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Diamond-Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome that is associated with anemia, congenital anomalies, and cancer predisposition. It is categorized as a ribosomopathy, because more than 80% or patients have haploinsufficiency of either a small or large subunit-associated ribosomal protein (RP). The erythroid pathology is due predominantly to a block and delay in early committed erythropoiesis with reduced megakaryocyte/erythroid progenitors (MEPs). To understand the molecular pathways leading to pathogenesis of DBA, we performed RNA sequencing on mRNA and miRNA from RPS19-deficient human hematopoietic stem and progenitor cells (HSPCs) and compared existing database documenting transcript fluctuations across stages of early normal erythropoiesis. We determined the chromatin regulator, SATB1 was prematurely downregulated through the coordinated action of upregulated miR-34 and miR-30 during differentiation in ribosomal insufficiency. Restoration of SATB1 rescued MEP expansion, leading to a modest improvement in erythroid and megakaryocyte expansion in RPS19 insufficiency. However, SATB1 expression did not affect expansion of committed erythroid progenitors, indicating ribosomal insufficiency affects multiple stages during erythroid differentiation.

Disruption of cyclic adenosine monophosphate response element binding protein (CREB) provides a potential new strategy to address acute leukemia, a disease associated with poor prognosis, and for which conventional treatment options often carry a significant risk of morbidity and mortality. We describe the structure-activity relationships (SAR) for a series of XX-650-23 derived from naphthol AS-E phosphate that disrupts binding and activation of CREB by the CREB-binding protein (CBP). Through the development of this series, we identified several salicylamides that are potent inhibitors of acute leukemia cell viability through inhibition of CREB-CBP interaction. Among them, a biphenyl salicylamide, compound 71, was identified as a potent inhibitor of CREB-CBP interaction with improved physicochemical properties relative to previously described derivatives of naphthol AS-E phosphate.

Nemo-like kinase (NLK) is a member of the mitogen-activated protein kinase family of kinases and shares a highly conserved kinase domain with other mitogen-activated protein kinase family members. The activation of NLK contributes to the pathogenesis of Diamond–Blackfan anemia (DBA), reducing c-myb expression and mechanistic target of rapamycin activity, and is therefore a potential therapeutic target. Unlike other anemias, the hematopoietic effects of DBA are largely restricted to the erythroid lineage. Mutations in ribosomal genes induce ribosomal insufficiency and reduced protein translation, dramatically impacting early erythropoiesis in the bone marrow of patients with DBA. We sought to identify compounds that suppress NLK and increases erythropoiesis in ribosomal insufficiency. We report that the active component of ginseng, ginsenoside Rb1, suppresses NLK expression and improves erythropoiesis in in vitro models of DBA. Ginsenoside Rb1–mediated suppression of NLK occurs through the upregulation of miR-208, which binds to the 3′-UTR of NLK mRNA and targets it for degradation. We also compare ginsenoside Rb1–mediated upregulation of miR-208 with metformin-mediated upregulation of miR-26. We conclude that targeting NLK expression through miRNA binding of the unique 3′-UTR is a viable alternative to the challenges of developing small-molecule inhibitors to target the highly conserved kinase domain of this specific kinase.

CREB binding protein (CBP) and p300 are critical regulators of hematopoiesis through both their transcriptional coactivator and acetyltransferase activities. Loss or mutation of CBP/p300 results in hematologic deficiencies in proliferation and differentiation as well as disruption of hematopoietic stem cell renewal and the microenvironment. Aberrant lysine acetylation mediated by CBP/p300 has recently been implicated in the genesis of multiple hematologic cancers. Understanding the effects of disrupting the acetyltransferase activity of CBP/p300 could pave the way for new therapeutic approaches to treat patients with these diseases.

5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype.

