Internal Rearrangement Research Articles

Study on the structural evolution of polyacrylonitrile fibers in stepwise heat treatment process and its relationship with properties

AbstractThe structural evolution of polyacrylonitrile fibers in stepwise heat treatment process and its relationship with properties were investigated systematically. Results demonstrated that the cyclization degree and dehydrogenation index of fibers reached 84.13% and 1.361, respectively after stabilization at 265°C. The oxygen reaction was enhanced after stabilized at 245°C. Refinement of the microcrystalline structure took effect during stabilization and low temperature carbonization, while growth of microcrystalline dominated during high temperature carbonization. The results of surface topography study not only provided the evolution characteristics of surface microstructure under the influence of chemical reaction, but also further complements the internal aggregation structural rearrangement process from the side. Additionally, the temperature zone from 245 to 265°C was the key stage of the formation of the skin‐core structure, which would be transmitted to the resultant carbon fiber. Tensile strength and tensile modulus decreased during stabilization stage, reaching 4.273 GPa and 221.132 GPa, respectively after high temperature carbonization. The elongation at break which first increased and then decreased proved a toughness failure to brittleness failure. The investigation elucidated the relationship between the mechanical property with chemical and physical microstructure. And the possible rearrangement process of the aggregation structure was proposed.

Novel Tough and Transparent Ultra-Extensible Nanocomposite Elastomers Based on Poly(2-methoxyethylacrylate) and Their Switching between Plasto-Elasticity and Viscoelasticity.

Novel stiff, tough, highly transparent and ultra-extensible self-assembled nanocomposite elastomers based on poly(2-methoxyethylacrylate) (polyMEA) were synthesized. The materials are physically crosslinked by small in-situ-formed silica nanospheres, sized 3–5 nm, which proved to be a very efficient macro-crosslinker in the self-assembled network architecture. Very high values of yield stress (2.3 MPa), tensile strength (3.0 MPa), and modulus (typically 10 MPa), were achieved in combination with ultra-extensibility: the stiffest sample was breaking at 1610% of elongation. Related nanocomposites doubly filled with nano-silica and clay nano-platelets were also prepared, which displayed interesting synergy effects of the fillers at some compositions. All the nanocomposites exhibit ‘plasto-elastic’ tensile behaviour in the ‘as prepared’ state: they display considerable energy absorption (and also ‘necking’ like plastics), but at the same time a large but not complete (50%) retraction of deformation. However, after the first large tensile deformation, the materials irreversibly switch to ‘real elastomeric’ tensile behaviour (with some creep). The initial ‘plasto-elastic’ stretching thus causes an internal rearrangement. The studied materials, which additionally are valuable due to their high transparency, could be of application interest as advanced structural materials in soft robotics, in implant technology, or in regenerative medicine. The presented study focuses on structure-property relationships, and on their effects on physical properties, especially on the complex tensile, elastic and viscoelastic behaviour of the polyMEA nanocomposites.

Clinicopathological and genomic characterization of BCORL1-driven high-grade endometrial stromal sarcomas

BCORL1 is a transcriptional corepressor homologous to BCOR. We describe 12 BCORL1-altered uterine sarcomas with striking resemblance to BCOR-altered endometrial stromal sarcoma (BCOR-ESS), including 5 with BCORL1 rearrangements (JAZF1-BCORL1, EP300-BCORL1, or internal BCORL1 rearrangement), 5 with inactivating BCORL1 mutations (T513fs*22, P600fs*1, R945*, R1196*, or R1265fs*4) and 2 with homozygous BCORL1 deletion. The median patient age was 57.5 years (range 33–79). An association with aggressive clinical behavior was identified. Diagnoses assigned prior to genomic testing varied: 7 tumors were previously diagnosed as ESS, 2 as high-grade uterine sarcomas, 2 as myxoid uterine leiomyosarcomas, and 1 as a uterine spindle cell neoplasm consistent with leiomyosarcoma. Tumors harbored frequent gelatinous, mucomyxoid-like appearance by gross examination and unique histology with morphological overlap with BCOR-ESS. Key microscopic features included (1) a spindle cell appearance, most often with at least focal myxoid stroma, (2) variable amounts of hypocellular fibromyxoid spindle areas with lower grade atypia and/or (3) variable amounts of epithelioid areas with higher grade atypia. Specifically, spindle and epithelioid components were present in 100 and 75% of sarcomas, respectively; myxoid stroma was identified in 83%, collagen plaques or fibrosis in 50%, and high-grade nuclear atypia was present in 42%. Like BCOR-ESS, 50% of BCORL1-altered sarcomas exhibited CDK4 amplification or CDKN2A loss. In contrast, 33% harbored NF1 alterations, while 25% had other alterations in the NF2-mTOR pathway, expanding potential therapeutic targets. In conclusion, inactivating BCORL1 genomic alterations may define a distinct subset of high-grade endometrial stromal sarcomas with biological overlap with BCOR-ESS, both of which may mimic myxoid leiomyosarcomas.

