Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.).
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this ...
p53 is one of the most mutated tumor suppressors in human cancers and as such has been intensively studied for a long time. p53 is a major orchestrator of the cellular response to a broad array...Full Text Available
The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53...Full Text Available
IL-4-induced Stat6 signaling is active in a variety of cell types and plays a role in cell proliferation/growth and resistance to apoptosis. Using EMSA, we identified differential IL-4/Stat6 activities in colorectal cancer cell lines, HT-29 being active Stat6"h"i"g"h phenotype and Caco-2 being defective Stat6"n"u"l"l phenotype, respectively. Active Stat6"h"i"g"h HT-29 cells exhibited resistance to apoptosis by flowcytometry and aggressive metastasis by Transwell assay compared with defective Stat6"n"u"l"l Caco-2 cells. Comparing one another using RT-PCR, Stat6"h"i"g"h HT-29 cells expressed more mRNA of anti-apoptotic and pro-metastatic genes Survivin, MDM2, and TMPRSS4, while Stat6"n"u"l"l Caco-2 cells expressed more mRNA of pro-apoptotic and anti-metastatic genes BAX, CAV1, and P53, respectively. This is the first study describing correlations of IL-4/Stat6 activities with ...
Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low ...
We previously reported that acetaminophen (APAP) caused apoptosis of C6 glioma cells. Therefore, we hypothesized that the level of p53, which usually stimulates apoptosis, might be increased...Full Text Available
Five studies show that disabling p53, an essential tumour-suppressor protein, improves the efficiency of stem-cell production. Are these results a ‘heads up’ that cancer cells...Full Text Available
p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest,...Full Text Available
A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important...Full Text Available
Aim—To study p53 expression in relation to proliferative status in normal and nondysplastic, dysplastic and malignant lesions of the oral mucosa.Method—The...Full Text Available
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available
To analyze the proposed growth-inhibitory function of wild-type p53, we compared simian virus 40 (SV40) DNA replication in primary rhesus monkey kidney (PRK) cells, which express wild-type p53, and...Full Text Available
The tumor suppressor p53 is often inactivated in breast cancer cells because the overexpression of its repressors (e.g., MDM2 and MDMX). Restoration of p53 activity by small molecules through counteracting...Full Text Available
Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by ...
Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits...Full Text Available
Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available
The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available
AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb,...Full Text Available
We present changes in the p53 gene in a group of 70 thyroid tumours and 40 blood samples obtained from children from Belarus. Three thyroid tumours show a polymorphism in exon 6 (codon 213) and 5 tumours show a polymorphism in intron 6, 37 bp upstream to the 5'-end of exon 7. Only one patient has a mutation in exon 7 (codon 258) resulting in an amino acid substitution in the protein p53. The distribution of polymorphisms in the 40 blood samples was as follows: three patients had a polymorphism in exon 6 and two persons had a polymorphism in intron 6. One polymorphism in intron 6 was also found in the group of 30 healthy children from Belarus. The fact that the differences in the sequence in p53 found in the tumours was also seen in the blood of these patients demonstrates that they are polymorphisms not induced by radiation exposure. It is difficult to conclude, ...
Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability,...Full Text Available
BackgroundCyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2...Full Text Available
Identification of factors that determine individual patient risk for recurrence and progression in superficial papillary carcinoma of the bladder is a subject of extensive research as it would be a major outcome in patient management. It has been well recognized that traditional prognostic markers as tumor grade and stage are not accurate enough in predicting biological behavior. A large number of markers have been investigated as potential prognostic factors and relatively few can help in predicting outcome. Material and Methods: Forty-nine cases undergoing complete transurethral resection for primary superficial papillary transitional cell carcinoma were subjected to clinicopathologic evaluation as well as immunohistochemical staining for p53, bcl-2, cytokeratin 20 and Ki-67. The CAS-200 image analyzer was used to estimate the Ki-67 labeling index. Results: Recurrence was observed in 19 cases (38.8%) and progression in 7 cases (14.3%) with a ...
Purpose: To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Methods and Materials: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using ...
TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin se...
Diffraction by an impermeable scatterer in ?3 with a Dirichlet boundary condition is considered. It is shown that the null field equation is equivalent to the original diffraction problem. The general theoretical constructions are illustrated by analyzing the excitation of a sphere by a point source. The evolution of the residual of the null field equation as the scatterer surface is approached by an auxiliary surface is estimated.
