Towards a unified model of neutrino-nucleus reactions for neutrino oscillation experiments.

A precise description of neutrino-nucleus reactions will play a key role in addressing fundamental questions such as the leptonic CP violation and the neutrino mass hierarchy through analyzing data from next-generation neutrino oscillation experiments. The neutrino energy relevant to the neutrino-nucleus reactions spans a broad range and, accordingly, the dominant reaction mechanism varies across the energy region from quasi-elastic scattering through nucleon resonance excitations to deep inelastic scattering. This corresponds to transitions of the effective degree of freedom for theoretical description from nucleons through meson-baryon to quarks. The main purpose of this review is to report our recent efforts towards a unified description of the neutrino-nucleus reactions over the wide energy range; recent overall progress in the field is also sketched. Starting with an overview of the current status of neutrino-nucleus scattering experiments, we formulate the cross section to be commonly used for the reactions over all the energy regions. A description of the neutrino-nucleon reactions follows and, in particular, a dynamical coupled-channels model for meson productions in and beyond the [Formula: see text](1232) region is discussed in detail. We then discuss the neutrino-nucleus reactions, putting emphasis on our theoretical approaches. We start the discussion with electroweak processes in few-nucleon systems studied with the correlated Gaussian method. Then we describe quasi-elastic scattering with nuclear spectral functions, and meson productions with a [Formula: see text]-hole model. Nuclear modifications of the parton distribution functions determined through a global analysis are also discussed. Finally, we discuss issues to be addressed for future developments.

Ultrashort echo time imaging of normal middle ear ossicles: a feasibility study.

OBJECTIVE: The aim of this study was to assess the feasibility of ultrashort echo time (UTE) imaging in the visualization of middle ear ossicles in normal subjects. METHODS: 12 young adult volunteers (males/females = 6/6, age 25-44 years, mean 30.3 years) with normal hearing levels underwent MRI studies using a 3.0 T clinical unit with an eight-channel SENSE head coil. For each subject, the whole head was imaged using a three-dimensional dual-echo UTE imaging sequence with radial trajectory and the following parameters: field of view, 240 × 240 × 240 mm; matrix, 320 × 320; flip angle, 7°; repetition time/echo time (TE)1/TE2, 8.0 ms/0.14 ms/1.8 ms; acquisition voxel size, 0.75 × 0.75 × 0.75 mm; number of signals averaged, 1; imaging time, 27 min 20 s. Subsequently, subtraction images were obtained by subtracting long TE (1.8 ms) images from short TE (0.14 ms) images. By using these three images, the visibility of the bilateral middle ear ossicles was evaluated. Moreover, as a reference for the UTE findings, CT images of the temporal bone were obtained in one volunteer. RESULTS: In all subjects, the middle ear ossicles were clearly visualized as a high signal intensity spot surrounded by a signal void of air on short TE images bilaterally, while they were not visible in long TE images in any of the subjects. The subtraction images provided better contrast of the ossicles. CONCLUSION: We demonstrated the feasibility of UTE imaging of the middle ear ossicle in normal subjects.

Detection of middle ear cholesteatoma by diffusion-weighted MR imaging: multishot echo-planar imaging compared with single-shot echo-planar imaging.

BACKGROUND AND PURPOSE: Previous reports have shown that DWI is useful in detecting cholesteatoma. SS-EPI is the most widely used DWI technique. However, SS-EPI may have susceptibility artifacts due to field inhomogeneity in the imaging of the temporal bone region. Our purpose was to prospectively evaluate the advantage of MS-EPI for the diagnosis of middle ear cholesteatoma by comparing it with SS-EPI. MATERIALS AND METHODS: We studied 29 patients with preoperatively suspected acquired cholesteatoma. Each patient underwent an MR imaging examination including both SS-EPI and MS-EPI by using a 1.5T MR imaging scanner. Images of the 29 patients (58 temporal bones including 30 with and 28 without cholesteatoma) were reviewed by 2 independent neuroradiologists. The confidence level for the presence of cholesteatoma was graded on a scale of 0-2 (0 = none, 1 = equivocal, 2 = definite). Interobserver agreement as well as sensitivity, specificity, and accuracy were assessed for the 2 readers. RESULTS: Excellent interobserver agreement was shown for both MS-EPI (κ = 0.856) and SS-EPI (κ = 0.820). MS-EPI was associated with higher sensitivity (76.7%) and accuracy (87.9%) than SS-EPI (sensitivity = 50.0%, accuracy = 74.1%) (P < .05), while both methods showed 100% specificity. CONCLUSIONS: Compared with SS-EPI, MS-EPI improves the accuracy of the diagnosis of acquired middle ear cholesteatomas.

