Showing papers by "Tohoku University published in 2002"

Sloan digital sky survey: Early data release

Abstract: The Sloan Digital Sky Survey (SDSS) is an imaging and spectroscopic survey that will eventually cover approximately one-quarter of the celestial sphere and collect spectra of ≈106 galaxies, 100,000 quasars, 30,000 stars, and 30,000 serendipity targets. In 2001 June, the SDSS released to the general astronomical community its early data release, roughly 462 deg2 of imaging data including almost 14 million detected objects and 54,008 follow-up spectra. The imaging data were collected in drift-scan mode in five bandpasses (u, g, r, i, and z); our 95% completeness limits for stars are 22.0, 22.2, 22.2, 21.3, and 20.5, respectively. The photometric calibration is reproducible to 5%, 3%, 3%, 3%, and 5%, respectively. The spectra are flux- and wavelength-calibrated, with 4096 pixels from 3800 to 9200 A at R ≈ 1800. We present the means by which these data are distributed to the astronomical community, descriptions of the hardware used to obtain the data, the software used for processing the data, the measured quantities for each observed object, and an overview of the properties of this data set.

The draft genome of Ciona intestinalis : insights into chordate and vertebrate origins

Abstract: The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.

The u'g'r'i'z' Standard-Star System

Abstract: We present the 158 standard stars that define the u'g'r'i'z' photometric system. These stars form the basis for the photometric calibration of the Sloan Digital Sky Survey. The defining instrument system and filters, the observing process, the reduction techniques, and the software used to create the stellar network are all described. We briefly discuss the history of the star selection process, the derivation of a set of transformation equations for the UBVRCIC system, and plans for future work.

Claudin-based tight junctions are crucial for the mammalian epidermal barrier a lesson from claudin-1–deficient mice

Abstract: The tight junction (TJ) and its adhesion molecules, claudins, are responsible for the barrier function of simple epithelia, but TJs have not been thought to play an important role in the barrier function of mammalian stratified epithelia, including the epidermis. Here we generated claudin-1–deficient mice and found that the animals died within 1 d of birth with wrinkled skin. Dehydration assay and transepidermal water loss measurements revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal. These unexpected findings prompted us to reexamine TJs in the epidermis of wild-type mice. Close inspection by immunofluorescence microscopy with an antioccludin monoclonal antibody, a TJ-specific marker, identified continuous TJs in the stratum granulosum, where claudin-1 and -4 were concentrated. The occurrence of TJs was also confirmed by ultrathin section EM. In claudin-1–deficient mice, claudin-1 appeared to have simply been removed from these TJs, leaving occludin-positive (and also claudin-4–positive) TJs. Interestingly, in the wild-type epidermis these occludin-positive TJs efficiently prevented the diffusion of subcutaneously injected tracer (∼600 D) toward the skin surface, whereas in the claudin-1–deficient epidermis the tracer appeared to pass through these TJs. These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.

An ordered mesoporous organosilica hybrid material with a crystal-like wall structure.

Abstract: Surfactant-mediated synthesis strategies are widely used to fabricate ordered mesoporous solids in the form of metal oxides, metals, carbon and hybrid organosilicas. These materials have amorphous pore walls, which could limit their practical utility. In the case of mesoporous metal oxides, efforts to crystallize the framework structure by thermal and hydrothermal treatments have resulted in crystallization of only a fraction of the pore walls. Here we report the surfactant-mediated synthesis of an ordered benzene-silica hybrid material; this material has an hexagonal array of mesopores with a lattice constant of 52.5 A, and crystal-like pore walls that exhibit structural periodicity with a spacing of 7.6 A along the channel direction. The periodic pore surface structure results from alternating hydrophilic and hydrophobic layers, composed of silica and benzene, respectively. We believe that this material is formed as a result of structure-directing interactions between the benzene-silica precursor molecules, and between the precursor molecules and the surfactants. We expect that other organosilicas and organo-metal oxides can be produced in a similar fashion, to yield a range of hierarchically ordered mesoporous solids with molecular-scale pore surface periodicity.

