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Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

The National Institute of Information and Communications Technology (NICT) has developed a Sr optical lattice clock and optical ion clocks employing In+and Ca+. The centimeter-level uncertainty of site elevation is the cause of 10^(-18)-level frequency uncertainties of optical frequency standards. It is significantly important to understand frequency changes caused by solid-earth tides that often range from 10 to 20 cm in amplitude, by oceanic tidal loading, crustal deformations due to earthquakes, and ground movements with groundwater changes for the stable operation of optical atomic clocks.NICT and partners including the Geospatial Information Authority of Japan (GSI) have been jointly conducting leveling surveys and relative gravimeter observations at NICT’s headquarters in Koganei. These observations reduce the contribution of gravitational redshift to the total uncertainty of the optical lattice clock to the 10^(-19)level. With the support of National Institute of Polar Research (NIPR), absolute gravity measurements were performed in August 2019 and May 2022 to evaluate the effects of the 2011 off the Pacific coast of Tohoku Earthquake on postseismic crustal movement. The obtained absolute gravity change between the two periods was -43.8 μGal, which matches the trend of GNSS vertical movement obtained by GSI. We have introduced a Micro-g LaCoste’s gPhoneX gravimeter for continuous gravity measurements nearby the optical clocks in the end of 2021 and have started to investigate the temporal variation of the ground water level in Koganei. We will present preliminary results of these geodetic measurements., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Competing Risk Analysis (CRA) aims at the correct estimation of the marginal probability of occurrence of an event in the presence of competing events. Many of the statistical approaches developed for CRA are limited by strong assumptions about the underlying stochastic processes. To overcome these issues and to handle censoring, machine learning approaches for CRA have designed specialized cost functions. However, these approaches are not generalizable, and are computationally expensive. This paper formulates CRA as a cause-specific regression problem and proposes DeepPseudo models, which use simple and effective feed-forward deep neural networks, to predict the cumulative incidence function (CIF) using Aalen-Johansen estimator-based pseudo values. DeepPseudo models capture the time-varying covariate effect on CIF while handling the censored observations. We show how DeepPseudo models can address co-variate dependent censoring by using modified pseudo values. Experiments on real and synthetic datasets demonstrate that our proposed models obtain promising and statistically significant results compared to the state-of-the-art CRA approaches. Furthermore, we show that explainable methods such as Layer-wise Relevance Propagation can be used to interpret the predictions of our DeepPseudo models.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. Genome analysis on MAH of human isolates has been proceeding, however, those of pigs are limited despite its potential source of infection to human. In the current study, we obtained 30 draft genome sequences of MAH of pigs reared in Japan. The 30 draft genomes consisted of 4,848,678 – 5,620,788 bp length, 4,652 – 5,388 coding genes and 46 – 75 (Med: 47) tRNAs. All isolates had restriction modification associated genes and 185 – 222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.

Magnetic reconnection is a process whereby magnetic field lines in different directions "reconnect" with each other, resulting in the rearrangement of magnetic field topology together with the conversion of magnetic field energy into the kinetic energy (K.E.) of energetic particles. This process occurs in magnetized astronomical plasmas, such as those in the solar corona, Earth's magnetosphere, and active galactic nuclei, and accounts for various phenomena, such as solar flares, energetic particle acceleration, and powering of photon emission. In the present study, we report the experimental demonstration of magnetic reconnection under relativistic electron magnetization situation, along with the observation of power-law distributed outflow in both electron and proton energy spectra. Through irradiation of an intense laser on a "micro-coil", relativistically magnetized plasma was produced and magnetic reconnection was performed with maximum magnetic field 3 kT. In the downstream outflow direction, the non-thermal component is observed in the high-energy part of both electron and proton spectra, with a significantly harder power-law slope of the electron spectrum (p = 1.535 +/- 0.015) that is similar to the electron injection model proposed to explain a hard emission tail of Cygnus X-1, a galactic X-ray source with the same order of magnetization. The obtained result showed experimentally that the magnetization condition in the emitting region of a galactic X-ray source is sufficient to build a hard electron population through magnetic reconnection., Comment: 25 pages, 10 figures

Many Thai females feel that their facial skin is oily and suffer from acne. Previously we have confirmed that a facial cleanser formulated with alkyl ether carboxylate (AEC) and alkyl carboxylate (AC) effectively removed sebum and decreased acne prompt without inducing dry skin on Japanese male subjects. In this study, we evaluated the efficacy of this formulated facial cleanser on Thai female subjects with moderate or mild grade acne in Bangkok, Thailand. We designed a controlled clinical trial. Sixteen female subjects used AEC/AC formulated cleanser twice a day after discontinuing their currently using facial cleansers. Assessment of the efficacy was conducted prior to the start of the study, and at the end of weeks 2 and 4. Following usage of this cleanser for 4 weeks, sebum secretion levels on the forehead skin significantly decreased. Corresponding to decrease in facial sebum, 10 subjects had decrease in non-inflammatory acne. Furthermore eight subjects decreased in inflammatory acne, and the decreases in the number of inflammatory acne within 4 weeks were statistically significant. These decreases in sebum and acne prompt were recognized by subjects. Despite the sebum were cleansed well, the cutaneous capacitance increased significantly within 4 weeks, and there were no complaints of dryness or irritation of the skin during the study. From these results, we conclude that washing the face with cleanser formulated with AEC and AC is effective for acne care in Thai females

