Unraveling the origin of extra strengthening in gradient nanotwinned metals.

Materials containing heterogeneous nanostructures hold great promise for achieving superior mechanical properties. However, the strengthening effect due to plastically inhomogeneous deformation in heterogeneous nanostructures has not been clearly understood. Here, we investigate a prototypical heterogeneous nanostructured material of gradient nanotwinned (GNT) Cu to unravel the origin of its extra strength arising from gradient nanotwin structures relative to uniform nanotwin counterparts. We measure the back and effective stresses of GNT Cu with different nanotwin thickness gradients and compare them with those of homogeneous nanotwinned Cu with different uniform nanotwin thicknesses. We find that the extra strength of GNT Cu is caused predominantly by the extra back stress resulting from nanotwin thickness gradient, while the effective stress is almost independent of the gradient structures. The combined experiment and strain gradient plasticity modeling show that an increasing structural gradient in GNT Cu produces an increasing plastic strain gradient, thereby raising the extra back stress. The plastic strain gradient is accommodated by the accumulation of geometrically necessary dislocations inside an unusual type of heterogeneous dislocation structure in the form of bundles of concentrated dislocations. Such a heterogeneous dislocation structure produces microscale internal stresses leading to the extra back stress in GNT Cu. Altogether, this work establishes a fundamental connection between the gradient structure and extra strength in GNT Cu through the mechanistic linkages of plastic strain gradient, heterogeneous dislocation structure, microscale internal stress, and extra back stress. Broadly, this work exemplifies a general approach to unraveling the strengthening mechanisms in heterogeneous nanostructured materials.

Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer.

BACKGROUND: Whether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear. METHODS: This population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013-2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories. RESULTS: Two distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07-5.94), pathological tumour Stage (III-IV versus 0-I: OR = 2.52, 95% CI 1.33-4.77), anxiety (OR = 7.58, 95% CI 2.20-26.17), depression (OR = 15.90, 95% CI 4.44-56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01-1.04). CONCLUSIONS: Long-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Impacts of pilot carbon emission trading policies on urban environmental pollution: Evidence from China.

The trading of carbon emissions is a crucial regulatory method to address environmental pollution issues. This study takes China's carbon emission trading pilot policy established in 2013 as a quasi-natural experiment and uses the DID model to empirically test the urban panel data from 2006 to 2019. The results show that the carbon emission trading pilot policy can effectively reduce urban environmental pollution, and this effect is more noticeable in mid-western cities, northern cities, cities with fewer resources, and large-scale cities. In addition, to address the urban environmental pollution problem through this policy, the government is encouraged to raise its environmental protection awareness and put more effort into the innovation of technology. In general, this study uses carbon emission trading policies from China to confirm that market-based incentive environmental regulation tools can effectively reduce environmental pollution in urban areas. These findings can provide more theoretical support and empirical evidence for the government to use mechanisms of the market to effectively solve pollution problems, improve ecological environment quality, and accelerate the realization of green economy.

Anisotropic Nonlocal Damping in Ferromagnet/α-GeTe Bilayers Enabled by Splitting Energy Bands.

The understanding and manipulation of anisotropic Gilbert damping is crucial for both fundamental research and versatile engineering and optimization. Although several works on anisotropic damping have been reported, no direct relationship between the band structure and anisotropic damping was established. Here, we observed an anisotropic damping in Fe/GeTe manipulated by the symmetric band structures of GeTe via angle-resolved photoemission spectroscopy. Moreover, the anisotropic damping can be modified by the symmetry of band structures. Our Letter provides insightful understandings of the anisotropic Gilbert damping in ferromagnets interfaced with Rashba semiconductors and suggests the possibility of manipulating the Gilbert damping by band engineering.

Dynamic Simulation of Nitrifying Microbial Communities for Establishing Acidic Partial Nitritation in Suspended Activated Sludge.