Japanese evaluated nuclear data library version 3 revision-3: JENDL-3.3

Abstract: The revision work of JENDL-3 has been made by considering feedback information of various benchmark tests. The main revised quantities are the resonance parameters, capture and inelastic scattering cross sections, and fission spectra of main actinide nuclides, the total and inelastic scattering cross sections of structural materials, the resonance parameters the capture and inelastic scattering cross sections of fission products, and the γ-ray production data. The revised data were released as JENDL-3.2 in June 1994. The preliminary benchmark tests indicate that JENDL-3.2 predicts various reactor characteristics more successfully than the previous version of JENDL-3.1.

Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study.

Abstract: Objective To examine the relationship between the normal nocturnal decline in blood pressure and the risk of cardiovascular mortality in individuals with and without high 24-h blood pressure values.Methods We obtained 24-h ambulatory blood pressure readings from 1542 residents of Ohasama, Japan, who

Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults

Abstract: Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults Eoin O’Brien,Thomas Pickering, Roland Asmar, Martin Myers, Gianfranco Parati, Jan Staessen, Thomas Mengden, Yutaka Imai, Bernard Waeber and Paolo Palatini and with the statistical assistance of Neil Atkins and William Gerin, on behalf of the Working Group on Blood Pressure Monitoring of the European Society of Hypertension

The XTH Family of Enzymes Involved in Xyloglucan Endotransglucosylation and Endohydrolysis: Current Perspectives and a New Unifying Nomenclature

Abstract: The polysaccharide xyloglucan is thought to play an important structural role in the primary cell wall of dicotyledons. Accordingly, there is considerable interest in understanding the biochemical basis and regulation of xyloglucan metabolism, and research over the last 16 years has identified a large family of cell wall proteins that specifically catalyze xyloglucan endohydrolysis and/or endotransglucosylation. However, a confusing and contradictory series of nomenclatures has emerged in the literature, of which xyloglucan endotransglycosylases (XETs) and endoxyloglucan transferases (EXGTs) are just two examples, to describe members of essentially the same class of genes/proteins. The completion of the first plant genome sequencing projects has revealed the full extent of this gene family and so this is an opportune time to resolve the many discrepancies in the database that include different names being assigned to the same gene. Following consultation with members of the scientific community involved in plant cell wall research, we propose a new unifying nomenclature that conveys an accurate description of the spectrum of biochemical activities that cumulative research has shown are catalyzed by these enzymes. Thus, a member of this class of genes/proteins will be referred to as a xyloglucan endotransglucosylase/hydrolase (XTH). The two known activities of XTH proteins are referred to enzymologically as xyloglucan endotransglucosylase (XET, which is hereby re-defined) activity and xyloglucan endohydrolase (XEH) activity. This review provides a summary of the biochemical and functional diversity of XTHs, including an overview of the structure and organization of the Arabidopsis XTH gene family, and highlights the potentially important roles that XTHs appear to play in numerous examples of plant growth and development.

Oral care reduces pneumonia in older patients in nursing homes.

Abstract: OBJECTIVES: Aspiration of oral secretions and their bacteria is increasingly being recognized as an important factor in pneumonia. We investigated whether oral care lowers the frequency of pneumonia in institutionalized older people. DESIGN: Survey. SETTING: Eleven nursing homes in Japan. PARTICIPANTS: Four hundred seventeen patients randomly assigned to an oral care group or a no oral care group. INTERVENTION: Nurses or caregivers cleaned the patients’ teeth by toothbrush after each meal. Swabbing with povidone iodine was additionally used in some cases. Dentists or dental hygienists provided professional care once a week. MEASUREMENTS: Pneumonia, febrile days, death from pneumonia, activities of daily living, and cognitive functions. RESULTS: During follow-up, pneumonia, febrile days, and death from pneumonia decreased significantly in patients with oral care. Oral care was beneficial in edentate and dentate patients. Activities of daily living and cognitive functions showed a tendency to improve with oral care. CONCLUSION: We suggest that oral care may be useful in preventing pneumonia in older patients in nursing homes. J Am Geriatr Soc 50:430‐433, 2002.