Diamond Blackfan Anemia (DBA) is associated with anemia, congenital abnormalities, and cancer. Current therapies for DBA have undesirable side effects, including iron overload from repeated transfusions or infections from immunosuppressive drugs and stem cell transplantation. Nemo-like Kinase (NLK) is hyperactivated in erythroid progenitors in murine and human models as well as DBA patients. In an RPS19-insufficient human model, genetic silencing of NLK increased erythroid expansion by 2.2 fold, indicating that aberrant NLK activation contributes to disease pathogenesis. A high-throughput inhibitor screen identified a compound that inhibits NLK (IC50:440nM) and increased erythroid expansion in murine (5.4 fold) and human (6.3 fold) models of DBA with no effect on wild type erythropoiesis (EC50: 0.7 µM). Virtually identical results were observed in CD34+ progenitors from 3 DBA patient bone marrow aspirates with 2.3, 1.9 and 2.1 fold increases in CD235+ erythroblast generation. In erythroid progenitors, RPS19 insufficiency increased phosphorylation of the mTORC1 component Raptor, reducing mTOR activity by 82%. This was restored to basal levels upon inhibition of NLK. To compensate for a reduction in ribosomes, stimulating mTOR activity with leucine has been proposed to increase translational efficiency in DBA patients. Probably due to NLK phosphorylation of raptor, DBA patients did not respond as anticipated. While leucine treatment mildly increased mTOR activity in both control and RPS19-insufficiency, combining leucine with NLK inhibition increased mTOR activity to 142% of control and significantly improved erythroid expansion. Identification of aberrantly activated enzymes, such as NLK, offer therapeutic promise used alone, or in combination with existing therapies, as druggable targets in the clinical management of DBA.

Myelodysplastic syndromes (MDS) are characterized by cytopenias resulting from ineffective hematopoiesis with a predisposition to transform to acute myeloid leukemia (AML). Recent evidence suggests that the hematopoietic stem cell microenvironment contributes to the pathogenesis of MDS. Inflammation and hypoxia within the bone marrow are key regulators of hematopoietic stem and progenitor cells that can lead to several bone marrow failure syndromes, including MDS. In this brief review, we provide an overview of the clinical and molecular features of MDS, the bone marrow microenvironment, and specific pathways that lead to abnormal blood cell development in MDS. Characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease.

Ulnar neuropathy about the elbow has been described and debated for years, though there is no consensus on the best surgical treatment. Current meta-analyses show equivalent outcomes after in situ decompression and anterior transposition. Recent trends have been toward in situ decompression through limited incisions or with endoscopic techniques. Further research is needed to determine the strength of prognostic factors, such as duration of symptoms and preoperative severity of disease, which may change our threshold for surgical intervention. The ulnar nerve should also be addressed in cases of distal humerus fracture, generally with in situ decompression, as transposition does not appear to decrease rates of ulnar neuropathy. In elbow contractures, prophylactic ulnar nerve decompression should be liberally used, especially in cases of heterotopic ossification, scarring about the nerve, and preexisting symptoms, to prevent postoperative and delayed-onset ulnar neuropathy.

Deuterium trapping by defects in W polycrystalline foils during ion bombardment was investigated by thermal desorption spectroscopy using the low fluence probe method. Probe TDS spectra showed, that there are at least six peaks in the region 350–900 K: at 370 K, 450 K, 530 K, 580 K, 630 K, 750 K. Experiments with as received samples showed that D is trapped mainly in low energy traps in the region 390–650 K. These defects are attributed to technological defects such as dislocations and vacancies. The peak at 750 K easily disappears when annealing the sample at about 1300 K and can be attributed to vacancy clusters. The peak at 630 K irreversibly increases at high fluence, it also appears when annealing the sample above 1300 K. This peak can be attributed to voids. Voids of about 20 nm in diameter in the near surface region were observed by FIB/SEM in cases when 630 K peak was observed.

Diamond Blackfan anemia (DBA) is a congenital bone marrow (BM) failure syndrome that typically results in macrocytic anemia within the first year of life. DBA is also associated with birth defects, increased incidence of cancer, and other cytopenias. Shwachman-Diamond syndrome (SDS) is a multisystem disease characterized by exocrine pancreatic dysfunction, impaired hematopoiesis, and leukemia predisposition. Other clinical features include skeletal, immunologic, hepatic, and cardiac disorders. Treatment for these BM failure syndromes, including stem cell transplantation (SCT), will be discussed in this review.

The p53 family network is a unique cellular processor that integrates information from various pathways and determines cellular choices between proliferation, replication arrest/repair, differentiation, senescence, or apoptosis. The most studied role of the p53 family is the regulation of stress response and tumor suppression. By removing damaged cells from the proliferating pool, p53 family members preserve the integrity of the genome. In addition to this well recognized role, recent data implicate the p53 protein family in a broader role of controlling cell proliferation, differentiation and death. Members of the p53 protein family with opposing activity perform coordination of these processes. Imbalance of p53 protein family may contribute to a significant proportion of congenital developmental abnormalities in humans.