Acidic partial nitritation (PN) is a promising technology to achieve low-cost and energy-efficient shortcut nitrogen removal from wastewater. However, a comprehensive understanding of the acidic PN under dynamic changes of pH in a sequencing batch reactor (SBR) is still lacking. In this study, we successfully established acidic PN (NO2- accumulation ratio >80%) under dynamic pH variation from 7.0 to 4.5 in a lab-scale SBR. By accumulating in situ free nitrous acid (FNA) generation based on the dynamic pH change, acidic PN maintained stability even at a low NH4+ concentration of 100 mg N L-1. The microbial community analysis revealed that two ammonium-oxidizing bacteria (AOB) genera, Nitrosospira and Nitrosomonas, successfully coexisted and cooperated during acidic PN. None of the species of nitrite-oxidizing bacteria (NOB) showed adaptation to intermittent inhibition of in situ FNA even under high DO conditions (>4.0 mg O2 L-1). Furthermore, we innovatively incorporated the classic nitrification model with the growth and decay of different nitrifying bacterial species and their inhibition by pH, FNA, and free ammonia (FA) to predict the nitrifying microbial communities shifting for establishing acidic PN. The extended model was calibrated by using short-term batch experiments and was validated by using long-term dynamic data of the nitrifying microbial community during SBR operation. The validated model was further used to identify feasible influent conditions for the SBR PN process, including influent HCO3- concentration, NH4+ concentration and molar ratio (HCO3/NH4+). Outcomes from this study support the optimal design of acidic PN-based short-cut nitrogen removal processes for future application.

Contribution of flagellar cap gene in virulence and pathogenicity of Aeromonas veronii.

Aeromonas veronii is an important zoonotic and aquatic pathogen that causes a number of illnesses in both humans and animals. It is related to gastroenteritis, skin and soft tissue infections and bacteremia in humans, as well as causing significant economic losses in aquaculture owing to fish sepsis. Here, we constructed the flagellar cap gene (fliD) mutant strain of A. veronii by suicide plasmid-mediated homologous recombination system and analysed its characteristics. It was found that the deletion of fliD had no effect on growth and biochemical properties and could be inherited stably. However, the motility of A. veronii ΔfliD was significantly reduced, the flagellum was defective and the biofilm formation was attenuated compared with that of A. veronii wild-type strain. In vivo experiments revealed that the colonization capacity of ΔfliD was significantly lower than that of the wild-type strain in the period of first 24 h, and the median lethal dose (LD50 ) was 56 times higher than that of the wild-type strain. The Cyprinus carpio infected with the wild-type strain indicated faster death speed and more severe clinical signs compared to ΔfliD strain. These results suggest that fliD is closely related to the virulence of A. veronii and plays an important role in pathogenicity, providing the foundation for pathogenic mechanism studies of A. veronii.

A PET Fluorescent Probe for Dynamic Pd2+ Tracking with Imaging Applications in the Nanofiber and Living Cells.

Constructed on the moiety of a lactam screw ring, a near-infrared fluorescent probe RCya for Pd2+ was designed under the PET mechanism and synthesized by incorporating 2,4-dihydroxybenzaldehyde as the recognition group. Dynamic detection of aqueous Pd2+ by the probe RCya could be accomplished through ion competition, linear response, fluorescence-pH/time stabilities, and other optical tests. Moreover, the high selectivity, low cytotoxicity, cell permeability, and lysosome accumulation properties of RCya enabled the imaging applications on solid-state RCya-PAN composite nanofibers and in living cells. The recognition mechanism of probe RCya toward Pd2+ was further studied through simulation calculation and MS analysis.

An ESIPT-Based Fluorescent Probe for Aqueous Cu+ Detection through Strip, Nanofiber and Living Cells.

Constructed on the benzothiazole-oxanthracene structure, a fluorescent probe RBg for Cu+ was designed under the ESIPT mechanism and synthesized by incorporating amide bonds as the connecting group and glyoxal as the identifying group. Optical properties revealed a good sensitivity and a good linear relationship of the probe RBg with Cu+ in the concentration range of [Cu+] = 0-5.0 µmol L-1. Ion competition and fluorescence-pH/time stability experiments offered further possibilities for dynamic Cu+ detection in an aqueous environment. HRMS analysis revealed a possible 1:1 combination of RBg and Cu+. In addition, colorimetric Cu+ detection and lysosome-targeted properties of the probe RBg were analyzed through RBg-doped PVDF nanofiber/test strips and RBg-Mito/Lyso trackers that were co-stained in living HeLa cells, enabling the probe's future applications as real-time detection methods for dynamic Cu+ tracking in the lysosomes and Cu+ detection under diversified conditions.