Purpose: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. Methods and Materials: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. Results: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue of Group 2 patients showed similar pattern levels (high and low) as that of superoxide dismutase/catalase. The association of ...
A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila....Full Text Available
This report presents the results of a study of the Japanese MLU magnetic-levitation (maglev) system. The development of the MLU system is reviewed, and the dynamic circuit model then is introduced and applied to the figure-eight-shaped null-flux coil suspension system. Three different types of figure-eight-shaped null-flux suspension systems are discussed in detail: (1) the figure-eight-shaped null-flux coil suspension system without cross-connection; (2) the combined suspension and guidance system; and (3) the combined propulsion, levitation, and guidance system. The electrodynamic-suspension maglev systems developed in Japan seem to be very promising and could result in a commercial application in the near future.
Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)
Cell extracts of the thermophile Clostridium thermohydrosulfuricum catalyzed the phosphorylation by (..gamma..-/sup 32/P)ATP of several endogenous proteins with M/sub r/s between 13,000 and 100,000. Serine and tyrosine were the main acceptors. Distinct substrate proteins were found in the soluble (e.g., proteins p66, p63, and p53 of M/sub r/s 66,000, 63,000, and 53,000, respectively) and particulate (p76 and p30) fractions, both of which contained protein kinase and phosphatase activity. The soluble fraction suppressed the phosphorylation of particulate proteins and contained a protein kinase inhibitor. Phosphorylation of p53 was promoted by 10..mu..M fructose 1,6-bisphosphate or glucose 1,6-bisphosphate and suppressed by hexose monophosphates, whereas p30 and p13 were suppressed by 5 ..mu..M brain (but not spinach) calmodulin. Polyamines, including the odd polyamines characteristic of thermophiles, ...
The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by ...
Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.
Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision ...
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce ...
Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in homozygous null progeny at lower frequencies than expected. Genotyping offspring at pre-, peri-, and postnatal stages revealed that over half of homozygous null mutants die in the early postnatal stages. To investigate the reasons for this early postnatal lethality, we analyzed in detail different parameters in the initial hours after birth. POMC null mutants born to heterozygous dams presented at birth with corticosterone levels no different from wildtype littermates, were euglycemic, and had normal liver glycogen stores. However, already 30 min after birth corticosterone levels dropped by 80% and were undetectable thereafter, while corticosterone levels in wildtype animals increased during postnatal hours. Circulating adrenaline was almost below detection 1h after birth. Blood glucose levels fell sharply in all genotypes within 30 min after birth; ...
Summary: Analysis of biological networks requires assessing the statistical significance of network-based predictions by using a realistic null model. However, the existing network null model, switch randomization, is unsuitable for metabolic networks, as it does not include physical constraints and generates unrealistic reactions. We present JMassBalance, a tool for mass-balanced randomization and analysis of metabolic networks. The tool allows efficient generation of large sets of randomized networks under the physical constraint of mass balance. In addition, various structural properties of the original and randomized networks can be calculated, facilitating the identification of the salient properties of metabolic networks with a biologically meaningful null model. Availability and Imp...
We investigate the extent to which the pure magnification effect of gravitational lensing can be extracted from galaxy clustering statistics, by a nulling method which aims to eliminate terms arising from the intrinsic clustering of galaxies. The aim is to leave statistics which are free from the uncertainties of galaxy bias. We find that nulling can be done effectively, leaving data which are relatively insensitive to uncertainties in galaxy bias and its evolution, leading to cosmological parameter estimation which is effectively unbiased. This advantage comes at the expense of increased statistical errors, which are in some cases large, but it offers a robust alternative analysis method to cosmic shear for cosmological imaging surveys designed for weak lensing studies, or to full modelling of the clustering signal including magnification effects.
BackgroundSome epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results...Full Text Available
Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null ...Full Text Available
Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes. Keap1-null mice are lethal by weaning age due...Full Text Available
BackgroundDeveloping lepidopteran microsatellite DNA markers can be problematical, as markers often exhibit multiple banding patterns and high frequencies of non-amplifying "null"...Full Text Available
Psychological illness influences the experience and expression of pain and disability. We tested three null hypotheses: (1) patients with nonspecific pain (medically unexplained and idiopathic) and...Full Text Available
The connection between W-algebras and the algebra of differential operators is conjectured. The bosonized representation of the differential operator algebra with c=-2n and all the subalgebras are examined. The degenerate representations and null-state classifications for c=-2 are presented. (orig.).
Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency...Full Text Available
Growing evidences indicate that proteases are implicated in adipogenesis and in the onset of obesity. We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white...Full Text Available
The global acquired immunodeficiency syndrome (AIDS) pandemic is thought to have arisen by the transmission of human immunodeficiency virus (HIV-1)-like viruses from chimpanzees in southeastern...Full Text Available
Pion interferometry (HBT of A+A) data have posed a thorn in the theoretical interpretation of AA collisions at RHIC (#sq root#s = 130 AGeV). How can R_o_u_t #approx# R_s_i_d_e #approx# R_l_o_n_g and remain so between AGS and RHIC? Where is the QGP Stall? Can elephants hide along the x_0"+ dimension? We rummage old hydrodynamic scenarios and uncover some previously ignored NULL solutions. (author)
DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...
[F-18]FDG PET brain imaging is an accurate predictor of primary brain tumor grading and prognosis. The purpose of this study was to evaluate simplified [F-18]FDG PET metabolic indices as indicators of proliferative activity of brain tumor cells. Twenty-five patients with glioma were studied with [F-18]FDG PET. From the tissue radioactivity ratios, following tumor metabolic indices were calculated: 1) the tumor-to-whole brain ratio (T/WB), 2) the ratio of tumor-to-contralateral gray matter at the level of centrum semiovale (T/GM), 3) the ratio of tumor-to-contralateral white matter at the level of centrum semiovale (T/WM), 4) the tumor-to-ipsilateral cerebella ratio (T/iCB) and 5) the tumor-to-contralateral cerebellar ratio (T/cCB). A standardized threshold method was used to define ROIs in the tumor areas having representative metabolic activites. Correlations of the tumor metabolic indices with histologic grade, Ki-67 labeling index (Ki-67 LI), ...
Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can ...
The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of #gamma# -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in #gamma# -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated mice ...
Little clinical evidence has been provided to show the minimization of radiation resistance of tumors using high linear energy transfer radiation. We therefore investigated the radiobiological and molecular pathological aspects of carbon beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the cervix were treated using a carbon beam and 50 control patients with SCC of the cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before radiotherapy and 5 and 15 days after therapy initiation were investigated using immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI) and p53 LI during carbon and photon beam therapies. However, for carbon beam therapy, the mean p27 LI significantly decreased from 25.2% before treatment to 18.6% on the 5th day after treatment initiation, followed by a significant increase to 36.1% on the 15th day. In ...
Primary adenocarcinomas of the urinary bladder are uncommon, and the molecular pathways are currently not well defined. In this study, we assessed the association between biologic markers and clinicopathologic characteristics in a cohort of 21 patients with primary urinary bladder adenocarcinoma. Immunohistochemical staining for cell cycle-specific markers, including p53, p21, p27, Ki-67, and cyclin E, were performed on sections of a tissue microarray construct. The tumors were high grade in 12 (57%) and pT2 or higher in 18 (86%); lymph nodes were involved in 6 cases (29%); and there was pathologic evidence of schistosomiasis in 14 (67%). The best prognostic combination of markers was combined alterations in p27 and Ki-67 and was associated with stage (P = .012), grade (P = .005), DNA ploidy (P = .005), and lymph node involvement (P = .04). Stage, lymph node involvement, combined alterations of p27 and Ki-67, and combined alterations of all 5 ...
This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also ...
We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling...Full Text Available
An apparently significant result in an experiment to search for tachyons in the interval of time immediately preceding in the arrival of air showers of energy approximately 10"1"5 eV is considered. Several similar experiments have been completed, all of which have yielded null results. The original data of the foregoing reference have been re-examined and it is shown that an artifact of the apparatus was contributing to the original apparently significant results. (orig./BJ).
Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165 (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1 null embryos display vascular...Full Text Available
Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 45 genes. Using homozygosity mapping, we identified a ∼4 Mb homozygous region...Full Text Available
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain ...