Roles of Fc receptors in autoimmunity.

Abstract: The receptors for the Fc of immunoglobulins, Fc receptors (FcRs), link the humoral and cellular branches of the immune system, and they have important functions in the activation and down-modulation of immune responses. Balanced signalling through activating and inhibitory FcRs regulates the activity of various cells in the immune system. Recent work in animal models indicates that the development of many human autoimmune diseases might be caused by impairment of the FcR regulatory system. This review provides an overview of the mechanisms of FcR-based immune regulation and describes how autoimmune disease might result from its dysfunction.

Hemoprotein Bach1 regulates enhancer availability of heme oxygenase‐1 gene

Abstract: Heme oxygenase-1 (HO-1) protects cells from various insults including oxidative stress. Transcriptional activators, including the Nrf2/Maf heterodimer, have been the focus of studies on the inducible expression of ho-1. Here we show that a heme-binding factor, Bach1, is a critical physiological repressor of ho-1. Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo, while heme abrogated this repressor function of Bach1 by inhibiting its binding to the ho-1 enhancers. Gene targeting experiments in mice revealed that, in the absence of Bach1, ho-1 became expressed constitutively at high levels in various tissues under normal physiological conditions. By analyzing bach1/nrf2 compound-deficient mice, we documented antagonistic activities of Bach1 and Nrf2 in several tissues. Chromatin immunoprecipitation revealed that small Maf proteins participate in both repression and activation of ho-1. Thus, regulation of ho-1 involves a direct sensing of heme levels by Bach1 (by analogy to lac repressor sensitivity to lactose), generating a simple feedback loop whereby the substrate effects repressor–activator antagonism.

The effect of filler loading and morphology on the mechanical properties of contemporary composites

Abstract: Statement of Problem Little information exists regarding the filler morphology and loading of composites with respect to their effects on selected mechanical properties and fracture toughness Purpose The objectives of this study were to: (1) classify commercial composites according to filler morphology, (2) evaluate the influence of filler morphology on filler loading, and (3) evaluate the effect of filler morphology and loading on the hardness, flexural strength, flexural modulus, and fracture toughness of contemporary composites Material and Methods Field emission scanning electron microscopy/energy dispersive spectroscopy was used to classify 3 specimens from each of 14 commercial composites into 4 groups according to filler morphology The specimens (each 5 × 25 × 15 mm) were derived from the fractured remnants after the fracture toughness test Filler weight content was determined by the standard ash method, and the volume content was calculated using the weight percentage and density of the filler and matrix components Microhardness was measured with a Vickers hardness tester, and flexural strength and modulus were measured with a universal testing machine A 3-point bending test (ASTM E-399) was used to determine the fracture toughness of each composite Data were compared with analysis of variance followed by Duncan's multiple range test, both at the P Results The composites were classified into 4 categories according to filler morphology: prepolymerized, irregular-shaped, both prepolymerized and irregular-shaped, and round particles Filler loading was influenced by filler morphology Composites containing prepolymerized filler particles had the lowest filler content (25% to 51% of filler volume), whereas composites containing round particles had the highest filler content (59% to 60% of filler volume) The mechanical properties of the composites were related to their filler content Composites with the highest filler by volume exhibited the highest flexural strength (120 to 129 MPa), flexural modulus (12 to 15 GPa), and hardness (101 to 117 VHN) Fracture toughness was also affected by filler volume, but maximum toughness was found at a threshold level of approximately 55% filler volume Conclusion Within the limitations of this study, the commercial composites tested could be classified by their filler morphology This property influenced filler loading Both filler morphology and filler loading influenced flexural strength, flexural modulus, hardness, and fracture toughness (J Prosthet Dent 2002;87:642-9)

Anatomical, Physiological, and Pharmacological Characteristics of Histidine Decarboxylase Knock-Out Mice: Evidence for the Role of Brain Histamine in Behavioral and Sleep–Wake Control