Cancer-Related Fatigue After Esophageal Cancer Surgery: Impact of Postoperative Complications.

BACKGROUND: The impact of postoperative complications on cancer-related fatigue is unknown. This nationwide prospective cohort study aimed to assess the trajectory of cancer-related fatigue and the influence of predefined postoperative complications on cancer-related fatigue up to 2 years after esophageal cancer surgery. METHODS: The patients in this study underwent esophagectomy between 2013 and 2019 in Sweden. The exposure was predefined postoperative complications. The outcome was cancer-related fatigue measured by the fatigue scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EORTC QLQ-Fatigue 12 (QLQ-FA12) questionnaire. Linear mixed-effects models provided adjusted fatigue scores and mean score differences (MDs) with 95% confidence intervals (CIs) between patients with and without predefined complications. RESULTS: The study enrolled 331 patients. The QLQ-C30 fatigue score increased with clinical relevance among patients with any complications (MD, 5.8; 95% CI, 2.6-9.0) who had a higher Clavien-Dindo classification (grades 2 to 3a: MD, 7.3; 95% CI, 3.1-11.5), a medical complication (MD, 6.9; 95% CI, 3.0-10.7), or a pulmonary complication (MD, 6.9; 95% CI, 2.1-11.6) for 1-1.5 years and remained stable until 2 years after esophagectomy. Similar patterns were found in the QLQ-FA12 fatigue and QLQ-FA12 physical and emotional subscales, but not in the cognitive subscales. CONCLUSIONS: Complications in general and medical and pulmonary complications in particular might be associated with increased cancer-related fatigue after esophagectomy.

Body Mass Index-Adjusted Weight Loss Grading System and Cancer-Related Fatigue in Survivors 1 Year After Esophageal Cancer Surgery.

BACKGROUND: The association between pre- and postoperative weight loss and cancer-related fatigue after esophageal cancer surgery is unclear. This nationwide, prospective, longitudinal cohort study aimed to assess the influence of weight loss on cancer-related fatigue among esophageal cancer survivors. METHODS: Patients who underwent esophagectomy for cancer between 2013 and 2019 in Sweden were enrolled in this study. Exposure was measured by the body mass index-adjusted weight loss grading system (WLGS). Cancer-related fatigue was assessed using the fatigue scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EORTC QLQ-Fatigue 12 (QLQ-FA12) questionnaire measuring overall fatigue and physical, emotional, and cognitive fatigue. Growth mixture models were used to identify unobserved trajectories of cancer-related fatigue. Multivariable linear and logistic regression models were fitted to assess the associations between WLGS and cancer-related fatigue, adjusting for potential confounders. RESULTS: Three trajectories were identified-low, moderate, and severe persistent fatigue. Cancer-related fatigue remained stable in each trajectory between 1 and 3 years after esophagectomy. Among the 356 enrolled patients, 4.5-22.6% were categorized into the severe persistent fatigue trajectory in terms of QLQ-C30 (19.9%), FA12 overall (10.5%), physical (22.6%), emotional (15.9%), and cognitive fatigue (4.5%). No association between pre- or postoperative WLGS and cancer-related fatigue was found between 1 and 3 years after esophageal cancer surgery. CONCLUSIONS: Weight loss did not seem to influence cancer-related fatigue after esophageal cancer surgery.

Contribution of prgH gene for Salmonella Pullorum to virulence and the expression of NLRP3, Caspase-1 and IL-1ß in chickens.

Type III secretion system 1 (T3SS1) encoded by Salmonella pathogenicity island 1 (SPI1) is associated with invasion of host cells by Salmonella, PrgH encoded by prgH gene is an important component of T3SS1. This study aimed to explore the contribution of prgH gene for Salmonella Pullorum to virulence and the expression of NLRP3, Caspase-1 and IL-1ß in chickens. A prgH gene deletion mutant (C79-13ΔprgH) was firstly generated, and the result of LD50 showed that deletion of prgH significantly decreased the virulence of Salmonella Pullorum in one-day-old HY-line white chickens, and the colonization also decreased in chickens after loss of prgH. Next, the expressions of NLRP3, Caspase-1, and IL-1ß were detected in acute infection model of chickens by qRT-PCR and/or ELISA, respectively, and the results showed that the mutant strain C79-13ΔprgH reduced the expression levels of NLRP3, Caspase-1, and IL-1ß in chickens compared to the group infected with the wild type strain C79-13. Taken together, all of these findings indicated that prgH promotes the virulence and the expression of NLRP3, Caspase-1, and IL-1ß for Salmonella Pullorum in chickens.