Cytomegalovirus (CMV)-seropositive patients with ESRD may have more CD4+ T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null) than CMV-seronegative patients. Increased...Full Text Available
Abstract Polycystic kidney diseases (PKD) are inherited disorders characterized by fluid-filled cysts primarily in the kidneys. We previously reported differences between the expression of Cux1, p21, and p27 in the cpk and Pkd1 null mouse models of PKD. Embryonic lethality of Pkd1 null mice limits its study to early stages of kidney development. Therefore, we examined mice with a collecting duct specific deletion in the Pkd1 gene. Cux1 was ectopically expressed in the cyst lining epithelial cells of newborn, P7 and P15 Pkd1CD mice. Cux1 expression correlated with cell proliferation in early stages of cystogenesis, however, as the disease progressed, fewer cyst lining cells showed increased cell proliferation. Rather, Cux1 expression in late stage cystogenesis was associated with increased ...
A construction of a W_3-algebra for the SU(3) parafermion is proposed. The details of the calculation are given, in which the Z-algebra technique is used instead of the popular free field realization. We find that the W_3-algebra is closed at level k=3, and the central charge of the underlying algebra is different from known series of Fateev-Lykyanov W-algebras; as a by-product we get a field T"("4")(z), whose conformal dimension is 4, and is null at k=3. ((orig.)).
Solutions are obtained for the Einstein field equations governing 40 rotating and time-dependent Bianchi type-IX cosmologies with thermal and nonthermal perfectly fluid sources. Some general properties of the solutions are discussed, and the exact computational details are given in a companion paper. All the cosmologies have spacelike, timelike or null-like homogeneous hypersurfaces depending on whether the constant alpha is less than or greater than one. The pressure of the cosmologies is assumed to be zero, and the energy density is less than zero. 9 references.
A method is presented for estimating the background at a given location on a sky map by interpolating the estimated background from a set of concentric annuli which surround this location. If the background is nonuniform but smoothly varying, this method provides a more accurate (though less precise) estimate than can be obtained with a single annulus. Several applications of multi-annulus background estimation are discussed, including direct testing for point sources in the presence of a nonuniform background, the generation of "surrogate maps" for characterizing false alarm rates, and precise testing of the null hypothesis that the background is uniform.
We consider light waves propagating clockwise and other light waves propagating counterclockwise around a closed path in a plane (theoretically with the help of stationary mirrors). The time difference between the two light propagating path orientations constitutes the Sagnac effect. The general relativistic expression for the Sagnac effect is discussed. It is shown that a gravitational wave incident to the light beams at an arbitrary angle will not induce a Sagnac effect so long as the wave length of the weak gravitational wave is long on the length scale of the closed light beam paths. The gravitational wave induced Sagnac effect is thereby null.
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid transcription factor ...
Some papers appearing in the two leading clinical journals of our specialty have fundamental defects in design, statistical analysis, and reporting. Actual publications are used to illustrate what investigators should and should not do, from initial planning through to their finished manuscript. A more detailed discussion of the most common statistical methods used in reproductive research is given as an online supplement. Some of these deficiencies illustrate the importance of registry of all study parameters for randomized clinical trials, a process covered in greater detail in an accompanying review and required for those manuscripts to be considered. Authors and reviewers need to be more aware of these requirements and common errors and pitfalls so that only quality manuscripts are pub...
An apparently significant result in an experiment to search for tachyons in the interval of time immediately preceding the arrival of air showers of energy greater than 10"1"5 eV has been reported by Clay and Crouch (Clay, R.W. and Crouch, P.C., 1974, Nature, vol.248,28-30). Several similar experiments have been completed, all of which have yielded null results. The original data of Clay and Crouch have been re-examined and it is shown that an artifact of the apparatus was contributing to the original, apparently significant, result. An upper limit estimate shows that the number of tachyons is less than the number of hadrons of energy greater than 100 GeV in showers of average size N = 6 x 10"5 particles. (author).