Abstract: The hypothesis that histaminergic neurons are involved in brain arousal is supported by many studies However, the effects of the selective long-term abolition of histaminergic neurons on the sleep–wake cycle, indispensable in determining their functions, remain unknown We have compared brain histamine(HA)-immunoreactivity and the cortical-EEG and sleep–wake cycle under baseline conditions or after behavioral or pharmacological stimuli in wild-type (WT) and knock-out mice lacking the histidine decarboxylase gene (HDC−/−) HDC−/−mice showed an increase in paradoxical sleep, a decrease in cortical EEG power in θ-rhythm during waking (W), and a decreased EEG slow wave sleep/W power ratio Although no major difference was noted in the daily amount of spontaneous W, HDC−/−mice showed a deficit of W at lights-off and signs of somnolence, as demonstrated by a decreased sleep latencies after various behavioral stimuli, eg, WT-mice placed in a new environment remained highly awake for 2–3 hr, whereas HDC−/−mice fell asleep after a few minutes These effects are likely to be attributable to lack of HDC and thus of HA In WT mice, indeed, intraperitoneal injection of α-fluoromethylhistidine (HDC-inhibitor) caused a decrease in W, whereas injection of ciproxifan (HA-H3 receptor antagonist) elicited W Both injections had no effect in HDC−/−mice Moreover, PCR and immunohistochemistry confirmed the absence of the HDC gene and brain HA-immunoreactive neurons in the HDC−/−mice These data indicate that disruption of HA-synthesis causes permanent changes in the cortical-EEG and sleep–wake cycle and that, at moments when high vigilance is required (lights off, environmental change… ), mice lacking brain HA are unable to remain awake, a prerequisite condition for responding to behavioral and cognitive challenges We suggest that histaminergic neurons also play a key role in maintaining the brain in an awake state faced with behavioral challenges

Periodontal Ligament Cells Under Mechanical Stress Induce Osteoclastogenesis by Receptor Activator of Nuclear Factor κB Ligand Up-Regulation via Prostaglandin E2 Synthesis†

Abstract: Previously, we discovered that periodontal ligament (PDL) cells not only support osteoclastogenesis through cell-to-cell contact, but also inhibit the formation of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells by a producing soluble factor(s). Furthermore, PDL cells express both receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) messenger RNA (mRNA). Clinically, "ankylosed teeth," which lack periodontal ligament, cannot be moved with orthodontic tooth treatment. From this, we hypothesized that PDL cells under mechanical stress should play a pivotal role in osteoclast formation during orthodontic tooth movement. This study examined how mechanical stress affects the osteoclastogenesis-supporting activity of PDL cells. PDL cells were compressed continuously and then cocultured with peripheral blood mononuclear cells (PBMCs) for 4 weeks. PDL cells under mechanical stress up-regulated osteoclastogenesis from PBMCs. Furthermore, the expression of RANKL mRNA and protein in PDL cells increased with compressive force in parallel with the change in the number of osteoclasts. In addition, cyclo-oxygenase 2 (COX-2) mRNA expression was induced by compressive force, and indomethacin inhibited the RANKL up-regulation resulting from compressive force. PDL cells under compressive force exhibited significantly increased prostaglandin E2 (PGE2) production in comparison with control PDL cells. Exogenous PGE2 treatment increased RANKL mRNA expression in PDL cells. Interestingly, OPG expression remained constant throughout compressive force or PGE2 treatment. In conclusion, compressive force up-regulated RANKL expression in PDL cells. Furthermore, RANKL up-regulation in mechanically stressed PDL cells was dependent on PGE2.

Observation of B̄0 → D(*)0 pp̄

Abstract: The B meson decay modes B → Dpp and B → D*pp have been studied using 29.4 fb - 1 of data collected with the Belle detector at KEKB. The B 0 → D 0 pp and B 0 → D* 0 pp decays have been observed for the first time with branching fractions B(B 0 → D 0 pp) = (1.18 ′ 0.15 ′ 0.16) X 10 - 4 and B(B 0 → D* 0 pp) = (1.20 + 0 . 3 3 - 0 . 2 9 ′ 0.21) X 10 - 4 . No signal has been found for the B + → D + pp and B + → D* + pp decay modes, and the corresponding upper limits at 90% C.L. are presented.