Update on surgical repair in functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is common in patients with myocardial infarction or dilated cardiomyopathy, and portends a poor prognosis despite guideline-directed medical therapy (GDMT). Surgical or transcatheter mitral repair for FMR from recent randomized clinical trials showed disappointing or conflicting results. AIMS: To provide an update on the role of surgical repair in the management of FMR. MATERIALS AND METHODS: A literature search was conducted utilizing PubMed, Ovid, Web of Science, Embase, and Cochrane Library. The search terms included secondary/FMR, ischemic mitral regurgitation, mitral repair, mitral replacement, mitral annuloplasty, transcatheter mitral repair, and percutaneous mitral repair. Randomized clinical trials over the past decade were the particular focus of the current review. RESULTS: Recent data underlined the complexity and poor prognosis of FMR. GDMT and cardiac resynchronization, when indicated, should always be applied. Accurate assessment of the interplay between ventricular geometry and mitral valve function is essential to differentiate proportionate FMR from the disproportionate subgroup, which could be helpful in selecting appropriate transcatheter intervention strategies. Surgical repair, most commonly performed with an undersized ring annuloplasty, remains controversial. Adjunctive valvular or subvalvular repair techniques are evolving and may produce improved results in selected FMR patients. CONCLUSION: FMR resulted from complex valve-ventricular interaction and remodeling. Distinguishing proportionate FMR from disproportionate FMR is important in exploring their underlying mechanisms and to guide medical treatment with surgical or transcatheter interventions. Further studies are warranted to confirm the clinical benefit of appropriate surgical repair in selected FMR patients.

[Representations of object animacy and real-world size in the ventral visual pathway].

How the brain perceives objects and classifies perceived objects is one of the important goals of visual cognitive neuroscience. Previous research has shown that when we see objects, the brain's ventral visual pathway recognizes and classifies them, leading to different ways of interacting with them. In this paper, we summarize the latest research progress of the ventral visual pathway related to the visual classification of objects. From the perspective of the neural representation of objects and its underlying mechanisms in the visual cortex, we summarize the current research status of the two important organizational dimensions of object animacy and real-world size, provide new insights, and point out the direction of further research.

Salmonella Pullorum lacking srfA is attenuated, immunogenic and protective in chickens.

Sallmonella Pullorum is a host-restricted pathogen for poultry and causes severe economic importance in many developing countries. The development of novel vaccines for Salmonella Pullorum is necessary to eradicate the prevalence of the pathogen. In our study, a srfA deletion mutant (C79-13ΔsrfA) of Salmonella Pullorum was constructed, and then the biological characteristics and protective efficacy of the mutant were evaluated. The mutant C79-13ΔsrfA was much less virulent than its parental strain C79-13 in one-day-old HY-line white chickens, immunization with C79-13ΔsrfA (4 × 107 CFU) through oral pathway induced highly specific humoral and cellular immune responses, the growth performance of vaccinated chickens was consistent with that of unvaccinated chickens. The survival percentages of vaccinated chickens reached 90% and 80%, after challenge with Salmonella Pullorum strain C79-13 and Salmonella Gallinarum strain SG9 at 10 days post-immunization (dpi), respectively. Collectively, our results indicate that C79-13ΔsrfA is a live attenuated vaccine candidate.

Single-stage few-cycle nonlinear compression of milliJoule energy Ti:Sa femtosecond pulses in a multipass cell.

We report on the nonlinear temporal compression of mJ energy pulses from a Ti:Sa chirped pulse amplifier system in a multipass cell filled with argon. The pulses are compressed from 30 fs down to 5.3 fs, corresponding to two optical cycles. The post-compressed beam exhibits excellent spatial quality and homogeneity. These results provide guidelines for optimizing the compressed pulse quality and further scaling of multipass-cell-based post-compression down to the single-cycle regime.

Novel germline mutation KMT2A G3131S confers genetic susceptibility to familial myeloproliferative neoplasms.