Purpose Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term "oligometastasis" is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors. Methods and Materials A total of 34 patients with oligometastatic lung tumors were included in this study. The primary involved organs were the lung ( n = 15), colorectum ( n = 9), head and neck ( n = 5), kidney ( n = 3), breast ( n = 1), and bone ( n = 1). Five to seven, noncoplanar, static 6-MV photon beams were used to deliver 48 Gy ( n = 18) or 60 Gy ( n = 16) at the isocenter, with 12 Gy/fraction within 4–18 days (median, 12 days). Results The overall survival rate, local relapse-free rate, and progression-free rate at 2 years was 84.3%, 90.0%, and 34.8%, respectively. No local progression was observed in tumors irradiated with 60 Gy. SBRT-related pulmonary toxicities were observed in 4 (12%) Grade 2 cases and 1 (3%) Grade 3 case. Patients with a longer disease-free interval had a greater overall survival rate. Conclusion The clinical result of SBRT for oligometastatic lung tumors in our institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastases.

Misfolded or unfolded proteins are often refolded with the help of chaperones or degraded by the 26S proteasome. An alternative fate of these proteins is the aggresome pathway. The microtubule-organizing center (MTOC) transports unfolded proteins to lysosomes and are degraded through autophagy. Histone deacetylase 6 (HDAC6) deacetylates alpha-tubulin, which is thought to be a component of the MTOC. Recently, two small molecule inhibitors of the aggresome pathway and HDAC6 have been described. One inhibitor, tubacin, prevents deacetylation of alpha-tubulin and produces accumulation of polyubiquitinated proteins and apoptosis. Tubacin acts synergistically with the proteasome inhibitor, bortezomib, to induce cytotoxicity in one type of hematologic malignancy, multiple myeloma. The other, LBH589, is a pan HDAC inhibitor and hydroxamic acid derivative that induces apoptosis of multiple myeloma cells resistant to conventional therapies. In this review, we summarize recent reports on targeting the aggresome pathway and HDAC6 in hematologic malignancies.

The amount of astronomical data is rapidly growing as the progress of telescope technology and the detection technique of recent years. As a result, the way of traditional analysis is becoming insufficient for utilizing the large amount of data efficiently. The SuprimeCam, which is one of the instruments equipped with the Subaru telescope, has been generating 7 TB of public data since its start of operation. It is almost impossible to transfer all the data to the local machine to analyze them. It is, therefore, desirable to have an environment where the data is analyzed where it is stored. In addition, it is not easy to use the Subaru data for an researcher who is not familiar with the Subaru data reduction. To overcome these difficulties, we developed the server side data analysis system and applied GRID technology to construct the system that carry out multiple jobs on multiple servers. Integrating this system to the Japanese Virtual Observatory, a user can easily utilize the GRID system through the web browser interface.

Retention of hydrogen in co-deposits formed under high-density plasma discharge in TRIAM-1M was studied. In order to quantify the retained hydrogen, material probe experiments were performed under the high-density ( n ˜ e ∼ 10 19 m - 3 ) discharges. After the exposure to the plasma, the quantitative analysis of deposition, hydrogen retention, and microscopic modification of specimens were performed by means of ion beam analysis and transmission electron microscopy. The co-deposits mainly consisted of Mo. The deposition rate of Mo was about ten times higher than that of the low-density discharge case. The hydrogen concentrations (H/Mo) retained in the co-deposits were 0.06–0.17, which was much higher than that in bulk-Mo and almost equal to the low-density case. These results indicate that as long as the co-deposition layers are continuously formed, strong wall pumping in TRIAM-1M is maintained during the discharges.

In femtosecond degenerate four-wave mixing (FWM) spectroscopy for the exciton and biexciton system in a semiconductor β - ZnP 2 , we have observed that the spectrally resolved FWM signals from the exciton–biexciton transition exhibit a specific time profile consisting of a growing up and decay for negative and positive delay between two excitation pulses, respectively. The decay profile indicates unexpectedly much slower dephasing of the exciton–biexciton transition compared to 1s exciton polariton. The time profile is interpreted as the manifestation of local field renormalization due to many-body Coulomb correlation among carriers in β - ZnP 2 , which is made observable due to the narrow homogeneous linewidth of the exciton–biexciton transition.

