Majority Of Nuclei Research Articles

Green's function method for the single-particle resonances in a deformed Dirac equation

Single-particle resonances are crucial for exotic nuclei near and beyond the drip lines. Since the majority of nuclei are deformed, the interplay between deformation and orbital structure near threshold becomes very important and can lead to an improved description of exotic nuclei. In this work, the Green's function (GF) method is applied to solve the coupled-channel Dirac equation with quadrupole-deformed Woods-Saxon potentials for the first time. The detailed formalism for the partial-wave expansion of the Green's function is presented. A new approach getting exact values for energies and widths of resonant states by the GF method is proposed. Numerical checks are carried out by comparing with our previous implementation of the spherical GF method and the results from the deformed complex momentum representation~(CMR), the analytical continuation of the coupling constant (ACCC), and the scattering phase shift (SPS) methods, and it is proved that the GF method is very effective and reliably for describing resonance states, no matter they are narrow or broad, spherical or deformed. Finally, Nilsson levels for bound and resonant orbitals in the halo candidate nucleus $^{37}$Mg are calculated from the deformed GF method over a wide range of deformations and some decisive hints of $p$-wave halo formation are shown in this nucleus, namely, the crossing between the configurations $1/2[321]$ and $5/2[312]$ at deformation parameter $\beta>0.5$ may enhance the probability to occupy the $1/2[321]$ orbital that is originated from the $2p_{3/2}$ shell.

Single-cell RNA sequencing in facioscapulohumeral muscular dystrophy disease etiology and development.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by sporadic de-repression of the transcription factor DUX4 in skeletal muscle. DUX4 activates a cascade of muscle disrupting events, eventually leading to muscle atrophy and apoptosis. Yet, how sporadic DUX4 expression leads to the generalized muscle wasting remains unclear. Transcriptome analyses have systematically been challenged by the majority of nuclei being DUX4neg, weakening the DUX4 transcriptome signature. Moreover, DUX4 has been shown to be expressed in a highly dynamic burst-like manner, likely resulting in the detection of the downstream cascade of events long after DUX4 expression itself has faded. Identifying the FSHD transcriptome in individual cells and unraveling the cascade of events leading to FSHD development may therefore provide important insights in the disease process. We employed single-cell RNA sequencing, combined with pseudotime trajectory modeling, to study FSHD disease etiology and cellular progression in human primary myocytes. We identified a small FSHD-specific cell population in all tested patient-derived cultures and detected new genes associated with DUX4 de-repression. We furthermore generated an FSHD cellular progression model, reflecting both the early burst-like DUX4 expression as well as the downstream activation of various FSHD-associated pathways, which allowed us to correlate DUX4 expression signature dynamics with that of regulatory complexes, thereby facilitating the prioritization of epigenetic targets for DUX4 silencing. Single-cell transcriptomics combined with pseudotime modeling thus holds valuable information on FSHD disease etiology and progression that can potentially guide biomarker and target selection for therapy.

NEW GENES, FUNCTIONS AND BIOMARKERS: O.4Single-cell RNA-sequencing in facioscapulohumeral muscular dystrophy disease: etiology and development

Facioscapulohumeral muscular dystrophy (FSHD) is hallmarked by the sporadic expression of the germline and cleavage-stage transcription factor DUX4 in myonuclei of affected muscle. Despite the sporadic nature of DUX4 expression, its presence in muscle activates a cascade of muscle disrupting events eventually leading to muscle atrophy and apoptosis of affected cells. Yet, with an estimated ratio of 1:100 - 1:1000 nuclei expressing DUX4 in primary myotube cultures, transcriptome analyses have systematically been challenged by the majority of nuclei being negative for DUX4 expression, weakening the DUX4 transcriptome signatures. More elaborate analysis of the FSHD-transcriptome has thus far been facilitated by DUX4-overexpression or DUX4-reporter systems biasing the data towards DUX4-associated pathways and limiting the analysis of non-cell autonomous effects. Identifying the ``pure'' FSHD transcriptome, i.e. including the study of cell-autonomous and non-cell autonomous DUX4 effects, and unraveling the cascade of events leading to FSHD development, has so far been very difficult. We employed single-cell RNA-sequencing (scRNAseq), combined with pseudotime trajectory modeling, to study FSHD disease etiology and cellular progression in human patient-derived primary myocytes. We identified a small FSHD-specific cell population in all 4 tested FSHD patient-derived primary cultures and detected promising new genes that are likely related to direct and indirect effects of DUX4. Furthermore, capitalizing on the heterogeneity in cellular state in FSHD cell cultures, we employed pseudotime trajectory modeling to generate detailed insights into FSHD etiology and cellular progression. We expect that pseudotime trajectories like our FSHD pseudotime model hold invaluable information not only for studying disease etiology, development and progression, but also for biomarker identification and therapeutic target selection