Effect of spin diffusion on Gilbert damping for a very thin permalloy layer in Cu/permalloy/Cu/Pt films

Abstract: Ferromagnetic resonance (FMR) was measured for Cu/permalloy (Py) (20, 30, 40 \AA{})/Cu ${(d}_{\mathrm{Cu}})/\mathrm{Pt}$ (0, 50 \AA{}) films with various ${d}_{\mathrm{Cu}}$ to clarify the effect of spin diffusion driven by the precession of magnetization on Gilbert damping. The peak-to-peak linewidth $\ensuremath{\Delta}{H}_{\mathrm{pp}}$ of the FMR spectra for Cu/Py/Cu/Pt films was very large at ${d}_{\mathrm{Cu}}=0\mathrm{\AA{}},$ and decreased remarkably at ${d}_{\mathrm{Cu}}=30\mathrm{\AA{}}.$ Above ${d}_{\mathrm{Cu}}=30\mathrm{\AA{}},$ it decreased gradually with increasing ${d}_{\mathrm{Cu}}$ in the anomalously wide range of ${d}_{\mathrm{Cu}}.$ The out-of-plane angular dependence of the FMR of Cu/Py(30 \AA{})/Cu ${(d}_{\mathrm{Cu}})/\mathrm{Pt}$ (0, 50 \AA{}) films was measured and analyzed using a Landau-Lifshitz-Gilbert equation that took into account the local variation of the effective demagnetizing field. The Gilbert damping coefficient G obtained from the analysis for Cu/Py/Cu/Pt films was about twice as large as that for Cu/Py/Cu films even at ${d}_{\mathrm{Cu}}=100\mathrm{\AA{}}$ and decreased gradually as ${d}_{\mathrm{Cu}}$ increased. At ${d}_{\mathrm{Cu}}=2000--3000\mathrm{\AA{}},$ G for Cu/Py/Cu/Pt and Cu/Py/Cu films has the same value. We discussed the influence of spin diffusion driven by the precession of magnetization in FMR on G using a previously proposed model. The calculated G vs ${d}_{\mathrm{Cu}}$ fitted well to the experimental one, and the other features of the experimental results are well explained by the model.

Development of General-Purpose Particle and Heavy Ion Transport Monte Carlo Code

Abstract: The high-energy particle transport code NMTC/JAM, which has been developed at JAERI, was improved for the high-energy heavy ion transport calculation by incorporating the JQMD code, the SPAR code and the Shen formula. The new NMTC/JAM named PHITS (Particle and Heavy-Ion Transport code System) is the first general-purpose heavy ion transport Monte Carlo code over the incident energies from several MeV/nucleon to several GeV/nucleon.

The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults

Abstract: The tumour suppressor p53 is important in the cell decision to either arrest cell cycle progression or induce apoptosis in response to a variety of stimuli. p53 post-translational modifications and association with other proteins have been implicated in the regulation of its stability and transcriptional activities1,2. Here we report that, on DNA damage, p53 interacts with Pin1, a peptidyl-prolyl isomerase3, which regulates the function of many proteins involved in cell cycle control and apoptosis4,5,6. The interaction is strictly dependent on p53 phosphorylation, and requires Ser 33, Thr 81 and Ser 315. On binding, Pin1 generates conformational changes in p53, enhancing its transactivation activity. Stabilization of p53 is impaired in UV-treated Pin1-/- cells owing to its inability to efficiently dissociate from Mdm2. As a consequence, a reduced p53-dependent response was detected in Pin1-/- cells, and this correlates with a diminished transcriptional activation of some p53-regulated genes. Our results suggest that, following stress-induced phosphorylation, p53 needs to form a complex with Pin1 and to undergo a conformational change to fulfil its biological roles.