In order to improve the critical current density ( J c ) and mechanical property of Bi-2223 sintered bulk, Ni wire meshes were added in the bulk. For fabricating large-sized cylindrical Bi-2223/Ni meshes composite, composing meshes are easy to produce compared with adding a lot of wires. The mesh concentration was 18 × 18 meshes/cm 2 using Ni wires of 0.25 mm in diameter. The Ni meshes were plated with Ag by 0.03 mm in thickness. We prepared the cylindrical sintered bulk for a current lead, 32 mm in outer diameter, 2 mm in thickness and 110 mm in length using a cold isostatic pressing (CIP) method. The samples were sintered at 845 °C for 50 h. After treatment again with CIP as an intermediate pressing, the samples were re-sintered. Small species were cut from the cylinder for measurement of critical current density ( J c ) at 77 K under self-field. There existed higher J c portions and low J c portions in the composite cylinder. Scanning electron microscope (SEM) observation showed that highly c -axis oriented and densely structured Bi-2223 plate-like grains could be formed around the interfacial region between the superconducting oxide and the Ag-plated Ni wires. There observed structural dislocation, which lead to low J c portions in the cylinder.

Glucocorticoid (GC)-evoked apoptosis of T-lymphoid cells is preceded by increases in the intracellular Ca2+ concentration ([Ca2+]i), which may contribute to apoptosis. This report demonstrates that GC-mediated upregulation of the bZIP transcriptional repressor gene, E4BP4, is dependent on [Ca2+]i levels, and correlates with GC-evoked apoptosis of GC-sensitive CEM-C7-14 cells. Calcium chelators EGTA and BAPTA reduced [Ca2+]i levels and protected CEM-C7-14 cells from Dex-evoked E4BP4 upregulation as well as apoptosis. In the GC-resistant sister clone, CEM-C1-15, Dex treatment did not induce [Ca2+]i levels, E4BP4 expression or apoptosis, however, the calcium ionophore A23187 restored Dex-evoked E4BP4 upregulation and apoptosis. CEM-C7-14 cells were more sensitive to GC-independent increases in [Ca2+]i levels by thapsigargin, and a corresponding increase in E4BP4 expression and cell death, compared to CEM-C1-15 cells, suggesting a direct correlation between [Ca2+]i levels, E4BP4 expression, and apoptosis.

Purpose: To evaluate the clinical outcomes of 48 Gy of three-dimensional stereotactic radiotherapy in four fractions for treating Stage I lung cancer using a stereotactic body frame. Methods and Materials: Forty-five patients who were treated between September 1998 and February 2004 were included in this study. Thirty-two patients had Stage IA lung cancer, and the other 13 had Stage IB lung cancer where tumor size was less than 4 cm in diameter. Three-dimensional treatment planning using 6–10 noncoplanar beams was performed to maintain the target dose homogeneity and to decrease the irradiated lung volume >20 Gy. All patients were irradiated using a stereotactic body frame and received four single 12 Gy high doses of radiation at the isocenter over 5–13 (median = 12) days. Results: Seven tumors (16%) completely disappeared after treatment (CR) and 38 tumors (84%) decreased in size by 30% or more (PR). Therefore, all tumors showed local response. During the follow-up of 6–71 (median = 30) months, no pulmonary complications greater than an National Cancer Institute-Common Toxicity Criteria of Grade 3 were noted. No other vascular, cardiac, esophageal, or neurologic toxicities were encountered. Forty-four (98%) of 45 tumors were locally controlled during the follow-up period. However, regional recurrences and distant metastases occurred in 3 and 5 of T1 patients and zero and 4 of T2 patients, respectively. For Stage IA lung cancer, the disease-free survival and overall survival rates after 1 and 3 years were 80% and 72%, and 92% and 83%, respectively, whereas for Stage IB lung cancer, the disease-free survival and overall survival rates were 92% and 71%, and 82% and 72%, respectively. Conclusion: Forty-eight Gy of 3D stereotactic radiotherapy in 4 fractions using a stereotactic body frame is useful for the treatment of Stage I lung tumors.