Special features of the structure of the beta-stability line for nuclei

The mass-number (A) dependence Z β(A) for nuclei lying on the beta-stability line (BSL) is calculated for A and Z values in the ranges of A = 2–258 and Z = 1–100, respectively. The calculated values are compared with experimental data. The deviations ΔZ = Z expt − Z β are analyzed. This analysis of ΔZ reveals that there are three regions of A values in which the A dependence of ΔZ is parabolic. The possible forms of the A dependence of ΔZ are analyzed, and it is shown that the majority of nuclei belong to several parabolas simultaneously.

BCR-ABL1 gene rearrangement as a subclonal change in ETV6-RUNX1–positive B-cell acute lymphoblastic leukemia

AbstractWe report here on a case of ETV6-RUNX1–positive B-cell acute lymphoblastic leukemia (B-ALL) that has acquired a BCR-ABL1 gene rearrangement as a subclonal change. The 19-year-old female patient presented with B symptoms, pancytopenia, and circulating blasts. The bone marrow aspirate was hypercellular and was infiltrated by an immature blast population that was confirmed as B-ALL by flow cytometry. Sequential fluorescent in situ hybridization was performed on the patient's leukemic cells, which were shown to contain both ETV6-RUNX1 and BCR-ABL1 gene rearrangements. The majority of nuclei (85%) showed only the ETV6-RUNX1 gene rearrangement; however, an additional 10% also showed a variant BCR-ABL1 gene rearrangement, indicating the ETV6-RUNX1 gene rearrangement was the primary change. A review of the literature has shown that acquisition of a BCR-ABL1 gene rearrangement as a secondary change in B-ALL is a very rare occurrence, and the effect it may have on prognosis is uncertain in the modern therapy age.

Nuclear organisation of some immunohistochemically identifiable neural systems in five species of insectivore—Crocidura cyanea, Crocidura olivieri, Sylvisorex ollula, Paraechinus aethiopicus and Atelerix frontalis

The organization of the cholinergic, catecholaminergic, and serotonergic neurons in the brains of five species of insectivores and the orexinergic (hypocretinergic) system in four insectivore species is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of other mammalian species. Brains of insectivores were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The majority of nuclei were similar among the species investigated and to mammals in general, but certain differences in the nuclear complement highlighted potential phylogenetic interrelationships. In the cholinergic system, the three shrew species lacked parabigeminal and Edinger–Westphal nuclei. In addition, the appearance of the laterodorsal tegmental nucleus in all insectivores revealed a mediodorsal arch. All three of these features are the same as those present in microchiropterans. The catecholaminergic system of the three shrew species lacked the A4 and A15d nuclei, as well as having an incipient A9v nucleus, again features found in microchiropteran brains. The serotonergic and orexinergic systems of the insectivores are similar to those seen across most eutherian mammals. The analysis of similarities and differences across mammalian species indicates a potential phylogenetic relationship between the Soricidae (shrews) and the microchiropterans.