Effect of phosphate ions on the formation of iron oxide/hydroxide as a stabilizer

Hematite (α-Fe2O3) nanoparticles were synthesized using a facile precipitation method under mild conditions by adding phosphate anions (PO43−). The solid-state phase transformation of α-Fe2O3 nanoparticles follows dehydration and internal rearrangement of ferrihydrite initially precipitated at a high pH, while PO43− ions acted as a stabilizer for preventing the dissolution of ferrihydrite. This phase transformation resulted in tiny spherical α-Fe2O3 nanoparticles with a size of approximately 5 ​nm, which is similar to that of the initial ferrihydrite. Conversely, acicular goethite (α-FeOOH) nanoparticles were formed without PO43− ions by dissolution and recrystallization of ferrihydrite. Furthermore, anions such as sulfate (SO42−) and chloride (Cl−) had no significant effect on the α-Fe2O3 formation due to their low Lewis basicity, resulting in an acicular α-FeOOH structure. These results extend the possibility to synthesize α-Fe2O3 nanoparticles, which could have various practical applications.

Multigene phylogeny and taxonomic revision of American shrimps of the genus Cryphiops Dana, 1852 (Decapoda, Palaemonidae) implies a proposal for reversal of precedence with Macrobrachium Spence Bate, 1868.

The freshwater shrimp genus Cryphiops Dana, 1852 has a disjunct distribution in North (Mexico) and South (Brazil, Chile) America, and is composed of only six species. The current classification of genera in the Palaemonidae is controversial, based on variable morphological characters, and still far from a clear definition. Cryphiops differs from the speciose genus Macrobrachium Spence Bate, 1868 only by the absence of the hepatic spines on the carapace. Previous studies with a limited dataset suggested the necessity to link morphology and phylogeny to create an internal rearrangement in the genus to resolve the paraphyletic status. Through a molecular phylogenetic approach, the evolutionary relationships are inferred based on four (mitochondrial and nuclear) genes, among all recognized species of Cryphiops and, in combination with a taxonomic revision, a rearrangement in the systematics of the genus is suggested. The absence of hepatic spines on the carapace, the only character used to separate the genus Cryphiops, is subjective and should be considered as a homoplasy. This implies that Cryphiops and Macrobrachium are subjective synonyms and, because the latter genus is much more diverse and widely known, with several economically important species, to avoid confusion and disturbance in nomenclatural stability and keep universality, a proposal for the priority of the older synonym (Cryphiops) to be partially suppressed in favor of maintaining the prevailing use of the younger synonym (Macrobrachium) is presented. As the species of Cryphiops should be accommodated in the genus Macrobrachium, new names to replace three preoccupied specific names that, by this action, resulted to be secondary homonyms are offered.

Trends in the hyperfine interactions of magnetic adatoms on thin insulating layers

Nuclear spins are among the potential candidates prospected for quantum information technology. A recent breakthrough enabled to atomically resolve their interaction with the electron spin, the so-called hyperfine interaction, within individual atoms utilizing scanning tunneling microscopy (STM). Intriguingly, this was only realized for a few species put on a two-layers thick MgO. Here, we systematically quantify from first-principles the hyperfine interactions of the whole series of 3d transition adatoms deposited on various thicknesses of MgO, NaF, NaCl, h–BN, and Cu2N films. We identify the adatom-substrate complexes with the largest hyperfine interactions and unveil the main trends and exceptions. We reveal the core mechanisms at play, such as the interplay of the local bonding geometry and the chemical nature of the thin films, which trigger transitions between high- and low-spin states accompanied with subtle internal rearrangements of the magnetic electrons. By providing a general map of hyperfine interactions, our work has immediate implications in future STM investigations aiming at detecting and realizing quantum concepts hinging on nuclear spins.