The current study analyzed the clinical and genetic characteristics of a family with familial myeloproliferative neoplasms (MPNs). Whole-exome sequencing was conducted, and a germline heterozygous mutation in lysine methyltransferase 2A (KMT2A, also known as MLL1), G3131S (c.9391G > A, p.Gly3131Ser, rs150804738), was identified. Somatic DNA and germline DNA were collected from 8 family members, 120 healthy donors (somatic DNA), and 30 healthy donors (germline DNA). Using Sanger sequencing, the KMT2A G3131S mutation was analyzed. Four individuals, the proband (II-1), his sister (patient II-2), and family members II-3 and III-1 (somatic DNA and germline DNA), tested positive for the KMT2A G3131S mutation. We did not observe the KMT2A G3131S mutation in healthy donors (somatic DNA and germline DNA), indicating that this is not a SNP. Bioinformatics analysis of KMT2A G3131S suggested that protein structure changes could be caused by this mutation. To further elucidate the function of KMT2A G3131S, the CRISPR-Cas9 technique was applied to generate a KMT2A G3131S heterozygous K562 cell line. The colony formation potency, apoptosis, and cell cycle of KMT2A G3131S mutant K562 cells were analyzed. The results demonstrated that KMT2A G3131S mutant K562 cells showed increased proliferation and colony formation ability. Immunophenotyping was performed using flow cytometry to analyze the surface marker expression of gene-edited KMT2A G3131S mutant K562 cells. A significant increase in CD11b and mild increases in CD61 and CD235a were observed in KMT2A G3131S mutant K562 cells, suggesting that the KMT2A G3131S mutant could cause an increase in myeloproliferation. May-Giemsa staining showed that the morphological changes in KMT2A G3131S mutant K562 cells were consistent with the flow cytometry analysis. To verify which downstream genes were affected by the KMT2A G3131S mutant, we performed real-time PCR to evaluate the expression of previously reported KMT2A-related genes and found that C-MYB expression was significantly decreased. Western blotting was applied to investigate the expression of Kmt2a and C-myb proteins, and the results showed that in KMT2A G3131S mutant K562 cells, the expression of C-myb was decreased. Our findings suggested that KMT2A G3131S could affect the myeloproliferation of K562 cells and decrease C-myb expression. In conclusion, KMT2A G3131S could be considered a novel genetic susceptibility gene in familial MPN.

Identification and characterization of isocitrate dehydrogenase 1 (IDH1) as a functional target of marine natural product grincamycin B.

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.

Evaluation of Fluorescent Cu2+ Probes: Instant Sensing, Cell Permeable Recognition and Quantitative Detection.

By incorporating a rhodamine spirolactam structure as the recognition site for Cu2+, two novel probes were synthesized through a connection of rhodamine 6G acylhydrazine and 5-formyl-6-hydroxyl-4-methylcoumarin/2,4-dihydroxybenzaldehyde. In the recognition process of probes towards Cu2+, the spirolactam ring exhibited opening and closing, accompanying an instant and specific change in fluorescence and in color, which could also achieve a naked-eye and semiquantitative recognition of aqueous Cu2+ besides the fluorescent Cu2+ detection method. Fluorescent analyses and ECV304 cell imaging further revealed the probes' good optical stability, instant response, low toxicity, and membrane permeability, which offers future possibilities for the probes' instant detection and the real-time tracking of Cu2+ in biological systems.

A novel NAP1L4/NUTM1 fusion arising from translocation t(11;15)(p15;q12) in a myeloid neoplasm with eosinophilia and rearrangement of PDGFRA highlights an unusual clinical feature and therapeutic reaction.

NUT midline carcinoma (NMC) is an aggressive neoplasm and mainly involved in the head and neck area. The defining genetic hallmark on these tumors is that testis-specific nuclear gene (NUTM1) fuses to bromodomain protein family member 4 gene (BRD4), resulting in the formation of BRD4-NUTM1 transcript. Here, we report a case with myeloid neoplasm complicating with eosinophilia (MLN-Eo) and rearrangement of PDGFRA, which co-exists with a new nucleosome assemble protein 1-like 4 gene (NAP1L4) NAP1L4-NUTM1 fusion. The patient have unusually clinical features and therapeutic reaction to imatinib mesylate. The cloned NAP1L4-NUTM1 gene structure is also determined.