Analytical continuation from bound to resonant states in the Dirac equation with quadrupole-deformed potentials

Background: Resonances with pronounced single-particle characteristics are crucial for quantitative descriptions of exotic nuclei near and beyond the drip lines, and often impact halo formation and nucleon decay processes. Since the majority of nuclei are deformed, the interplay between deformation and orbital structure near threshold can lead to improved descriptions of exotic nuclei.Purpose: Develop a method to study single-particle resonant orbital structure in the Dirac equation with a quadrupole-deformed Woods-Saxon potential. Determine the structure evolution of bound and resonant levels with deformation in this scheme, and examine the impact on halo formation in loosely bound systems, with a focus on the recent halo candidate nucleus $^{37}\mathrm{Mg}$.Method: Analytical continuation of the coupling constant (ACCC) method is developed on the basis of the Dirac equation with a deformed Woods-Saxon potential. The scalar and vector terms in the deformed potential are determined by the energies of the valence neutron and nearby orbitals, which are extracted from a self-consistent relativistic Hartree-Bogoliubov (RHB) calculation with the PC-PK1 density functional.Results: We compare the energies and widths of resonant orbitals in the recent halo nucleus candidate $^{37}\mathrm{Mg}$ using the ACCC method based on the Dirac coupled-channel equations with those determined from the scattering phase shift (SPS) method. It is found that the results from the two methods agree well for narrow resonances, whereas the SPS method fails for broad resonances. Nilsson levels for bound and resonant orbitals from the ACCC method are calculated over a wide range of deformations and show some decisive hints of halo formation in $^{37}\mathrm{Mg}$.Conclusions: In our ACCC model for deformed potentials in the coupled-channel Dirac equations, the crossing of the configuration $1/2[321]$ and $5/2[312]$ orbitals at a deformation of approximately 0.5 enhances the probability to occupy the $1/2[321]$ orbital coming from $2{p}_{3/2}$ thereby explaining the recent observation of a $\mathit{p}$-wave one-neutron halo configuration in $^{37}\mathrm{Mg}$. The resonant $1/2[301]$ configuration plays a crucial role in halo formation in the magnesium isotopes beyond $A=40$ for a wide range of deformations larger than 0.2.

Poster #M34 FUNCTIONAL DYSCONNECTION IN THE FIRST EPISODE OF SCHIZOPHRENIA AND IN REMISSION

Three clones for chicken chromobox proteins were obtained from liver and ovary cDNA libraries. pCHCB1 and pCHCB2 encode polypeptides showing 96 and 95% identity with mouse M31 and M32, respectively, which are homologues ofDrosophilaheterochromatin protein 1 (HP1), and pCHCB3 encodes a polypeptide whose sequences of chromobox and C-terminal region show high-level similarities with those of mouse M33,Drosophilapolycomb (Pc) protein, andXenopusPc homologue. When these cDNAs were expressed in female chicken embryonic fibroblasts (CEFs) as GFP-fused or HA-tagged proteins, all three proteins were found to be localized in nuclei. Among them, CHCB1 associates with brightly stained spots with 4′, 6-diamidino-2-phenylindole (DAPI), suggesting its accumulation on heterochromatins. One of those spots was identified asW-heterochromatin. When CHCB1 lacking the N-terminal basic/acidic region or a part of the chromobox region was overexpressed in CEFs,W-heterochromatin became partially or extensively decondensed in the majority of nuclei. Overexpression of CHCB3 lacking a part of the chromobox did not cause decon-densation ofW-heterochromatin. Specific antisera raised against a part of CHCB1 or CHCB2, produced inEscherichia coli,detected protein species having apparent molecular masses of 25 kDa or 22 plus 23 kDa, respectively, in the subnuclear fraction containing the majority of chromatin from female chicken MSB-1 cells.

Distribution of parvalbumin, calbindin and calretinin containing neurons and terminal networks in relation to sleep associated nuclei in the brain of the giant Zambian mole-rat (Fukomys mechowii)