Investigating the effects of process parameters on the filtration performance of ferric hydroxide in a continuous MSMPR reactor

Iron removal in the nickel industry is achieved by precipitation and filtration, and for enhanced process efficiency, the filtration step must be improved. A mixed-suspension-mixed-product-removal (MSMPR) reactor set-up operating at steady-state was established, simulating industrial conditions, and the effect of temperature and residence time on filtration performance of the precipitated akaganéite was investigated. Increasing the reaction temperature and residence time improved the filtration performance, where temperature had the most prominent effect, reducing the specific filter cake resistance with over one order of magnitude from 25 °C to 75 °C. However, there must be a trade-off between temperature increase and cost-effectiveness. A lower moisture content in the filter cakes was also observed with increasing residence time and temperature, which is advantageous in terms of handling of waste and for potential reuse of the iron precipitates. Elevated temperatures resulted in formation of particles with higher crystallinity, lower surface area and higher stability towards aggregation. These particle characteristics were explained by the significant decrease in supersaturation at steady-state at higher temperatures. Variation in residence times, on the other hand, did not affect the solution supersaturation but was still an important parameter on the particle characteristics, which in turn had implications on the filtration performance. The significant changes observed in specific filter cake resistance and filter cake moisture content, but not in supersaturation, with varying residence times were explained by internal rearrangements and locally induced ageing of the particles.

Influence of three types of freezing methods on physicochemical properties and digestibility of starch in frozen unfermented dough

Three types of freezing methods, namely, spiral tunnel freezing method (SF), cryogenic refrigerator freezing method (RF) and liquid nitrogen spray freezing method (LF), were applied to frozen unfermented dough. The particle size distribution and SEM results showed freezing methods reduced the average particle size of starch granules and destroyed the surface microstructure, especially RF, and the damaged starch content and swelling power of starch after treatment increased. Gelatinization and pasting properties of starches changed to varying degrees, indicating freezing methods caused the internal rearrangement of starch molecules. This view could also be inferred from X-ray diffraction (XRD) and Fourier Transform infrared spectroscopy (FT-IR) data. The relative crystallinity (35.51%–38.56%) and the R1047/1022 (0.562–0.590) were increased, compared with the control (32.44%, 0.559, respectively). Meanwhile, freezing treatment improved the digestibility of starch by promoting the combination of enzymes and starch, especially RF. Larger ice crystals formed by RF with slower freezing rate produced larger damage to starch structure, more likely to promote the binding with enzymes. LF with faster freezing rate had less effect on the starch composition than RF and SF with slower freezing rate. The data obtained clarified the influence of freezing methods on the structure and properties of starch in a yeast-free dough system, and enriched the knowledge regarding the effect of freezing technology on food components.

Shared and divergent phase separation and aggregation properties of brain-expressed ubiquilins

The brain-expressed ubiquilins, UBQLNs 1, 2 and 4, are highly homologous proteins that participate in multiple aspects of protein homeostasis and are implicated in neurodegenerative diseases. Studies have established that UBQLN2 forms liquid-like condensates and accumulates in pathogenic aggregates, much like other proteins linked to neurodegenerative diseases. However, the relative condensate and aggregate formation of the three brain-expressed ubiquilins is unknown. Here we report that the three ubiquilins differ in aggregation propensity, revealed by in-vitro experiments, cellular models, and analysis of human brain tissue. UBQLN4 displays heightened aggregation propensity over the other ubiquilins and, like amyloids, UBQLN4 forms ThioflavinT-positive fibrils in vitro. Measuring fluorescence recovery after photobleaching (FRAP) of puncta in cells, we report that all three ubiquilins undergo liquid–liquid phase transition. UBQLN2 and 4 exhibit slower recovery than UBQLN1, suggesting the condensates formed by these brain-expressed ubiquilins have different compositions and undergo distinct internal rearrangements. We conclude that while all brain-expressed ubiquilins exhibit self-association behavior manifesting as condensates, they follow distinct courses of phase-separation and aggregation. We suggest that this variability among ubiquilins along the continuum from liquid-like to solid informs both the normal ubiquitin-linked functions of ubiquilins and their accumulation and potential contribution to toxicity in neurodegenerative diseases.