As a consequence of the close integration of cattle into the food chain of humans, forensically relevant cases involving cattle (Bos taurus) DNA analysis are common. However, scientific publications reporting the information content of the commonly used bovine short tandem repeat (STR) loci remains scarce. Population studies were performed for 16 polymorphic STR loci (BM1818, BM1824, BM2113, CSRM60, CSSM66, ETH3, ETH10, ETH225, HAUT27, ILSTS006, INRA023, SPS115, TGLA53, TGLA122, TGLA126, and TGLA227) including 4,162 randomly selected cattle representing 20 distinct breeds. The power of parental exclusion, expected and observed heterozygosity, probability of identity, and non-amplifying (?null?) allele frequencies were calculated. Major differences existed in the information content between...
Lie group methods provide a valuable tool for examininginvariance and non-uniqueness associated with geophysical inverseproblems. The techniques are particularly well suited for the study ofnon-linear inverse problems. Using the infinitesimal generators of thegroup it is possible to move within the null space in an iterativefashion. The key computational step in determining the symmetry groupsassociated with an inverse problem is the singular value decomposition(SVD) of a sparse matrix. I apply the methodology to the eikonal equationand examine the possible solutions associated with a crosswelltomographic experiment. Results from a synthetic test indicate that it ispossible to vary the velocity model significantly and still fit thereference arrival times. the approach is also applied to data fromcorosswell surveys conducted before and after a CO2 injection at the LostHills field in California. The results highlight the fact that a faultcross-cutting the region ...
The drift-kink instability in field-reversed configurations with a beam component is investigated by means of a three-dimensional particle simulation. The unstable mode with the toroidal mode number n=4 grows with the rate {gamma} {approx} 0.1 - 1.0{omega}{sub ci} for a strong beam current and deforms the plasma profile along the beam orbit in the vicinity of the field-null line. This mode is nonlinearly saturated as a result of the relaxation of current profile. Both the saturation level and the growth rate tend to increase as the ratio of the beam current to the plasma current I{sub b}/I{sub p} increases. It is also found that there is a threshold value of the beam velocity {upsilon}{sub b} {approx} {upsilon}{sub Ti} (ion thermal velocity) for the excitation of the instability. (author)
The detection of a stochastic background of gravitational waves could significantly impact our understanding of the physical processes that shaped the early Universe. The challenge lies in separating the cosmological signal from other stochastic processes such as instrument noise and astrophysical foregrounds. One approach is to build two or more detectors and cross correlate their output, thereby enhancing the common gravitational wave signal relative to the uncorrelated instrument noise. When only one detector is available, as will likely be the case with the Laser Interferometer Space Antenna (LISA), alternative analysis techniques must be developed. Here we show that models of the noise and signal transfer functions can be used to tease apart the gravitational and instrument noise contributions. We discuss the role of gravitational wave insensitive "null channels" formed from particular combinations of the time delay interferometry, and derive a new combination ...
A prescription is given for computing anomalous dimensions of single trace operators in SYM at strong coupling and large $N$ using a reduced model of matrix quantum mechanics. The method involves treating some parts of the operators as "BPS condensates" which, in certain limit, have a dual description as null geodesics on the $S^5$. In the gauge theory, the condensate is similar to a representative of the chiral ring and it is described by a background of commuting matrices. Excitations around these condensates correspond to excitations around this background and take the form of ``string bits" which are dual to the "giant magnons" of Hofman and Maldacena. In fact, the matrix model approach gives a {\\it quantum} description of these string configurations and explains why the infinite momentum limit suppresses the quantum effects. This method allows, not only to derive part of the classical sigma model Hamiltonian of the dual string (in the infinite momentum ...
Abstract in english Functional properties of soy proteins for food are closely related to the composition of their storage protein subunits. Using base excision sequence scanning (BESS), we show that the absence of the A4 peptide in the G4 glycinin subunit of the soybean (Glycine max L.) cultivar Enrei was caused by the same point mutation in the Gy4 gene as previously reported in the soybean cultivar Raiden. Although the genetic relationship between Raiden and Enrei is not known, the same p (more) oint mutation in their Gy4 genes may indicate that they probably share a related origin. The application of BESS to identify single nucleotide polymorphisms (SNPs) as co-dominant markers for marker-assisted selection (MAS) of a recessive null allele is also discussed.
Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after ...
Because of the equivalence principle, a global measurement is necessary to distinguish gravity from acceleration of the reference frame. A gravity gradiometer is therefore an essential instrument needed for precision tests of gravity laws and for applications in gravity survey and inertial navigation. Superconductivity and SQUID (superconducting quantum interference device) technology can be used to obtain a gravity gradiometer with very high sensitivity and stability. A superconducting gravity gradiometer has been developed for a null test of the gravitational inverse-square law and space-borne geodesy. Here we present a complete theoretical model of this instrument. Starting from dynamical equations for the device, we derive transfer functions, a common mode rejection characteristic, and an error model of the superconducting instrument. Since a gradiometer must detect a very weak differential gravity signal in the midst of large platform accelerations and other ...
The DARWIN mission is an Infrared free flying interferometer mission based on the new technique of nulling interferometry. Its main objective is to detect and characterize other Earth-like planets, analyze the composition of their atmospheres and their capability to sustain life, as we know it. DARWIN is currently in definition phase. This PhD work that has been undertaken within the DARWIN team at the European Space Agency (ESA) addresses two crucial aspects of the mission. Firstly, a DARWIN target star list has been established that includes characteristics of the target star sample that will be critical for final mission design, such as, luminosity, distance, spectral classification, stellar variability, multiplicity, location and radius of the star. Constrains were applied as set by planet evolution theory and mission architecture. Secondly, a number of alternative mission architectures have been evaluated on the basis of interferometer response as a function ...
We study an exactly solvable model where an uniformly accelerated detector is linearly coupled to a massless scalar field initially in the Minkowski vacuum. Using the exact correlation functions we show that as soon as the coupling is switched on one can see information flowing from the detector to the field and propagating with the radiation into null infinity. By expressing the reduced density matrix of the detector in terms of the two-point functions, we calculate the purity function in the detector and study the evolution of quantum entanglement between the detector and the field. Only in the ultraweak coupling regime could some degree of recoherence in the detector appear at late times, but never in full restoration, as an earlier work seems to suggest. We explicitly show that under the most general conditions the detector never recovers its quantum coherence and the entanglement between the detector and the field remains large at late times. To the extent ...
The authors present arguments against nuclear energy and pro renewable energy sources. Thus, the water used in Uranium mining and primary ore processing becomes contaminated in long lived radioisotopes and so a threat for local ecosystems and communities. Then, during the fabrication, enrichment, and handling of nuclear fuel the workers are exposed to radiations and dangerous accidental radioactive leaks can occur. But, by far, the most menacing aspect of nuclear power exploitation remains the human errors in operating the nuclear plants which can result in major accidents like that from Chernobyl which spread radioactivity all over the Europe. The equipment used in nuclear facilities which is highly contaminated as well as the burned fuel implies transportation and long term storage which also present high risks. The major advantage of the nuclear energy consists in its very low environment impact and its null contribution to the greenhouse effect. In contrast, ...
We present a showcase for deriving bounds on the neutrino masses from laboratory experiments and cosmological observations. We compare the frequentist and Bayesian bounds on the effective electron neutrino mass m_beta which the KATRIN neutrino mass experiment is expected to obtain, using both an analytical likelihood function and Monte Carlo simulations of KATRIN. Assuming a uniform prior in m_beta, we find that a null result yields an upper bound of about 0.17 eV at 90% confidence in the Bayesian analysis, to be compared with the frequentist KATRIN reference value of 0.20 eV. This is a significant difference when judged relative to the systematic and statistical uncertainties of the experiment. On the other hand, an input m_beta=0.35 eV, which is the KATRIN 5sigma detection threshold, would be detected at virtually the same level. Finally, we combine the simulated KATRIN results with cosmological data in the form of present (post-WMAP) and future (simulated ...
The UTST (University of Tokyo Spherical Tokamak) device was constructed for the purpose of exploring the formation of ultra-high beta ST (Spherical Tokamak) plasma using the double null plasma merging method. When two plasmas merge together to form a single plasma, magnetic field lines reconnect, and the magnetic field energy is converted to the plasma kinetic energy, increasing the plasma beta. The merging start-up has been demonstrated in the TS-3/4, START and MAST devices using coils inside the vacuum vessel and TS-3 plasma obtained 50% beta. In order to demonstrate the start-up in a more reactor relevant situation, UTST has all poloidal field coils outside the vacuum vessel. The first plasma experiment on the UTST was performed from December, 2007. In the result, the plasma obtained 10 kA by using only outer PF coils and single ST was generated at the lower area (z=-0.3 - -1.0[m]) close to a washer gun. This result suggests that another washer gun on the top of ...
A new double-null, slotted divertor configuration will be installed for the DIII-D Radiative Divertor Program at General Atomics in late 1996. Four cryocondensation pumps, three new and one existing, will be part of this new divertor. The purpose of the pumps is to provide plasma density control and to limit the impurities entering the plasma core by providing pumping at each divertor strike point. The three new pumps are based on the design of the existing pump, installed in 1992 as part of the Advanced Divertor Program. The pump continues to operate successfully. The new pumps require geometry modifications to the original design. Therefore, extensive modal and dynamic analyses were performed to determine the behavior of these pumps and their helium and nitrogen feed lines during disruption events. Thermal and fluid analyses were also performed to characterize the helium two-phase flow regime in the pumps and their feedlines. A flow testing program was completed ...
A new double-null, slotted divertor configuration will be installed for the DIII-D Radiative Divertor Program at General Atomics in late 1996. Four cryocondensation pumps, three new and one existing, will be part of this new divertor. The purpose of the pumps is to provide plasma density control and to limit the impurities entering the plasma core by providing pumping at each divertor strike point. The three new pumps are based on the design of the existing pump, installed in 1992 as part of the Advanced Divertor Program. The new pumps require geometry modifications to the original design. Therefore, extensive modal and dynamic analyses were performed to determine the behavior of these pumps and their helium and nitrogen feed lines during disruption events. Thermal and fluid analyses were also performed to characterize the helium two-phase flow regime in the pumps and their feedlines. A flow testing program was completed to test the change in geometry of the pump ...
A new double-null, slotted divertor configuration will be installed for the DIII-D Radiative Divertor Program at General Atomics in late 1996. Four cryocondensation pumps, three new and one existing, will be part of this new divertor. The purpose of the pumps is to provide plasma density control and to limit the impurities entering the plasma core by providing pumping at each divertor strike point. The three new pumps are based on the design of the existing pump, installed in 1992 as part of the Advanced Divertor Program. The pump continues to operate successfully. The new pumps require geometry modifications to the original design. Therefore, extensive modal and dynamic analyses were performed to determine the behavior of these pumps and their helium and nitrogen feed lines during disruption events. Thermal and fluid analyses were also performed to characterize the helium two-phase flow regime in the pumps and their feedlines. A flow testing program was completed ...
The paper describes a concept of extracting fusion power from D-{sup 3}He fueled IEC (Inertia Electrostatic Configuration) devices. The fusion system consists of a series of fusion modules and direct energy converters at an end or at both ends. This system of multiple units is linear and is connected by a magnetic field. A pair of coils anti-parallel to the magnetic field yields a field-null domain at the center of each unit as required for IEC operation. A stabilizing coil installed between the coil pairs eliminates the strong attractive force between the anti-parallel coils. Accessible regions for charged particle trajectories are essentially isolated from the coil structure. Thus, charged particles are directed along magnetic field lines to the direct energy converter without appreciable losses. A direct energy converter unit designed to be compatible to this unique system is also described. It basically consists of a separator and a traveling wave converter. A ...
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 108 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 1011?v.g.), and complete tumor regression w...
Examination of measurement invariance provides a powerful method to evaluate the hypothesis that the same set of psychological constructs underlies a set of test scores in different populations. If measurement invariance is observed, then the same psychological meaning can be ascribed to scores in both populations. In this study, the measurement model including core and supplementary subtests of the Wechsler Adult Intelligence Scale-Fourth edition (WAIS-IV) were compared across the U.S. and Canadian standardization samples. Populations were compared on the 15 subtest version of the test in people aged 70 and younger and on the 12 subtest version in people aged 70 or older. Results indicated that a slightly modified version of the four-factor model reported in the WAIS-IV technical manual provided the best fit in both populations and in both age groups. The null hypothesis of measurement invariance across populations was not rejected, and the results provide direct ...