The bone marrow failure syndromes consist of a number of rare diseases, in which there is ineffective hematopoiesis by the bone marrow. Subsequently, absent or decreased production of a single cell line, single cytopenia, or of all cell lines, and pancytopenia, develops. The mechanisms of hematopoiesis and the defects that result in bone marrow failure are beginning to be better understood. This paper will review the genetic and molecular basis of several important bone marrow failure syndromes in children, Fanconi anemia, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, and severe congenital neutropenia, and the recent discoveries that have enhanced our understanding of the pathogenesis of these diseases.

In July 2002, a combination of underway mapping and discrete profiles revealed significant along-shore variability in the concentrations of manganese and iron in the vicinity of Monterey Bay, California. Both metals had lower concentrations in surface waters south of Monterey Bay, where the shelf is about 2.5 km wide, than north of Monterey Bay, where the shelf is about 10 km wide. During non-upwelling conditions over the northern broad shelf, dissolvable iron concentrations measured underway in surface waters reached 3.5 nmol L−1 and dissolved manganese reached 25 nmol L−1. In contrast, during non-upwelling conditions over the southern narrow shelf, dissolvable iron concentrations in surface waters were less than 1 nmol L−1 and dissolved manganese concentrations were less than 5 nmol L−1. A pair of vertical profiles at 1000 m water depth collected during an upwelling event showed dissolved manganese concentrations of 10 decreasing to 2 nmol L−1, and dissolvable iron concentrations of 12–20 nmol L−1 in the upper 100 m in the north, compared to 3.5–2 nmol L−1 Mn and ∼0.6 nmol L−1 Fe in the upper 100 m in the south, suggesting the effect of shelf width influences the chemistry of waters beyond the shelf. These observations are consistent with current understanding of the mechanism of iron supply to coastal upwelling systems: Iron from shelf sediments, predominantly associated with particles greater than 20 μm, is brought to the surface during upwelling conditions. We hypothesize that manganese oxides are brought to the surface with upwelling and are then reduced to dissolved manganese, perhaps by photoreduction, following a lag after upwelling. Greater phytoplankton biomass, primary productivity, and nutrient drawdown were observed over the broad shelf, consistent with the greater supply of iron. Incubation experiments conducted 20 km offshore in both regions, during a period of wind relaxation, confirm the potential of these sites to become limited by iron. There was no additional growth response when copper, manganese or cobalt was added in addition to iron. The growth response of surface water incubated with bottom sediment (4 nmol L−1 dissolvable Fe) was slightly greater than in control incubations, but less than in the presence of 4 nmol L−1 dissolved iron. This may indicate that dissolvable iron is not as bioavailable as dissolved iron, although the influence of additional inhibitory elements in the sediment cannot be ruled out.

We assessed the responses of zooplankton communities with different population densities of an invertebrate predator, Mesocyclops pehpeiensis, to insecticide (carbaryl, 0.5 mg L −1 ) in small-scale mesocosm tanks (20 L). Cladocerans were eliminated by carbaryl application at both high and low predator densities. The density of rotifers increased after the elimination of the cladocerans by carbaryl application at low-predator density but not at high-predator density. Carbaryl application increased the relative importance of predatory interactions in the zooplankton community. The results suggest that predator abundance can affect the response of a zooplankton community to carbaryl application through predation on surviving zooplankton. © 2005 Elsevier B.V. All rights reserved.

Purpose: To analyze the stereotactic radiotherapy (SRT) plans in terms of internal target volume (ITV) and organs at risk (OARs). Methods and Materials: Treatment planning and dose distributions were analyzed using dose-volume histograms (DVHs) of ITV and OARs in 37 patients, who were treated for a solitary lung tumor with SRT. The stereotactic body frame (SBF) was used for immobilization and accurate setup. Prescription dose was 48 Gy in four fractions at the isocenter. Results: Use of SBF limits the extent of the noncoplanar beam directions to prevent a collision with the Linac gantry. DVH analyses showed that the homogeneity index, defined as the ratio of maximum and minimum dose to ITV, ranged from 1.03 to 1.25 (mean, 1.12). The volume irradiated with 20 Gy or more (V 20 ) of the lung ranged from 0.3 to 11.6% (mean, 4.4%) of the whole lung volume. The maximum dose to the other OARs ranged from 0 to 11.8 Gy (mean, 0.5–2.7) per fraction. No clinically significant complications were encountered. Conclusions: Despite the limitation of the beam arrangement, a homogeneous target dose distribution, while avoiding high doses to normal tissues, was obtained.