Changing the Pyramids: The Impact of Broadband Internet on Firm Employment Structures

We study how the introduction of new digital technology affects the occupational and educational structure of firms. Using Brazilian data, we circumvent endogeneity issues by exploiting quasi-random variation in the roll-out of fast internet and a physical constraint in ADSL connectivity. Establishments respond to broadband availability by expanding the share of management and operational positions at the bottom of the firm hierarchy at the expense of other top and middle layers. Furthermore, we observe employment polarization with respect to education. The patterns are complex and more consistent with predictions of organizational theories than with traditional skill-biased technological change or routinization hypotheses. While our findings reveal that broadband may exert distorting effects on labor markets in emerging economies, they also suggest that these internal rearrangements are driven by efficiency-seeking firm behavior and are an important mechanism helping them to survive in the market.

ОСОБЕННОСТИ ВОЗРАСТНОЙ ДИНАМИКИ НЕЙРОНОВ НАРУЖНОГО КОЛЕНЧАТОГО ТЕЛА КОШКИ ПРИ ИСПОЛЬЗОВАНИИ ФРОНТАЛЬНЫХ И САГИТТАЛЬНЫХ СРЕЗОВ

We carried out a comparative morphometric analysis of neurons in the cat dorsal lateral geniculate nucleus (dLGN) in frontal vs. sagittal slices. Using the SMI-32 antibody to non-phosphorylated domains of heavy-chain neurofilaments, the postnatal dynamic of soma parameters (area, roundness, orientation) of dLGN neurons was studied. Measurements were performed in kittens aged 0, 4, 10, 14, 21, 28, 34, 62, 123 days, and in adult cats. A comparison of data obtained in frontal vs. sagittal slices revealed the following significant differences: 1) the soma area of the immunopositive neurons was smaller in frontal vs. sagittal slices in all age groups, and this difference increased with age; 2) the soma orientation was also different in two cutting planes, and a significant age-related change in the soma orientation occurred only in the sagittal, but not frontal, plane. We assume that the difference in the soma area is due to the spatial arrangement of SMI-32-immunopositive neurons in the dLGN, because of which, in the sagittal plane, in contrast to the frontal, neuronal somas were cut parallel to their long axis. In turn, age-related changes in the soma orientation may reflect an internal rearrangement of the dLGN retinotopic organization with age.

Sol–gel synthesis and physical characterization of novel MgCrO4-MgCu2O3 layered films and MgCrO4-MgCu2O3/p-Si based photodiode

Crystalline MgCrO4-MgCu2O3 layered films prepared by the sol–gel process were deposited on glass and p-Si substrates. The films were characterized by XRD, SEM/HR-TEM, and UV–Vis​ optical spectroscopy. A photodiode based on MgCrO4-MgCu2O3/p-Si was assembled and electrically characterized in dark and illumination conditions. Structure and surface morphology investigations demonstrated that the MgCrO4-MgCu2O3 layered films exhibit a higher crystalline structure with a high surface area and a crystallite size of 14 nm. The layered films are opaque in the UV region and transmit light in visible and IR regions. The determined optical band gap is about 3.5 eV independent of the transition types — direct or indirect. In dark conditions, the noted values of the ideality factor, the barrier height, the series resistance of the assembled diode were 1.875, 1.097 eV and 46.72kΩ, respectively. The recognized photocurrent action is driven by traps that lie inside the bandgap. These improvements in structural and optical properties can be attributed to the excellent internal rearrangement and the lower concentration of oxygen vacancy connected with Cr and Cu.