Using the SCUBA bolometer array on the JCMT, we have carried out a submillimetre survey of Broad Absorption Line quasars (BALQs). The sample has been chosen to match, in redshift and optical luminosity, an existing benchmark 850um sample of radio-quiet quasars, allowing a direct comparison of the submm properties of BAL quasars relative to the parent radio-quiet population. We reach a submm limit 1.5mJy at 850um, allowing a more rigorous measure of the submm properties of BAL quasars than previous studies. Our submm photometry complements extensive observations at other wavelengths, in particular X-rays with Chandra and mid-infrared with Spitzer. To compare the 850um flux distribution of BALQs with that of the non-BAL quasar benchmark sample, we employ a suite of statistical methods, including survival analysis and a novel Bayesian derivation of the underlying flux distribution. Although there are no strong grounds for rejecting the null hypothesis that BALQs on ...
Abstract Unrefined and refined black raspberry seed oils (RSOs) were examined for their lipid-modulating effects in male Syrian hamsters fed high-cholesterol (0.12% g/g), high-fat (9% g/g) diets. Hamsters fed the refined and the unrefined RSO diets had equivalently lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol in comparison with the atherogenic coconut oil diet. The unrefined RSO treatment group did not differ in liver total and esterified cholesterol from the coconut oil-fed control animals, but the refined RSO resulted in significantly elevated liver total and esterified cholesterol concentrations. The unrefined RSO diets significantly lowered plasma triglycerides (46%; P=.0126) in comparison with the coconut oil diet, whereas the refined RSO only tended to lower plasma triglyceride (29%; P=.1630). Liver triglyceride concentrations were lower in the unrefined (46%; P=.0002) and refined (36%; P=.0005) RSO-fed animals than the coconut oil group, with the ...
A study was undertaken to examine the uptake, distribution, and interaction of five activation products (Co-57, Be-7, Cs-134, Rb-83, and Mn-54) within the biotic and abiotic components surrounding the waste treatment lagoons of the Los Alamos Meson Physics Facility (LAMPF). The study attempted to ascertain where, and what specific interactions were taking place among the isotopes and the biotic/abiotic components. A statistical approach, utilizing Multivariate Analysis of Variance (MANOVA), was conducted testing the radioisotopic concentrations by (1) the trophic levels (TROPLVL) in each position sampled on the grid, (2) where sampled on the grid (TRAN), (3) where sampled with-in each grid line (PLOT), and (4) the side with which sampled (SIDE). This provided both the dependent and independent variables that would be tested. The Null Hypothesis (Ho) tested the difference in the mean values of the isotopes within/between each of the four independent variables. The ...
A study was undertaken to examine the uptake, distribution, and interaction of five activation products (Co-57, Be-7, Cs-134, Rb-83, and Mn-54) within the biotic and abiotic components surrounding the waste treatment lagoons of the Los Alamos Meson Physics Facility (LAMPF). The study attempted to ascertain where, and what specific interactions were taking place among the isotopes and the biotic/abiotic components. A statistical approach, utilizing Multivariate Analysis of Variance (MANOVA), was conducted testing the radioisotopic concentrations by (1) the trophic levels (TROPLVL) in each position sampled on the grid, (2) where sampled on the grid (TRAN), (3) where sampled with-in each grid line (PLOT), and (4) the side with which sampled (SIDE). This provided both the dependent and independent variables that would be tested. The Null Hypothesis (Ho) tested the difference in the mean values of the isotopes within/between each of the four independent variables. The ...
The single-axis portion of a three-axis superconducting gravity gradiometer has been completed in the course of this research. The theory of the superconducting gravity gradiometer has been generalized and put into a Lagrangian formulation. A condition for frequency-independent common mode balance combined with a multi-stage vibration isolation scheme has enabled a stable operation of the gradiometer for prolonged periods. In a preliminary test, the gradiometer has exhibited a noise level of 1-2 E Hz"-/sup 1/2/ below 1 Hz, limited by seismic noise, where 1 E = 10"-"9 m s"-"2 m"-"1. To perform a test of the inverse square law, the single-axis gradiometer is mounted with its axis tilted from the vertial by an angle tan"-"1 #sq root#2. The device is then turned incrementally by 120"0 around the vertical to carry the gradiometer from one axis to the other two axes of an orthogonal coordinate system. A lead pendulum weighing 1600 kg forms a periodic monopole source of gravity. The ...
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 10(8) plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 10(11) v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 x 10(9) PFU) of rAdv-hTERTC27 significantly augmented the ...