3D turbo spin-echo sequence with motion-sensitized driven-equilibrium preparation for detection of brain metastases on 3T MR imaging.

BACKGROUND AND PURPOSE: MSDE preparation is a technique for black-blood imaging. Our purpose was to evaluate the usefulness of a 3D TSE sequence with MSDE preparation in detecting brain metastases by comparing it with conventional sequences. MATERIALS AND METHODS: Postcontrast images of 227 patients who were suspected of having brain metastasis were prospectively obtained by using 3 T1-weighted 3D sequences: a gradient-echo sequence (MPRAGE), TSE-noMSDE, and TSE-MSDE. The number of visualized blood vessels and the lesion-to-normal CNR were compared among the 3 sequences. An observer test involving 9 radiologists was performed, and their diagnostic performance by using TSE-MSDE, MPRAGE, and combined TSE-MSDE and MPRAGE was compared by means of an FOM as an index of diagnostic performance derived by the JAFROC analysis, sensitivity, FP/case, and reading time. RESULTS: TSE-MSDE resulted in significantly better vessel suppression than the other 2 methods. TSE with and without MSDE resulted in significantly higher CNRs than MPRAGE. In the observer test, significantly higher sensitivity and FOM as well as significantly shorter reading time were achieved by TSE-MSDE compared with MPRAGE, but FP/case was significantly higher with TSE-MSDE. Combined TSE-MSDE/MPRAGE resulted in significantly higher sensitivity and FOM and similar FP/case and reading time compared with MPRAGE alone. CONCLUSIONS: With blood vessel suppression and increased CNR, TSE-MSDE improves radiologists' performances in detecting brain metastases compared with MPRAGE, but it may increase FP results. Combined with MPRAGE, TSE-MSDE achieves high diagnostic performance while maintaining a low FP rate.

Disentangling the dynamical origin of P11 nucleon resonances.

We show that two almost degenerate poles near the piDelta threshold and the next higher mass pole in the P11 partial wave of piN scattering evolve from a single bare state through its coupling with piN, etaN, and pipiN reaction channels. This finding provides new information on understanding the dynamical origins of the Roper N{*}(1440) and N{*}(1710) resonances listed by Particle Data Group. Our results for the resonance poles in other piN partial waves are also presented.

Diagnosis of Alzheimer's Disease: Two MRI-Based Approaches.

Imaging has been increasingly recognized as a powerful tool for diagnosing Alzheimer's disease (AD). Magnetic resonance imaging (MRI) is advantageous over other imaging modalities due to its non-invasiveness and multi-parametric capabilities. In addition to the morphological assessment, several new MR imaging approaches have shown potential for improved AD diagnosis. This paper focuses on two of these advanced MRI-based approaches: diffusion-weighted imaging and arterial spin labeling.

Subsequent fracture after percutaneous vertebroplasty can be predicted on preoperative multidetector row CT.