Silicene Growth through Island Migration and Coalescence

Silicene, the Si based counterpart to graphene is predicted to demonstrate similar desirable features to graphene, possessing a Dirac cone in the band-structure and Fermi velocities comparable to graphene. It has also been predicted to demonstrate several exotic properties such as the quantum spin Hall effect, chiral superconductivity and giant magnetoresistance. It has the added benefit of being easy to integrate into current industrial device engineering processes. Silicene monolayers have been grown on Ag (111) and Ir (111) substrates and recently a working field-effect transistor has been demonstrated at room temperature. While it is possible to characterize the final monolayer structure, it is impossible to probe experimentally the evolving atomic structure during growth.We perform massively-parallel molecular dynamics (MD) simulations to study long time monolayer silicene growth on an Ir (111) surface. We observe an intricate multi-stage growth process driven by atomic and cluster migration on the surface. Initial growth involves formation of sub-nanometer clusters via adatom surface diffusion. Subsequently, these clusters rearrange spontaneously with each additional Si atom, forming clusters containing 4–7 member rings. Growth of each cluster through adatom adhesion is accompanied by the formation of larger islands through cluster migration and coalescence. Coalescence of smaller, more mobile islands into larger clusters is aided by the internal rearrangement of rings within each cluster. This flexibility, both of clusters and their constituent atoms, allows the impinging clusters to reorient after first contact and form a more perfect union. We also report on the effect of temperature and flux on the growth process and the final nanostructure. Our study provides atomistic insights into the early stage growth mechanisms of silicene which can be significant for controlled synthesis of its 2D monolayers. Reference: Cherukara, M. J., Narayanan, B., Chan, H., & Sankaranarayanan, S. K. (2017). Silicene growth through island migration and coalescence. Nanoscale, 9(29), 10186-10192. Figure 1

Phosphofructokinase relocalizes into subcellular compartments with liquid-like properties in vivo

Although much is known about the biochemical regulation of glycolytic enzymes, less is understood about how they are organized inside cells. We systematically examine the dynamic subcellular localization of glycolytic protein phosphofructokinase-1/PFK-1.1 in Caenorhabditis elegans. We determine that endogenous PFK-1.1 localizes to subcellular compartments in vivo. In neurons, PFK-1.1 forms phase-separated condensates near synapses in response to energy stress from transient hypoxia. Restoring animals to normoxic conditions results in cytosolic dispersion of PFK-1.1. PFK-1.1 condensates exhibit liquid-like properties, including spheroid shapes due to surface tension, fluidity due to deformations, and fast internal molecular rearrangements. Heterologous self-association domain cryptochrome 2 promotes formation of PFK-1.1 condensates and recruitment of aldolase/ALDO-1. PFK-1.1 condensates do not correspond to stress granules and might represent novel metabolic subcompartments. Our studies indicate that glycolytic protein PFK-1.1 can dynamically form condensates in vivo.

Sol–gel synthesis and physical characterization of high impact polystyrene nanocomposites based on Fe2O3 doped with ZnO

Manufacturing of organic–inorganic composites with enhanced properties particularly, Fe2O3–ZnO/high impact polystyrene (HIPS) nanocomposites promising candidates for many requests. The presence of nanoparticles enhances the structural, thermal, and chemical stabilities, mechanical and operational performance of the nanocomposite matrices. Modified HIPS nanocomposites based on Fe2O3 doped by (0.0–0.6) ZnO were synthesized using the sol–gel method and gel casting approach. The structures, spectroscopic, dielectric and mechanical properties of the synthesized polymeric nanocomposites were investigated by XRD, TEM, FT-IR, UV–vis-DRs, terahertz (THz), dielectric and mechanical analysis. From chemical structural results, it can be confirmed the existence of ZnO in Fe2O3 and the internal structure rearrangement of iron oxide before dispersion into the HIPS matrix. The UV–Vis DRs show that the optical band gap decreases significantly with the increase of ZnO content in the nanocomposite. THz spectra in the spectral range of 0.2–2.5 THz showed an increase in the refractive indices and absorption coefficients for the prepared nanocomposites. Besides, the mechanical properties were affected by the addition of ZnO to HIPS-Fe2O3 where the elongation at break %, Young’s modulus, and maximum strength varied values relying on the applied ratio of ZnO especially for the ratio of 0.4. Finally, the produced nanocomposites can find widespread applications in optoelectronic, chemical, and biological applications besides their feasibility to apply on a large scale.

Kinetic Rejuvenation of Li-Rich Li-Ion Battery Cathodes upon Oxygen Redox

Minimizing internal structural rearrangements upon oxygen redox is currently considered the chief guideline for designing high-performance Li-rich cathodes for Li-ion batteries. In contrast, our st...

Liquid–liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation

Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic-hydrophilic interfaces (e.g., air-water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic-hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid-liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.

Transposable elements contribute to the genome plasticity of Ralstonia solanacearum species complex.