To broaden the understanding of the neural control and evolution of the sleep–wake cycle in mammals, the distribution and interrelations of sleep associated nuclei with neurons and terminal networks expressing the calcium-binding proteins parvalbumin, calbindin and calretinin were explored in a rodent that lacks a significant visual system. The sleep-associated nuclei explored include the cholinergic basal forebrain and pontine nuclei, the catecholaminergic locus coeruleus complex, the serotonergic dorsal raphe nuclear complex, the hypothalamic orexinergic nuclei, and the thalamic reticular nucleus. Zambian mole-rat brains were sectioned and stained in a one in nine series for Nissl, myelin, choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5HT), orexin (OrxA), calbindin (CB), calretinin (CR) and parvalbumin (PV). We observed that while the density of immunopositive calbindin (CB+) neurons and terminal networks varied in the different sleep related nuclei, they were found in all nuclei apart from the compact and diffuse subdivisions of the subcoeruleus, which lacked CB+ neurons but evinced a CB+ terminal network. The density of calretinin immunopositive (CR+) neurons and terminal networks varied between the sleep related nuclei, but was present in all nuclei examined. Neurons and terminal networks associated with PV immunoreactivity were the most sparsely distributed in these nuclei, but were present in the majority of nuclei. The thalamic reticular nucleus had the highest density of PV+ neurons and terminal networks, while PV+ neurons were absent in the cholinergic pontine nuclei, and PV+ neurons and terminal networks were absent in the orexinergic nuclei. The increased presence of neurons and terminal networks expressing the calcium binding proteins in comparison to that seen in the laboratory rat, specifically in the brainstem, may account for the prominent muscle twitches during REM sleep previously observed in this subterranean African rodent.

DNA Underreplication in the Majority of Nuclei in the Drosophila Melanogaster Thorax: Evidence from Suur and Flow Cytometry

The discovery of endoreduplication in the majority of cells of the thorax of Drosophila has implications for genomics, transcriptome levels, chromatin structure and life history of these model insects. The ratio of 2C/4C DNA amounts is 2.00 for nuclei from the head, yet is 1.75 and 1.83 for nuclei from the thorax of wild type and suppressor of underreplication (SuUR) strains, respectively. The latter ratios reflect underreplication in the majority of nuclei from the thorax, which is only partially suppressed in the SuUR strain. The effect is age-dependent. Thoracic 4C DNA is significantly more underreplicated in the nuclei of 10 day old than newly emerged flies. The consequences of underreplication for the majority of thoracic cell nuclei, likely mimic those in highly endoreduplicated polytene salivary and nurse cell nuclei, which would affect expression levels in genomic, transcriptomic, methalomic and other studies based wholly or in part on Drosophila thoracic nuclei.

THE ACS FORNAX CLUSTER SURVEY. VI. THE NUCLEI OF EARLY-TYPE GALAXIES IN THE FORNAX CLUSTER

The Advanced Camera for Surveys (ACS) Fornax Cluster Survey is a Hubble Space Telescope program to image 43 early-type galaxies in the Fornax cluster, using the F475W and F850LP bandpasses of the ACS. We employ both 1D and 2D techniques to characterize the properties of the stellar nuclei in these galaxies, defined as the central "luminosity excesses" relative to a Sersic model fitted to the underlying host. We find 72+/-13% of our sample (31 galaxies) to be nucleated, with only three of the nuclei offset by more than 0.5" from their galaxy photocenter, and with the majority of nuclei having colors bluer than their hosts. The nuclei are observed to be larger, and brighter, than typical Fornax globular clusters, and to follow different structural scaling relations. A comparison of our results to those from the ACS Virgo Cluster Survey reveals striking similarities in the properties of the nuclei belonging to these different environments. We briefly review a variety of proposed formation models and conclude that, for the low-mass galaxies in our sample, the most important mechanism for nucleus growth is probably infall of star clusters through dynamical friction, while for higher mass galaxies, gas accretion triggered by mergers, accretions and tidal torques is likely to dominate, with the relative importance of these two processes varying smoothly as a function of galaxy mass. Some intermediate-mass galaxies in our sample show a complexity in their inner structure that may be the signature of "hybrid nuclei" that arose through parallel formation channels.

Deformation-twinning-related features of primary recrystallization of (110)[001] single crystals of the Fe-3% Si-0.5% Cu alloy

In the regions of the deformed cube-on-edge single crystal of the Fe-3% Si-0.5% Cu alloy with an enhanced density of deformation twins, the nucleation of new grains during primary recrystallization (PR) occurs via several mechanisms. The majority of nuclei of PR are formed on twins as on substrates. The newly formed grains of PR are characterized by the presence of a cube-on-edge texture and are in special misorientations of the Σ3 type with respect to the twin orientation and of the Σ9 (Σ27) type with respect to the octahedral matrix. The mechanism of the formation of nucleation centers for PR on the twins as on substrates can be a splitting of the nonequilibrium special boundary Σ3. A significant role of special misorientations in the formation of the Goss texture upon PR has been shown experimentally.