SummaryCREB is a transcription factor that functions in glucose homeostasis, growth factor-dependent cell survival, and memory. In this study, we describe a role of CREB in human cancer. CREB overexpression is associated with increased risk of relapse and decreased event-free survival. CREB levels are elevated in blast cells from patients with acute myeloid leukemia. To understand the role of CREB in leukemogenesis, we studied the biological consequences of CREB overexpression in primary human leukemia cells, leukemia cell lines, and transgenic mice. Our results demonstrate that CREB promotes abnormal proliferation and survival of myeloid cells in vitro and in vivo through upregulation of specific target genes. Thus, we report that CREB is implicated in myeloid cell transformation.

The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment of human diseases. However, many of these proteins are from functional classes that have never been validated as viable candidates for the development of small molecule inhibitors. Thus, to exploit fully the potential of the Human Genome Project to advance human medicine, there is a need to develop generic methods of inhibiting protein activity that do not rely on the target protein’s function. We previously demonstrated that a normally stable protein, methionine aminopeptidase-2 or MetAP-2, could be artificially targeted to an Skp1-Cullin-F-box (SCF) ubiquitin ligase complex for ubiquitination and degradation through a chimeric bridging molecule or Protac (proteolysis targeting chimeric molecule). This Protac consisted of an SCFß-TRCP-binding phosphopeptide derived from I{kappa}B{alpha} linked to ovalicin, which covalently binds MetAP-2. In this study, we employed this approach to target two different proteins, the estrogen (ER) and androgen (AR) receptors, which have been implicated in the progression of breast and prostate cancer, respectively. We show here that an estradiol-based Protac can enforce the ubiquitination and degradation of the {alpha} isoform of ER in vitro, and a dihydroxytestosterone-based Protac introduced into cells promotes the rapid disappearance of AR in a proteasome-dependent manner. Future improvements to this technology may yield a general approach to treat a number of human diseases, including cancer.

The p55CDC (cell division cycle) protein is a key regulator of the cell cycle. p55CDC is related to both the CDC20 and the CDH1 proteins in yeast. p55CDC has been shown to activate the ubiquitin ligase anaphase promoting complex (APC), which is involved in degradation of proteins that control mitosis. To define the role of p55CDC during the mammalian cell cycle, we overexpressed this protein in the murine myeloid cell line 32Dcl3. 32Dcl3 cells are an ideal model system because these cells can be induced to proliferate, differentiate, or activate cellular programs leading to apoptosis. Our work suggests that p55CDC participates in cell growth, maturation, and death. Thus, p55CDC may play a more diverse role in modulating cellular functions in addition to controlling the cell cycle.

A large difference between properties of wall recycling in the continuous gas feed case (i.e. static condition) and the additional gas puff case (i.e. dynamic condition) has been observed. In the static condition, the effective particle confinement time, τ* p , increases almost linearly to about 10 s during the 1 min discharge. In the dynamic condition, τ* p is 0.2-0.3 s during the 1 min discharge. This difference of τ* p is also confirmed in the ultra-long discharge. τ* p in the static condition becomes ∼100 s before the global balance between particle absorption and release of the wall is achieved at t ∼ 30 min. τ* p in the dynamic condition is, however, still on the order of ∼0.3 s. The large difference between τ* p in the static and dynamic conditions is attributed to a reduction in the recycling coefficient due to enhanced wall pumping resulting from the gas puff.

This article concerns d–f heteronuclear complexes, focusing on recent progress in their synthesis, stereochemistry, magnetism, some other physicochemical properties, and potential use as new materials.

The budding yeast RENT complex, consisting of at least three proteins (Net1, Cdc14, Sir2), is anchored to the nucleolus by Net1. RENT controls mitotic exit, nucleolar silencing, and nucleolar localization of Nop1. Here, we report two new functions of Net1. First, Net1 directly binds Pol I and stimulates rRNA synthesis both in vitro and in vivo. Second, Net1 modulates nucleolar structure by regulating rDNA morphology and proper localization of multiple nucleolar antigens, including Pol I. Importantly, we show that the nucleolar and previously described cell cycle functions of the RENT complex can be uncoupled by a dominant mutant allele of CDC14. The independent functions of Net1 link a key event in the cell cycle to nucleolar processes that are fundamental to cell growth.

The effects of thickness-extensional mode resonance oscillation (TERO) on the catalytic activity for CO oxidation of thin TiO 2 and NiO films deposited on a z -cut LiNbO 3 ( z -LN) single crystal were investigated. TERO at 3 W caused 4 – 7-fold increases in the catalytic activity of TiO 2 / z -LN and NiO/ z -LN and remarkable decreases in the activation energy of the reaction. Vertical lattice displacement by TERO was decreased remarkably by the presence of the metal oxides. The catalyst activation is due to the interactions of TERO with the carriers in the semiconductor metal oxides.

We present a perturbative calculation of the renormalization constants for the $\Delta B=2$ four-quark operators, which is needed to evaluate the bag parameters $B_B$ and $B_S$ in lattice QCD. The one-loop coefficients are calculated for the $O(1/M)$ NRQCD heavy quark action and the $O(a)$-improved Wilson action for light quark. Using these coefficients, which remove $O(\alpha_s/aM)$ error, we reanalyze our previous calculation of the bag parameters., Comment: Lattice 2000 (Heavy Quark Physics), 5 pages, LaTeX

We fabricated bifacial-type rear-floating-emitter solar cells and triode solar cells from several types of wafers and investigated the light degradation of solar-cell performance. Rear efficiency of a rear-floating-emitter bifacial solar cell degrades in proportion to bulk-minority carrier lifetime. This degradation of cell efficiency is much larger than that reported so far. Bifacial cells must therefore be made from wafers that are not degraded by light. And it was found that magnetic-field-applied CZ wafers or gallium-doped CZ wafers meet this requirement very well. Three-terminal measurement showed that light degradation does not have much influence on rear efficiency of triode cells compared with that of two-terminal bifacial cells.

The surface deflections in an automobile panel pressed by a punch have irregular distributions of configuration, inclined angles and curvature along a line. Here, a simple quantitative and convenient measurement method is proposed to measure and evaluate the surface deflections of sheet metal and the associated location directly after press forming by using an image-sensing camera system. First, the mathematical equations of optical geometry are formulated, and the implementation of the measuring procedure is given for quantitative measurement. Second, its effectiveness is verified and discussed in relation to the results of experiments. The merit of this method is its ability to measure the reflected point of light along a line on a mirror-like surface of sheet metal directly, where the surface deflections can be evaluated by comparison with the levels recorded previously.

PrCo2Si2 has a collinear antiferromagnetic structure with a wave vector Q 1 =(0, 0, 1) for T Q 2 =(0, 0, 25/27) for T1⩽T Q 3 =(0, 0, 7/9) for T2⩽T

We have studied the new dry etching using a multiply-charged ion beam of which potential energy increases with its charge state, and multiply-charged ion has a high potential energy than a single charged ion. This paper proposes a new dry etching of semiconductor materials using the potential energy of the multiply-charged ion beam. When the multiply-charged Ar ions irradiate GaAs surface, not only the physical sputtering in vacuum but also the ion-induced chemical etching in Cl2 ambient is enhanced. This enhancement is found to be remarkable at the high potential energy region with a higher charge state.

Flow injection analysis with chemiluminescence detection (FIA–CL) via the reaction of copper with 1,10-phenanthroline was used for the determination of copper complexation in seawater. A detection limit of 0.1 nM Cu in undiluted seawater without sample preconcentration was obtained. Copper speciation was assessed by titrating natural seawater ligands with added copper. This method was used to measure copper complexation throughout the water column in Monterey Bay, California. Two ligand classes were identified: a strong ligand (L1), ranging in concentration from 1.3 to 3.1 nM, and a weaker ligand (L2), ranging from 9.4 to 25.6 nM. The average conditional stability constant for the strong ligand was log K 1 ′ 13.1±0.4 and for the weaker ligand log K 2 ′ 9.4±0.6. These measurements are in good agreement with complexation studies previously performed using established methods. This technique may eventually be adapted for in situ complexation measurements that can be used to monitor natural spatial and temporal variations in copper complexation, as well as coastal ecosystem responses to urban and industrial change.