The extensive genetic diversity of Ralstonia solanacearum , a serious soil-borne phytopathogen, has led to the concept that R. solanacearum encompasses a species complex [ R. solanacearum species complex (RSSC)]. Insertion sequences (ISs) are suggested to play an important role in the genome evolution of this pathogen. Here, we identified and analysed transposable elements (TEs), ISs and transposons, in 106 RSSC genomes and 15 Ralstonia spp. We mapped 10 259 IS elements in the complete genome of 62 representative RSSC strains and closely related Ralstonia spp. A unique set of 20 IS families was widespread across the strains, IS5 and IS3 being the most abundant. Our results showed six novel transposon sequences belonging to the Tn3 family carrying passenger genes encoding antibiotic resistance and avirulence proteins. In addition, internal rearrangement events associated with ISs were demonstrated in Ralstonia pseudosolanacearum strains. We also mapped IS elements interrupting avirulence genes, which provided evidence that ISs plays an important role in virulence evolution of RSSC. Additionally, the activity of ISs was demonstrated by transcriptome analysis and DNA hybridization in R. solanacearum isolates. Altogether, we have provided collective data of TEs in RSSC genomes, opening a new path for understanding their evolutionary impact on the genome evolution and diversity of this important plant pathogen.

Exploring the ferroelectric effect of nanocrystalline strontium zinc titanate/Cu: Raman and antimicrobial activity

Nanocrystalline strontium zinc titanate/copper nanoparticle (SZT/Cu) with tetragonal phase was prepared by the acidic sol–gel route and calcined at 700 °C. The phase formation, morphology, and spectroscopic properties of the (SZT/Cu) were investigated via the X-ray diffraction (XRD), field emission scanning electron spectroscopy (FE-SEM), and Raman spectroscopy. Raman spectra reflected the internal rearrangement in the internal structure of strontium zinc titanate (SZT) under the effect of Cu. The dielectric properties of SZT/Cu were investigated over a wide frequency range from 4 Hz to 8 MHz at different temperatures. A ferroelectric behavior with a diffuse phase transition is observed in the behavior of the dielectric constant against temperature. The observed Curie temperature is in the range (40 to 50 °C) with a diffuseness coefficient (α) range from (1.12 to 1.49). The antimicrobial activities of the three prepared samples exhibited antimicrobial activities against Staphylococcus aureus (G+ve bacterium), Escherichia coli (G−ve bacterium), Candida albicans (yeast), and Aspergillus niger (fungus). Strontium zinc titanate doped with 6 mol% of Cu showed higher antimicrobial activities more than the rest samples with inhibition zones of 36, 30, 43 and 47 mm for S. aureus, E. coli, C. albicans, and A. niger, respectively.

Patients with NSCLCs Harboring Internal Inversions or Deletion Rearrangements of the ALK Gene Have Durable Responses to ALK Kinase Inhibitors.

BackgroundALK fusions are targetable drivers in non-small-cell lung cancer (NSCLC). However, patients with NSCLC harboring ALK rearrangements without a fusion partner identified in DNA have also been shown to respond to ALK inhibitors. We aimed to characterize complex ALK variants that may predict sensitivity to multiple approved ALK inhibitors.MethodsComprehensive genomic profiling (CGP) of DNA isolated from formalin‐fixed paraffin‐embedded (FFPE) tumor tissue or blood-based circulating tumor DNA was performed for 39,159 NSCLC patients during routine clinical care. For a subset of cases, RNA sequencing was performed, and prior ALK test results and clinical treatment information were collected from treating physicians.ResultsWe queried the Foundation Medicine NSCLC database and identified ALK internal inversions, as well as internal deletions, as the sole ALK rearrangements in 6 (0.02%) and 3 (0.01%) of cases, respectively. In cases with ALK internal inversions, RNA testing identified an EML4-ALK fusion in 2/2 cases evaluated, and 3/3 patients treated with ALK inhibitors had durable responses. A single patient with an ALK internal deletion and clinical data available responded to multiple ALK inhibitors. RNA data available for a subset of non-NSCLC cases suggest that ALK internal deletions removing a portion of the N-terminus are drivers themselves and do not result in ALK fusions. Fluorescence in situ hybridization (FISH) results were inconsistent for both classes of DNA events.ConclusionRare internal inversions of ALK appear to be indicative of ALK fusions, which can be detected in RNA, and response to ALK inhibitors in patients with NSCLC. In contrast, ALK internal deletions are not associated with ALK fusions in RNA but likely represent targetable drivers themselves. These data suggest that CGP of DNA should be supplemented with immunohistochemistry or RNA-based testing to further resolve these events and match patients to effective therapies.