Duplication of Philadelphia chromosome and trisomy of chromosome 21 in a pediatric patient with acute lymphoblastic leukemia

The evaluation of molecular and cytogenetic characteristics using novel techniques has significantly contributed into the insight of leukemia. In this study, immunoglobulin heavy chain gene rearrangements (V(H)D(H)J(H) region) were analyzed by polymerase chain reaction (PCR). Point mutations of the D835/I836 in the activation loop (AL) domain of the second tyrosine kinase domain of the fms-related tyrosine kinase 3 (FLT3) gene and NRAS (neuroblastoma cell line) point mutations were also analyzed by PCR. Furthermore, sequence analysis of the V(H)D(H)J(H) region was performed, as well as, chromosomal aberrations were identified by interphase fluorescence in situ hybridization (iFISH) in a 12.5-year-old boy with acute lymphoblastic leukemia. Positive MRD was found in bone marrow samples obtained at various time points during and after treatment completion prior to relapse. Molecular analysis of the FLT3 gene mutations revealed an acquired a G → T mutation at codon 835, which resulted to substitution of aspartate 835 for tyrosine (D835Y). Cytogenetic analysis with iFISH showed t(9;22) (q34;q11.2), with minor-BCR/ABL1 fusion gene in the majority of nuclei, while a subclone with duplication of the Philadelphia chromosome was observed. Triple signals of AML1 were detected in 80% of nuclei, which were compatible with trisomy of chromosome 21. BCR/ABL1 fusion gene, duplication of Philadelphia chromosome and persistence of MRD constitute inferior prognostic factors, while hyperdiploidy, trisomy of chromosome 21 and FLT3-AL mutations are related to better prognosis. The study of cytogenetic and molecular characteristics is essential in order to decide on the optimal treatment protocol in childhood leukemia.

Nuclear masses near the proton drip-line and their impact on nucleosynthesis in explosive stars

The interplay of the fundamental forces (here mainly the strong force and electromagnetic force) holds nucleons together to form atomic nuclei. However, in nature only less than ten percent of the total number of nuclei is stable. The majority of nuclei are unstable; that is, after having lived for a certain time, they change into the daughter nuclei by radioactive decay. The familiar decay types that can be found in most parts of the chart of nuclide are α-decay and β-decay. There are other important processes in which unstable nuclei can change into other ones. These occur, for example, in very neutronrich or proton-rich regions of the chart of nuclide. There are boundaries called drip-lines, which are the lines on the Z (proton)-N (neutron) plane where the nucleon separation energy is zero. The nuclear binding becomes weaker and weaker when moving from the stable region towards the drip-lines, and eventually no nucleus can exist beyond the drip-lines. Taking the proton-rich region as an example, near the proton drip-line, protons are only weakly bound and a proton radioactivity can occur. Also because of the small binding, nuclei near the proton drip-line may capture additional protons and become new, heavier nuclides if the capture conditions are present. Detailed knowledge on the nucleon-capture processes lies at the heart of the understanding of nucleosynthesis in the Universe——a very fundamental but unanswered question about how the heavy elements (i.e. those heavier than iron) are created. In order for nuclei to capture protons, a high temperature environment (usually above 1×10 9 K) is needed so that they can overcome the large coulomb barrier for charged particle reactions. A hydrogen rich

NO-Positive Neurons in Some Nuclei of Human Bulbar Vasomotor Center in Arterial Hypertension

The distribution of nitroxidergic neurons and activities of neuronal NO synthase in them in some nuclei of the bulbar vasomotor center were studied in patients with early forms of arterial hypertension. Activity of neuronal NO synthase is reduced significantly in the majority of nuclei in patients with early forms of arterial hypertension, while the content of NO-positive cells was only slightly changed. More pronounced changes in this parameter were detected in the solitary tract nuclei in comparison with the reticular formation nuclei, which had efferent relationships with the intermediate lateral spinal nucleus.