Parameters controlling microstructure and hardness during friction-stir welding of precipitation-hardenable aluminum alloy 6063

Abstract: The aluminum (Al) alloys 6063-T5 and T4 were friction-stir welded at different tool rotation speeds (R), and then distributions of the microstructure and hardness were examined in these welds. The maximum temperature of the welding thermal cycle rose with increasing R values. The recrystallized grain size of the weld increased exponentially with increasing maximum temperature. The relationship between the grain size and the maximum temperature satisfied the static grain-growth equation. In the as-welded condition, 6063-T5 Al was softened around the weld center, whereas 6063-T4 Al showed homogeneous hardness profiles. Different R values did not result in significant differences in the hardness profile in these welds, except for the width of the softened region in the weld of 6063-T5 Al. Postweld aging raised the hardness in most parts of the welds, but the increase in hardness was small in the stir zone produced at the lower R values. Transmission electron microscope (TEM) observations detected a similar distribution of the strengthening precipitates in the grain interiors and the presence of a precipitation-free zone (PFZ) adjacent to the grain boundaries in all the welds. Microstructural analyses suggested that the small increase in hardness in the stir zone produced at the lower R values was caused by an increase in the volume fraction of PFZs.

Chemical-order-dependent magnetic anisotropy and exchange stiffness constant of FePt (001) epitaxial films

Abstract: Anomalous Hall voltage was measured for FePt ${L1}_{0}$ films having very high magnetic anisotropy. The magnetic anisotropy ${K}_{1}$ and ${K}_{2}$ were determined with high accuracy by analyzing the magnetization curves obtained from the Hall voltage measurement. The saturation magnetization ${M}_{s}$ of the samples with different chemical-order parameter (S) exhibits a different temperature dependence, implying that the Curie temperature weakly depends on S. The first-order anisotropy ${K}_{1}$ gradually increases with S, while the second-order anisotropy ${K}_{2}$ remains almost constant of about $5\ifmmode\times\else\texttimes\fi{}{10}^{6}\mathrm{e}\mathrm{r}\mathrm{g}/\mathrm{c}\mathrm{c}.$ The temperature dependence of ${K}_{1}$ is correlated with S, that is, ${K}_{1}$ with a small S is more temperature dependent than that with a large S. These behaviors are quite similar to the temperature dependence of ${M}_{s}$ with different S, and can be explained by the conventional model based on thermal spin fluctuations. The domain wall energy ${\ensuremath{\sigma}}_{w}$ evaluated by the theoretical analysis of the stripe-domain structure tends to increase linearly with S, in a similar manner as that of ${K}_{1},$ whereas the exchange stiffness constant A of about $1\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}\mathrm{e}\mathrm{r}\mathrm{g}/\mathrm{c}\mathrm{m}$ deduced from ${\ensuremath{\sigma}}_{w}$ and ${K}_{u}{(=K}_{1}{+K}_{2})$ hardly depends on S.

The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response

Abstract: p53 is activated in response to various genotoxic stresses resulting in cell cycle arrest or apoptosis1,2. It is well documented that DNA damage leads to phosphorylation and activation of p53 (refs 1–3), yet how p53 is activated is still not fully understood. Here we report that DNA damage specifically induces p53 phosphorylation on Ser/Thr-Pro motifs, which facilitates its interaction with Pin1, a member of peptidyl-prolyl isomerase4,5,6,7,8,9. Furthermore, the interaction of Pin1 with p53 is dependent on the phosphorylation that is induced by DNA damage. Consequently, Pin1 stimulates the DNA-binding activity and transactivation function of p53. The Pin1-mediated p53 activation requires the WW domain, a phosphorylated Ser/Thr-Pro motif interaction module, and the isomerase activity of Pin1. Moreover, Pin1-deficient cells are defective in p53 activation and timely accumulation of p53 protein, and exhibit an impaired checkpoint control in response to DNA damage. Together, these data suggest a mechanism for p53 regulation in cellular response to genotoxic stress.