BACKGROUND AND PURPOSE: Subsequent fracture is often seen after percutaneous vertebroplasty. The purpose of this prospective study was to evaluate preoperative multidetector row CT (MDCT) for the prediction of subsequent fractures after vertebroplasty. MATERIALS AND METHODS: This study included 26 consecutive patients (18 women and 8 men) with osteoporotic compression fractures (58 vertebrae). A 64-section MDCT with multiplanar reformation was obtained 1 day before the procedure. Subsequent MR imaging was used to evaluate new fractures at least 3 months after treatment on a routine basis or if there was recurrent pain. We used logistic regression analysis with MDCT findings and clinical data for statistical evaluation according to the location of new fractures. RESULTS: Subsequent fractures were noted at 14 adjacent vertebrae (12.1%) in 13 patients and at 14 remote vertebrae in 6 patients (23.1%). Subsequent fractures in adjacent vertebrae tended to occur in small vertebrae before treatment (P < .05). Steroid medication and low CT value in nonfractured vertebrae were associated with subsequent fractures in remote vertebrae (P < .05). Further collapse of the treated vertebral bodies was noted in 10 patients (11 vertebrae [19.0%]) without specific findings (P > .05). CONCLUSIONS: The small size of the treated vertebrae may relate to subsequent fractures in adjacent vertebrae. Steroid use and low CT value of nonfractured vertebrae on preoperative MDCT can be associated with subsequent fractures in remote vertebrae.

Simultaneous measurement of arterial transit time, arterial blood volume, and cerebral blood flow using arterial spin-labeling in patients with Alzheimer disease.

BACKGROUND AND PURPOSE: Cerebral hemodynamics abnormality in Alzheimer disease (AD) is not fully understood. Our aim was to determine whether regional hypoperfusion due to AD is associated with abnormalities in regional arterial blood volume (rABV) and regional arterial transit time (rATT) as measured by quantitative arterial spin-labeling (ASL) with multiple-delay time sampling. MATERIALS AND METHODS: Nineteen patients with AD (9 men and 10 women; mean age, 74.5 +/- 8.6 years) and 22 cognitively healthy control subjects (11 men and 11 women; mean age, 72.8 +/- 6.8 years) were studied by using a quantitative ASL method with multiple-delay time sampling. From the ASL data, maps of regional cerebral blood flow (rCBF), rABV, and rATT were generated. A region of hypoperfusion due to AD was determined by statistical parametric mapping (SPM) analysis. Mean rCBF, rABV, and rATT values within the hypoperfused region were compared between the AD and control groups. RESULTS: Despite the significantly lower rCBF (P = .0004) in patients with AD (27.8 +/- 7.1 mL/100 g/min) in comparison with control subjects (36.7 +/- 6.3 mL/100 g/min), no significant difference in rATT was observed between the control (0.48 +/- 0.09 seconds) and AD (0.47 +/- 0.10 seconds) groups. Mean rABV was lower in the AD group (0.22 +/- 0.10%) than in the control group (0.27 +/- 0.12%), though the difference did not reach the level of statistical significance. CONCLUSIONS: Our results revealed that regional hypoperfusion in AD is not associated with rATT prolongation, suggesting that the mechanism of hypoperfusion is distinct from that in cerebrovascular diseases.

Kyphoplasty and vertebroplasty produce the same degree of height restoration.

BACKGROUND AND PURPOSE: There are few comparative studies regarding morphologic changes after kyphoplasty and vertebroplasty. The purpose of this study was to compare restoration of vertebral body height and wedge angle and cement leakage with kyphoplasty and vertebroplasty in osteoporotic compression fractures. MATERIALS AND METHODS: Forty patients (57 vertebrae) were treated with kyphoplasty, and 66 patients (124 vertebrae) were treated with vertebroplasty. Cement leakage into the disk space and paravertebral soft tissues or veins was analyzed on immediate postoperative CT scans. The height and wedge angle were measured before and after treatment and analyzed with the Mann-Whitney U test and chi(2) test. RESULTS: Kyphoplasty and vertebroplasty both improved vertebral body height and the wedge angles (P < .05). However, these differences were not statistically significant when the 2 techniques were compared (P > .05). There were 18% of the kyphoplasty group and 49% of the vertebroplasty group that showed cement leakage into the paravertebral soft tissues or veins (P < .01). Cement leakage into the disk space occurred in 12% of the kyphoplasty group and in 25% of the vertebroplasty group (P < .01). However, no complications related to cement leakage were noted. CONCLUSIONS: Both kyphoplasty and vertebroplasty achieved the same degree of height restoration and improvement of the wedge angle. Kyphoplasty resulted in less cement leakage into the disk space and paravertebral soft tissues or veins than vertebroplasty.

Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukemia for thrombopoietin-induced aggregation.

In this study, we examined the effect of thrombopoietin (TPO) on the aggregation of platelets from 40 patients with myeloproliferative disorders (MPDs), including 17 patients with chronic myelogenous leukemia in the chronic phase (CML-CP), 10 with polycythemia vera, 10 with essential thrombocythemia, and three with myelofibrosis. TPO by itself dose-dependently induced the aggregation of platelets from patients with CML-CP but not from those with other MPDs or with CML-CP in cytogenetical complete remission. The expression of CD63 in CML-CP platelets was induced by TPO treatment. Phosphatidylinositol 3-kinase (PI3-kinase) was constitutively activated in CML-CP platelets. Pretreatment with PI3-kinase inhibitors (wortmannin and LY294002) dose-dependently inhibited TPO-induced aggregation of CML-CP platelets. The Abl kinase inhibitor imatinib mesylate and the Jak inhibitor AG490 suppressed TPO-induced aggregation of CML-CP platelets. Pretreatment with imatinib mesylate, but not with AG490, inhibited the activity of PI3-kinase in CML-CP platelets. In addition, tyrosine phosphorylation of Jak2 was undetected in CML-CP platelets before TPO treatment. These findings indicate that the constitutive activation of PI3-kinase primes CML-CP platelets for the aggregation induced by TPO, and that Bcr-Abl, but not Jak family protein tyrosine kinases, are involved in the constitutive activation of PI3-kinase in CML-CP platelets.

Src directly tyrosine-phosphorylates STAT5 on its activation site and is involved in erythropoietin-induced signaling pathway.

Signal transducers and activators of transcription (STAT) proteins are transcription factors activated by phosphorylation on tyrosine residues after cytokine stimulation. In erythropoietin receptor (EPOR)-mediated signaling, STAT5 is tyrosine-phosphorylated by EPO stimulation. Although Janus Kinase 2 (JAK2) is reported to play a crucial role in EPO-induced activation of STAT5, it is unclear whether JAK2 alone can tyrosine-phosphorylate STAT5 after EPO stimulation. Several studies indicate that STAT activation is caused by members of other families of protein tyrosine kinases such as the Src family. We previously reported that reduction of Src by induction of antisense src RNA expression suppressed EPO-promoted erythroid differentiation in K562 cells. In the present study, we explored the function of Src downstream of the EPOR-initiated signaling. Reduction of Src diminished tyrosine phosphorylation of STAT5 in K562 cells regardless of EPO treatment. The tyrosine phosphorylation level of STAT5 induced by EPO in F-36P cells was reduced in the presence of PP1 or PP2 selective Src inhibitor. In addition, the expression of dominant negative Src in F-36P cells reduced the tyrosine phosphorylation of STAT5. When Src and STAT5 were co-expressed in COS7 cells, tyrosine phosphorylation of STAT5 was observed, and tyrosine residue 694 (Tyr 694) of STAT5A was identified as the major phosphorylation site by Src. In vitro kinase assay revealed that GST-STAT5 fusion protein with the conserved C-terminal, but not the C-terminal-truncated mutant which lacks Tyr 694, was tyrosine-phosphorylated by Src. Src can thus directly tyrosine-phosphorylate the activation site of STAT5 (Tyr 694 in STAT5A), and Src may contribute to EPO-induced signal transduction via STAT5.

Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase.

In this study, we examined the molecular mechanism of erythropoietin-initiated signal transduction of erythroid differentiation through Src and phosphatidylinositol 3-kinase (PI3-kinase). Antisense oligonucleotides against src but not lyn inhibited the formation of erythropoietin-dependent colonies derived from human bone marrow cells and erythropoietin-induced differentiation of K562 human erythroleukaemia cells. Antisense p85alpha oligonucleotide or LY294002, a selective inhibitor of PI3-kinase, independently inhibited the formation of erythropoietin-dependent colonies. In K562 cells, Src associated with PI3-kinase in response to erythropoietin. Antisense src RNA expression in K562 cells inhibited the erythropoietin-induced activation of PI3-kinase and its association with erythropoietin receptor. PP1, a selective inhibitor of the Src family, reduced erythropoietin-induced tyrosine phosphorylation of erythropoietin receptor and its association with PI3-kinase in F-36P human erythroleukaemia cells. The coexpression experiments and in vitro kinase assay further demonstrated that Src directly tyrosine-phosphorylated erythropoietin receptor, and associated with PI3-kinase. In vitro binding experiments proved that glutathione S-transferase-p85alpha N- or C-terminal SH2 domains independently bound to erythropoietin receptor, which was tyrosine-phosphorylated by Src. Taken together, Src transduces the erythropoietin-induced erythroid differentiation signals by regulating PI3-kinase activity.

Antisense src expression inhibits tyrosine phosphorylation of Shc and its association with Grb2 and Sos which leads to MAP kinase activation in U937 human leukemia cells.

We constructed a recombinant plasmid which expresses antisense src RNA after dexamethasone (Dexa) treatment, and transfected it into U937 human monoblastic leukemia cells (U937-ASRC). Induction of antisense src RNA expression diminished the amounts of c-Src and its protein tyrosine kinase (PTK) activity in U937-ASRC cells. The declines in c-Src and its PTK activity subsequently reduced the proliferation of U937-ASRC cells. To elucidate the growth signal transduction pathway downstream of c-Src, tyrosine phosphorylation of Shc was examined in U937-ASRC cells treated with Dexa. The decline in c-Src by induction of antisense src RNA expression decreased the level of tyrosine phosphorylation of Shc. Immunoprecipitated c-Src directly phosphorylated immunoprecipitated Shc on tyrosine residues in vitro. The amounts of Grb2 and Sos co-immunoprecipitated with Shc were decreased after Dexa treatment. However, the amount of Sos co-immunoprecipitated with Grb2 was apparently not affected by Dexa treatment. These results indicate that Grb2 and Sos constitutively associate with each other in U937 cells. Furthermore, the level of phosphorylation on tyrosine (204) essential for MAP kinase activation was decreased after Dexa treatment. Taken together with all these findings, it is suggested that c-Src directly phosphorylates Shc on tyrosine residues, which in turn binds to Grb2 constitutively associated with Sos to form a Shc-Grb2-Sos complex, and that the complex formation is coupled with MAP kinase activation mediated by Ras activation in U937 cells.

B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter.

Previous studies have shown that B-Myb, a conserved member of the Myb transcription factor family, is a potent activator of the promoter of the human HSP70 gene but does not activate promoters containing Myb binding sites. We have now investigated the transactivation properties of B-Myb in more detail. We here report that B-Myb activates the HSP70 promoter by a novel mechanism which involves the heat shock element (HSE). Deletion analysis of B-Myb shows that a specific domain in the center of B-Myb, but not the DNA-binding domain is required for HSE-dependent transactivation. We also show that deletion of the C-terminal domain of B-Myb does not affect HSE-dependent transactivation but allows the protein to activate a promoter containing Myb binding sites. This suggests that the ability to activate Myb binding site containing promoters is repressed in the context of full length B-Myb and that HSE dependent and Myb binding site dependent transactivation are distinct functions of B-Myb. Finally, we report that cyclin D1 like B-Myb strongly activates the HSP70 promoter via the HSE. HSE-dependent transactivation is a novel activity of cyclin D1 and appears to be independent of the phosphorylation of the Rb protein. Our results reveal an interesting and unexpected connection between HSE-dependent gene activation and proteins expressed during the G1/S-transition of the cell cycle.