Gallbladder Epithelial Cells that Engraft in Mouse Liver Can Differentiate into Hepatocyte-Like Cells

We tested the hypothesis that well-differentiated gallbladder epithelial cells (GBECs) are capable of engrafting and surviving in murine liver and acquire phenotypic characteristics of hepatocytes. GBECs isolated from transgenic mice that constitutively express green fluorescent protein (GFP) were either cultured before transplantation or transplanted immediately following isolation. Recipient mice with severe-combined immunodeficiency underwent retrorsine treatment and either partial hepatectomy before transplantation or carbon tetrachloride treatment following transplantation. From 1 to 4 months following transplantation, the livers of recipient mice contained discrete colonies of GFP(+) cells. Most GFP(+) cells surrounded vesicles, were epithelial cell-like in morphology, and expressed the biliary epithelial markers cytokeratin 19 and carbonic anhydrase IV. Subpopulations of GFP(+) cells resembled hepatocytes morphologically and expressed the hepatocyte-specific markers connexin-32 and hepatic nuclear factor-4alpha, but not cytokeratin 19 or carbonic anhydrase IV. At 4 months, cells in GFP(+) colonies were not actively proliferating as determined by proliferating cell nuclear antigen expression. Thus, GBECs are capable of engrafting and surviving in damaged mouse livers, and some can differentiate into cells with hepatocyte-like features. These findings suggest that environmental cues in the recipient liver are sufficient to allow a subpopulation of donor GBECs to differentiate into hepatocyte-like cells in the absence of exogenous transcriptional reprogramming. GBECs might be used as donor cells in a cell transplantation approach for the treatment of liver disease.

Effects of ethanol on pancreatic beta-cell death: interaction with glucose and fatty acids

Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic beta-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on beta-cell survival and metabolism. We treated the rat beta-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen species (ROS) were determined by (5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst 33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and affect mitochondrial function in RINm5F beta-cells. However, ethanol causes beta-cell death by apoptosis, whereas fatty acids cause cell death predominantly by necrosis. It is not known whether these results are applicable to human beta-cells.

Shear-induced nonisothermal crystallization of low-density polyethylene

The effect of melt memory on the shear-induced nonisothermal crystallization of a low-density polyethylene melt is analyzed with a shear DTA instrument. The melt state responsible for the saturation of shear-induced isothermal crystallization was identified previously as the steady state in steady shear flows and the strain applied to the melt was identified as the controlling factor for that saturation. Here it is shown that the same strain that saturates the isothermal crystallization also saturates the shear-induced nonisothermal crystallization. Regardless of the cooling rate, the nonisothermal crystallization, starting from the same sheared melt temperature, saturates at the same strain. The contribution of the melt memory effect to the overall nucleation density is estimated, and it is concluded that the majority of nuclei results from the thermal-induced crystallization.

Orientations of recrystallization nuclei developed in columnar-grained Ni at triple junctions and a high-angle grain boundary

A directionally solidified, high-purity nickel sample with a strong 〈0 0 1〉 fiber texture was cold rolled to 40% reduction. Electron backscattered diffraction (EBSD) was used to identify triple junctions (grain edges) before annealing the sample at 430 °C, after which further EBSD was performed to identify 17 recrystallization nuclei at the initially characterized triple junctions on the rolling plane. In addition, a longitudinal section was cut on which a further seven recrystallization nuclei were found and characterized. This characterization of all nuclei revealed that the majority of nuclei could be broadly associated with a 40° 〈1 1 1〉 misorientation to the matrix in which they formed, while a much lower percentage were found to have orientations as those of the local deformation substructure. However, a substantial fraction (around one-third) could not be associated with either of these types. Mechanisms for the formation of nuclei with new orientations are discussed, as is evidence of reorientation of material ahead of the recrystallization front.

Integrative Genomic Approaches Identify IKBKE as a Breast Cancer Oncogene

The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKepsilon), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKKepsilon expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKKepsilon activates the nuclear factor-kappaB (NF-kappaB) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF-kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery.