hub.

Optimizing supplemental irrigation (SI) measures and enhancing stem lodging resistance can be the keys to achieving a high and stable yield and high efficiency in wheat. The experiment was established as a two-factor field trial in 2018–2020. We used four SI combinations at different stages: rain-fed (T0), SI at jointing (T1), SI at jointing + anthesis (T2), and SI at regreening + jointing + anthesis (T3) with ‘Bainong4199’ (BN4199) and ‘Zhoumai18’ (ZM18) as experimental materials. We researched the effects of different SI combinations on the stem characteristics, stem vigor, grain filling, and yield of winter wheat. The results suggest that the basal internode at the anthesis stage grew with the increase in SI amount, but the stem fracture resistance of T1 and T2 was higher than that of T0 and T3. As grain filling continued, the lodging index increased and stem vigor decreased. In comparison with T3, the average stem lodging index of T2 decreased by 21.92% for ‘BN4199’ and 36.63% for ‘ZM18’, but the WUE increased by 29.76% and 14.92%, respectively. The grain yield increased with the increase in irrigation times during the growth period; there was no significant difference between T2 and T3 in 2018–2019. In a biennial comparison, the grain yield of all treatments in 2019–2020 was significantly lower than those in 2018–2019, and the grain yield of ‘ZM 18’ was lower than that of ‘BN 4199’. Correlation analysis displayed that there were significant positive correlations between post-anthesis stem vigor and the dry matter contribution rate of post-anthesis to grains and between the grain filling rate at 21–28 days after anthesis (DAA) and stem strength at 30 DAA. In summary, selecting a high-yield lodging-resistant wheat variety with SI at jointing and anthesis was beneficial for forming strong stems and maintaining higher stem vigor at the later growth stage for grain filling, which reduced lodging risk and ensured high yield and high WUE.

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut–brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut–brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.

The addition of microencapsulated phase-change materials (MPCM) to concrete will inevitably cause changes in the mechanical and thermal properties of concrete, and this is vitally important for the safety and energy saving of concrete building components. In this research, shale ceramsite and shale ceramics sand were used as the main raw materials to produce lightweight aggregate concrete (LWAC) mixed with MPCM. In order to investigate the effect of MPCM content and phase-change cycle numbers on the mechanical and thermal properties of MPCM-LWAC, two groups of MPCM-LWAC specimens were prepared. One group consists of specimens containing 2.5%, 5.0%, 7.5%, and 10% MPCM, respectively, and they are used to reveal the change law of tensile strength, compressive strength, enthalpy, and specific heat capacity of LWAC integrated into MPCM. The other group includes specimens with the same MPCM content, but the specimens are subjected to different phase-change cycle numbers of 50, 100, 150, and 200 at the environment temperature of −10–60°C to study the thermal properties of MPCM-LWAC. Findings from the experimental results include the following: (1)The tensile and compressive strengths of MPCM-LWAC concrete are negatively correlated with the MPCM content, while the enthalpy and specific heat capacity are positively correlated with the MPCM content. When the MPCM content reaches 10%, the compressive and tensile strengths of MPCM-LWAC decreased, respectively, by 45.49% and 52.63% than the LWAC without MPCM. (2) Under heating and curing condition, the corresponding maximum specific heat capacity of LWAC with 10% MPCM is 328.35% and 249.50% higher than the LWAC without MPCM, respectively, and the average specific heat capacities increase 71.21% and 44.94%, respectively. (3) The melting enthalpy of MPCM-LWAC is slightly larger than the curing enthalpy, and the difference is more noticeable with the increase of MPCM content. In addition, when the number of phase-change cycle is below 200, the compressive strength and splitting tensile strength of MPCM-LWAC decrease by less than 5%, and the specific heat capacity decreases by less than 1.33%. Hence, it concludes that shale ceramsite concrete with MPCM has promising application prospects.

The study on microscopic mechanical properties of mineral is of great significance to reveal the damage mechanism of rock and can provide important basis for nondestructive testing of building materials and assisted rock breaking technology. As the main test method for rock and mineral microscopic mechanical properties, nanoindentation test has several parameters such as loading time, indentation depth, and loading rate, which have great influence on the test results. Three schemes are designed as follows: (1) The loading and unloading rates remain unchanged, and the holding time is 0 s, 5 s, 10 s, 20 s, 50 s, and 100 s, respectively. (2) Ten cycles of loading and unloading tests are used to calculate micromechanical indexes at different indentation depth. (3) The maximum load and holding time remain unchanged, and the loading rate is 5 mN/s, 10 mN/s, 20 mN/s, 30 mN/s, 40 mN/s, and 50 mN/s, respectively. The results show that (1) with the increase of holding time, the elastic modulus and hardness of feldspar decrease sharply between 0 s and 5 s, decrease slightly between 5 s and 10 s, and stabilize after 10 s. The creep displacement of feldspar is positively correlated with holding time. The holding time does not change the development path of creep displacement. (2) With the increase of indentation depth, the elastic modulus and hardness of feldspar decrease gradually and become stable when the indentation depth is more than 350 nm. (3) The elastic modulus and hardness of quartz increase with loading rate. The maximum indentation depth and residual indentation depth decrease with the increase of loading rate. The creep displacement increases with loading rate, while the creep compliance decreases with the increase of loading rate. With the increase of holding time, the creep rate decreases and tends to be stable. The results provide theoretical basis for obtaining more accurate rock nanoindentation mechanical properties and revealing rock damage mechanism.