NdCo 2 Si 2 has a collinear antiferromagnetic structure with a wave vector Q 1 =(0, 0, 1) for T T 1 =16 K, a high-order commensurate one with Q 2 =(0, 0, 13 14 ) for T 1 ⩽ T T 2 =24 K and with Q 3 =(0, 0, 11 14 ) for T 2 ⩽ T T N =32 K. Molecular field calculations of the moment arrangements and magnetization processes of the compound were carried out and the field-temperature phase diagram was reproduced. The magnetic transition at T 2 is discussed in connection with the fact that the third harmonics 3 Q 2 of the magnetic structure for T 1 ⩽ T T 2 is equivalent to the fundamental wavevector Q 3 for T 2 ⩽ T T N .

During the second leg (PlumEx) of the 1993 IRONEX cruise, the partial pressure of CO 2 and the concentrations of nitrate and silicate in the surface waters around the Galapagos Islands were continuously measured using automated underway systems. Based on salinity-versus-constituent mixing diagrams, physical mixing processes dominate the pCO 2 and nutrient distributions upstream of the Galapagos Islands. Downstream of the islands, slight removal of nitrate and CO 2 can be discerned because of the high resolution of the underway measurements. The high spatial resolution of the underway measurements allowed evaluation of fine features such as sharp fluorescence peaks on the “warm” side of frontal boundaries. In the waters immediately adjacent to Fernandina and Isabela islands (Bolivar channel), dramatic drawdown of pCO 2 and nutrients was measured, coincident with the highest measured levels of iron (3 nM) and chlorophyll (>13 μg l -1 ) (Martin et al., 1994). The nearly constant alkalinity of the waters was combined with the measured pCO 2 to calculate total carbon dioxide in the waters. Based on mixing diagrams, the ratio of ΔTCO 2 to ΔNO - 3 was found to be highly variable, ranging from approximately 6.4 to >10 in the waters near Isabela Island. The ratio of ΔTCO 2 to ΔNO - 3 is approximately 8.5 in the waters west of the Galapagos where slight removal of nitrate and TCO 2 occurs. In these waters, the physical process of mixing and CO 2 degassing due to warming of the water becomes significant relative to the biological uptake and the ratio is driven higher.

p55Cdc is a mammalian homologue of a family of cell cycle proteins from widely divergent species, which contains WD repeats and has been implicated in cell cycle-regulated ubiquitin-mediated proteolysis. p55Cdc is highly expressed in proliferating but not in differentiated or growth-arrested cells. The expression, phosphorylation, and degradation of this protein have been shown to be cell cycle-regulated. We analyzed a 5.3-kb genomic region that contains the entire rat p55Cdc gene. The gene contains 10 exons ranging in size from 97 to 373 bp. The promoter region has a TATA box, four E-box consensus sequences, and potential binding sites for cell cycle-specific transcription factors. In transient transfection assays, a construct containing a 1000-nucleotide p55Cdc promoter region upstream of the chloramphenicol acetyltransferase reporter gene demonstrated a 12-fold increase in transcriptional activity. Finally, using radiation hybrid mapping techniques, we localized this gene to the human chromosome, 9q13–21.

We thank the families whose members have carried the burden of LD; without their cooperation this study would not have been possible. We also gratefully acknowledge the cooperation and assistance of Joan Spellman, Bernadette Sakamoto, and Susan G. Pietsch-Escueta, who helped recruit families and coordinate family studies. Our study was approved by the Human Subjects Protection Committee at the UCLA School of Medicine and the West Los Angeles DVA Medical Center. Each participating patient or, in the case of minors or deceased relatives, the responsible adult, signed an informed-consent form. Our project was supported by NIH-NINDS program project 5PO1-NS21908 (to A.V.D.-E.), by special contributions from Mrs. A. Malenfant and the Quebec Lafora's Disease Organization, and by Mrs. Vera Faludi of Sweden.

To improve the cell performance of single-crystal silicon solar cells, the process conditions have been optimized by monitoring the bulk lifetime after each thermal step in the cell fabrication process. The emitter geometry, i.e., front and rear contact size and pitch were optimized, and the cells were fabricated through a set of environmentally considered processes, especially for surface treatment, oxidation, diffusion, and electrode fabrication. Conversion efficiency of 22.3% in a 4 cm 2 cell, and 22.6% in a 1 cm 2 cell, was attained, respectively, with structural features of SiO 2 single-AR, “inverted-pyramid” fron texture, point-contact with line-emitter for front electrodes, and locally diffused BSF for rear contacts.