PurposeSurvival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype.MethodsUsing pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes.ResultsHistory of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94.ConclusionsHistories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639 rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous =1.19, 95% CI 1.02-1.38, p=0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous =0.51, 95% CI 0.39-0.67, p=1.10x10(-6) ) and MORC4-rs 12837024 (ORhomozygous =2.07 (1.55-2.77, ptrend =0.7x10(-11) ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639 rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants. This article is protected by copyright. All rights reserved.

Electron acceleration by relativistically intense laser beam propagating along a curved surface allows to split softly the accelerated electron bunch and the laser beam. The presence of a curved surface allows to switch an adiabatic invariant of electrons in the wave instantly leaving the gained energy to the particles. The efficient acceleration is provided by the presence of strong transient quasistationary fields in the interaction region and a long efficient acceleration length. The curvature of the surface allows to select the accelerated particles and provides their narrow angular distribution. The mechanism at work is explicitly demonstrated in theoretical models and experiments.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. We conducted a fine-mapping study across 2.06 Mb (chr8:127,561,724 -129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium. We found three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional P = 5.8 × 10-6), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional P = 1.1 × 10-6), and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional P = 1.1 × 10-4). Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas, and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r2 = 0.77), were putatively functional variants for two of the five independent association signals. Our results highlight multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry

Background: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis. ispartof: Human Molecular Genetics vol:24 issue:10 pages:2966-84 ispartof: location:England status: published

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to\ud the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and\ud a modest reduction in risk of breast cancer in women age ≤50 years.\ud Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of\ud 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping\ud of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine\ud whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.\ud Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found\ud no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were\ud OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was\ud no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche\ud in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast\ud cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a\ud reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94;\ud ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06,\ud 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29).\ud Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both\ud breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche\ud and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 x 10 26], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 x 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 x 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 x 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 x 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

A novel uracil-DNA degrading protein factor (termed UDE) was identified in Drosophila melanogaster with no significant structural and functional homology to other uracil-DNA binding or processing factors. Determination of the 3D structure of UDE will be a true breakthrough in description of the molecular mechanism of action of UDE catalysis, as well as in general uracil-recognition and nuclease action. The revolutionary ESPRIT technology was applied to the novel protein UDE to overcome problems in identifying soluble expressing constructs given the absence of precise information on domain content and arrangement. Nine specimen from the created numerous truncated constructs of UDE were choosen to dechiper structural and functional relationships. VUVCD with neural network was performed to define the secondary structure content and location of UDE and its truncated variants. The quantitative analysis demonstrated exclusive {\alpha}-helical content for the full-length protein, which is preserved in the truncated constructs. Partition of {\alpha}-helical boundles comparison with the truncated protein segments denoted new domain boundaries which differ from the conserved motifs determined by sequence-based alignment of UDE homologues in pupating insects. Here we demonstrate that combination of ESPRIT and VUVCD with NN provided significant structural description of UDE and resulted useful truncated constructs for further detailed functional studies.

Journal article Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10!¿8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. European Community Seventh Framework Programme - grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) peer-reviewed

To obtain the basic data on the route of Giardia infection as zoonosis, of many regions in Japan, the feces from 2218 dogs were examined for detection of Giardia cysts. Giardia cysts were detected in 239 of the 2218 dogs (10.9%), which was the same as previous reports from America. None were found from the owners of 51 dogs in which Giardia cysts were detected. The detection rates of each facilities were, 68 of 366 (18.6%) from the breeder's kennels, 169 of 1811 (9.3%) in individual houses, 2 of 42 (4.9%) from research institutes. The detection rate of the breeder's kennels was higher than the other two facilities (p less than 0.05, p less than 0.001). The detection rates of Kanagawa and Shizuoka prefectures among 17 regions in Japan were higher than the others (p less than 0.001, p less than 0.05). Especially in Shizuoka, the rate of the individual houses was higher than from breeder's kennels. In kanagawa the rates of the individual houses and the breeders kennels were higher than the mean in Japan (p less than 0.001). Therefore one must instruct the breeders when teaching health education to included zoonosis, and that the detection rate of the age groups of less than 3 years old was high-221 of 1276 (17.3%). Since the detection rates of Giardia cysts in the dogs were low, the possibility that human infection acquired from dogs was low. However, some of patients with giardiasis we encountered had never been abroad, and it is not yet clear whether Giardia is strictly host specific or not, so attention should be paid to the possibility of cross-infection between man and animals.