Wind speed is the most essential factor causing wheat lodging. Accurate understanding of the wind speed characteristics at near-surface layer of wheat fields and its effect on lodging is the basis of objective evaluation of wheat lodging resistance. In this paper, the characteristics of wind speed at the near-surface layer of wheat fields and their impact on lodging were studied. A new device was proposed for directly measuring the critical thrust force of wheat population lodging resistance in the field based on the black box method. A novel wheat stem lodging resistance evaluation method/model was established based on the critical thrust force of wheat population stem lodging and the wind speed characteristics of field near-surface layer. The method used the lodging critical wind speed as the index of wheat lodging resistance, which was verified by wind tunnel and field experiment. The results showed that there was a significant positive correlation between the critical wind speed of wheat lodging resistance and its critical thrust force. The values of wheat canopy apparent roughness length, wind attack angle, ventilation coefficient and other wind field characteristics had important effects on the calculation of wheat lodging resistance critical wind speed. The method can eliminate bias when calculating wheat lodging resistance by considering only one or a few indicators and the results of field lodging evaluation were consistent with those of field lodging survey. The method is simple and can be used to assess the lodging resistance of wheat, select extension regions for wheat varieties, and evaluate lodging factors in the field.

To achieve a better understanding of Holocene climate change in the monsoon regions of China, we investigated the molecular distributions and carbon and hydrogen isotope compositions (δ13C and δD values) of long-chain n-alkanes in a peat core from the Shiwangutian (SWGT) peatland, south China over the last 9 ka. By comparisons with other climate records, we found that the δ13C values of the long-chain n-alkanes can be a proxy for humidity, while the δD values of the long-chain n-alkanes primarily recorded the moisture source δD signal during 9-1.8 ka BP and responded to the dry climate during 1.8-0.3 ka BP. Together with the average chain length (ACL) and the carbon preference index (CPI) data, the climate evolution over last 9 ka in the SWGT peatland can be divided into three stages. During the first stage (9-5 ka BP), the δ13C values were depleted and CPI and Paq values were low, while ACL values were high. They reveal a period of warm and wet climate, which is regarded as the Holocene optimum. The second stage (5-1.8 ka BP) witnessed a shift to relatively cool and dry climate, as indicated by the more positive δ13C values and lower ACL values. During the third stage (1.8-0.3 ka BP), the δ13C, δD, CPI and Paq values showed marked increase and ACL values varied greatly, implying an abrupt change to cold and dry conditions. This climate pattern corresponds to the broad decline in Asian monsoon intensity through the latter part of the Holocene. Our results do not support a later Holocene optimum in south China as suggested by previous studies.

[This corrects the article DOI: 10.1371/journal.pone.0160934.].

Strong wind and heavy rain remain the two most important causes of large acreage wheat (Triticum aestivum L.) lodging in China. For research the influence of wind speed and rainfall-separately as well as together-on the extent and degree of lodging, five levels of the severity of lodging were defined based on a combination of the lodging area and the degree of tilting. Detailed meteorological information was studied on 52 instances of large-scale lodging that occurred from 2007 to 2014. The results showed that strong wind's lodging accounted for 8% of the instances studied, continuous rainfall's lodging accounted for 19% and strong winds-heavy rainfall's accounted for 73%. The minimum instantaneous wind speed that could cause large-scale lodging was closely related to rainfall. Without rainfall, the wind speed that resulted in lodging ranging in severity from slight to severe (Level 2 to Level 5) was 14.9 m/s, 19.3 m/s, 21.5 m/s, and 26.5 m/s, respectively; when accompanied by rainfall, the wind speed that resulted in lodging of the same severity decreased linearly with the increase of rainfall. These results will be particularly useful in preventing and alleviating wheat lodging as well screening wheat varieties with good lodging resistance.

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and high signal-to-noise ratios to fulfill the requirements for 3D brain imaging in vivo. With assistance from density-function theory (DFT) computation, we designed ADLumin-Xs by locking up the rotation of the double bond via fusing the furan ring to the phenyl ring. Our results showed that ADLumin-5 had a high quantum yield of chemiluminescence and could bind to amyloid beta (Aß). Remarkably, ADLumin-5' s radiance intensity in brain areas could reach 4 × 107 photon/s/cm2/sr, which is probably 100-fold higher than most chemiluminescence probes for in vivo imaging. Because of its strong emission, we demonstrated that ADLumin-5 could be used for in vivo 3D brain imaging in transgenic mouse models of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objective: The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents. Summary Background Data: POD occurs in 9% to 50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High-throughput metabolomics using liquid chromatography with tandem mass spectrometry has accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents. Methods: We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y-maze test, open-field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics. Results: Indole-3-propionic acid (IPA) is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA-promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons. Conclusions: Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention. [ABSTRACT FROM AUTHOR]