Expression of B-Myb during mouse embryogenesis.

B-myb is a member of the myb family of nuclear sequence-specific DNA-binding proteins which has been highly conserved among vertebrates. B-myb has been implicated in the control of cell proliferation, particularly at the G1/S transition of the cell cycle. So far, most of the work on B-myb has been performed in immortalized cell lines. Since these cells might show aberrant behavior of genes involved in proliferation control we have begun to investigate the role of B-myb in normal cells. As a first step, we have studied the expression of B-myb during mouse development. Here, we show the B-myb is expressed at similar levels during all stages of embryogenesis. In situ hybridization reveals a tight linkage between B-myb expression and proliferative activity (as assessed by the expression of the S-phase specific histone H4 gene) in most tissues and throughout embryonic development. However, B-myb and histone H4 expression are uncoupled during spermatogenesis in the adult mouse. Histone H4 is expressed at high levels in the early spermatogenic progenitor cells but not in successive stages of sperm cell development. By contrast, the highest levels of B-myb expression are found during the intermediate stages of spermatogenesis. Furthermore, we have found that B-myb mRNA isolated from the testis differs in size from that of other tissues. The data presented here strongly support the notion that B-myb plays a general role during proliferation of most cells. Furthermore, our results raise the possibility that the function of B-myb in cells undergoing meiosis may be different from its role in cells dividing mitotically.

Differential splicing of the mouse B-myb gene.

The myb gene family consists of three members, the c-myb proto-oncogene and two myb-related genes (A-myb and B-myb), all of which encode nuclear DNA-binding proteins. Unlike c-myb, which plays a critical role in hematopoietic cells, B-myb is expressed in a large spectrum of hematopoietic as well as non-hematopoietic cells and has been implicated in the control of cell proliferation. The isolation of B-myb cDNA clones from several species has shown that B-myb shares limited homology to the so-called exon 9A of the c-myb gene. This exon is involved in differential splicing as only a subfraction of c-myb mRNA contains exon 9A sequences. The presence in the B-myb cDNA of a sequence related to the exon 9A of c-myb has prompted us to investigate whether B-myb mRNA is also spliced differentially. We here show that B-myb mRNAs containing or lacking exon 9A related sequences are present in many cell types. In contrast to c-myb, where RNA containing the exon 9A constitutes only a minor mRNA fraction, B-myb RNA containing the exon 9A related sequences is the major mRNA form. The proteins encoded by the two B-myb mRNA species are unable to activate promoters to which they bind. Curiously, both B-myb proteins differ in their ability to activate the HSP70 promoter by a myb binding-site independent mechanism; B-myb protein containing exon 9A related aminoacid sequences activates the HSP70 promoter much more potently than the B-myb protein which lacks these sequences. Our results suggest that differential splicing may be a general feature of the members of the myb family and provide first evidence for functional differences of the splice variants.

Effects of the antisense myb expression on hemin- and erythropoietin-induced erythroid differentiation of K562 cells.

In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin (Hm) and erythropoietin (Epo), we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone. During treatment with Hm, K562 cells constitutively expressed c-myb mRNA, and 50% of them began to synthesize hemoglobin (Hb). Expression of antisense myb RNA reduced the amount of c-myb mRNA, and the percentage of Hb-synthesizing cells was decreased to 20%. In the presence of Epo, c-myb mRNA declined and 20% of K562 cells synthesized Hb regardless of antisense myb RNA expression. It is suggested that constitutive expression of c-myb mRNA is necessary for Hm-induced differentiation, and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm-induced differentiation. The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo. Expression of GATA-1 mRNA was almost constant during Hm-induced differentiation, but increased during Epo treatment. It is supposed that the mechanism of Hm-induced differentiation is distinguished from that of Epo-induced differentiation in K562 cells.