This paper analyzes the behavior of coating particles as well as the gas flow in a High-Velocity Oxy-Fuel (HVOF) gun by using numerical simulation. Special attention is paid to the particle behavior in turbulent boundary-layer inside the barrel.

Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.

OBJECTIVE. The value of preoperative transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been duly appreciated. The authors assessed the advantages and disadvantages of preoperative TACE by reviewing their experience with the procedure. METHODS. A total of 140 patients who underwent hepatectomy for HCC were entered into the study (105 received preoperative TACE and 35 did not). The authors investigated the reduction of tumor size and the complications after TACE, as well as the relationship between the interval from TACE to resection and the occurrence of complications. They compared postoperative morbidity and mortality between the TACE and non-TACE groups. They also compared survival and disease-free survival between the two groups, as well as between subgroups, defined by the extent of tumor necrosis achieved with TACE. RESULTS. A distinct reduction of tumor size was observed in approximately half of the TACE group. However, there were 68 appreciable complications of TACE in 56 patients (53.3%), and the interval between TACE and resection was significantly prolonged in the patients with complications. The postoperative morbidity and mortality rates of the TACE group were not different from those of the non-TACE group. Preoperative TACE did not improve the survival or disease-free survival of the whole patient group after hepatectomy. In addition, the survival and disease-free survival rates of the three TACE subgroups were not different from those of the non-TACE group. CONCLUSIONS. Preoperative TACE should only be performed to reduce tumor bulk in patients with HCC with borderline resectability. In such patients, increased tumor resectability appears to improve the survival rate. Preoperative TACE does not promote tumor recurrence.

Specific-pathogen-free (SPF) ducks that were 1, 3, 4, 7, 10, 30, and 180 days old were inoculated experimentally orally or nasally with infectious bursal disease virus (IBDV). Attempts to induce clinical disease in ducks with strain J1 or FK-78 of IBDV were unsuccessful. Virus-recovery attempts from organ and intestinal contents were also unsuccessful. No significant gross or histopathological lesions were found in liver, spleen, kidney, heart, or bursa of Fabricius of 1- and 3-day-old ducks at 4 or 7 days postinoculation. The ratios of bursa weight to body weight of 1-, 10-, and 30-day-old inoculated and control ducks revealed no difference at 21 days postinoculation. The ducks responded serologically, however, by developing both virus-neutralizing and agar-gel-precipitin antibodies. Virus multiplied in embryonated duck eggs and duck embryo fibroblast cells but not in duck kidney cells.

A new, simple, and specific screening method for Ca-entry blockers is reported. In the presence of various blockers of Ca-entry (Ca-channel blockers), Ca 2+ (1 × 10 −4 M) causes Ca reversal, i.e., it causes relaxation of rat uterine smooth muscle that has been tonically contracted with oxytocin in Ca-free medium (Cafree contraction) after prolonged preincubation with 3 mM EGTA. The potencies of various drugs to cause Ca reversal, assessed on an all-or-none basis, were found to reflect their activities of blocking Ca entry. The potencies of drugs for blocking Ca entry via voltage-operated Ca-channels could be determined in 125.6 mM K + Ca-free medium. Drugs that inhibited Ca-free contraction directly have some other antispasmodic activity. Conventionally, activity for blocking Ca entry is screened by measuring inhibition of Ca-induced contraction, but true Ca-entry blocking activity cannot be differentiated clearly from other antispasmodic activity when a drug has both activities. However, by measuring Ca reversal, activity for blocking Ca entry only can easily be found, when done in solution with high K + content for blocking voltage-operated channels and when done in solution with normal K + content for blocking voltage-independent channels.

Tumor lymphocyte infiltration has been associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied invasive breast cancer patients of European ancestry with stage I-III disease, including 9,334 ER-positive patients (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy).

The retention behavior of polymers having the specific affinities of glyco-hydrolases for pulp fibers was investigated with regard to paper-strength enhancement in contaminated papermaking systems. Carbohydrate-binding modules (CBMs) of cellulases derived from Trichoderma viride and T. reesei, and of xylanase from Thermomyces lanuginosus, were obtained by site-directed digestion with papain, then introduced into anionic polyacrylamide (A-PAM) via a peptide condensation reaction. Three types of CBM-conjugated A-PAMs (CBM-A-PAMs) displayed different retention behavior, depending on the kind of pulp substrates, i.e. hardwood and softwood fibers. The CBM-A-PAM from T. viride demonstrated good additive retention for hardwood pulp fibers, resulting in high tensile strength of paper sheets, even under contaminated conditions in the presence of Ca2+ ions and ligninsulfonate. The CBM-A-PAM from T. reesei showed better performance for softwood than for hardwood sheets. The xylanase CBM-A-PAM was preferentially retained on hardwood fibers in which hemicelluloses might be present. Such an additive retention system, with inherent affinities of enzymes for pulp fibers, is expected to expand the application range of CBM-polymers in practical wet-end processes.