spl(2,1) dynamical supersymmetry and suppression of ferromagnetism in flat band double-exchange models

The low energy spectrum of the ferromagnetic Kondo lattice model on a N-site complete graph extended with on-site repulsion is obtained from the underlying spl(2,1) algebra properties in the strong coupling limit. The ferromagnetic ground state is realized for 1 and N+1 electrons only. We identify the large density of states to be responsible for the suppression of the ferromagnetic state and argue that a similar situation is encountered in the Kagome, pyrochlore, and other lattices with flat bands in their one-particle density of states.Comment: 7 pages, 1 figur

Analysis of Patients Visiting Niigata University Medical and Dental Hospital with Chief Complaints of Metal Allergy And/or Focal Infection in the Previous 8 Years

Dental metal allergy and dental focal infection are possible causes of dermatological diseases, but have been the subjects of few reports to date. We have been treating such patients in our special clinic for more than 20 years.The purpose of the present study was to investigate the mouths of patients visiting our dental hospital over an 8-year period, with the aim of clarifying whether dental metal allergy and/or dental focal infection affects their dermatologic conditions.We surveyed all clinical records of the 185 patients who visited Niigata University Medical and Dental Hospital with chief complaints of dental metal allergy since 2002. Diagnostics of skin diseases, periodontal records, periapical lesions, dental caries, dental metal series patch test results and Electron Probed Micro-Analysis (EPMA) data were investigated. Ninety-two (49%) patients were suffering from pustulosis palmaris et plantaris and 20 (11%) patients had lichen planus. Eighty-two (49%) patients showed positive reactions on patch testing. Based on the result of patch tests, Ni showed the highest positivity rate (62%, 51 patients), but on EPMA, the number of patients with Ni as an allergen was 14 (27%). On the other hand, more than 98% of patients who showed positive reactions on patch test to Pd and Au had these metals in their dental prostheses. In addition, 112 (60%) patients showed the possibility of dental focal infection

Series-Parallel and Parallel Identification Schemes for a Class of Continuous Nonlinear Systems

Fig. 4(a) shows the parameter estimates under the existence of the measmable disturbance (di = 5, a\ = 0) with the parameter estimates under the ideal condition (di = a\ = 0) overlaid. Since the inserted DDR's remove the disturbance from the inputoutput relation, the disturbance does not slow down the identification speed. Fig. 4(6) shows the parameter estimates under the existence of the unmeasurable disturbance (di = 0, d 2 = 1) with the parameter estimates under the ideal condition (di = di = 0) overlaid. There exists no difference between the two cases as far as the identification speed is concerned. In the simulation, the step disturbances, di and d 2 , were injected to the plant at k = 0. Thus, strictly speaking, at k = 0, di(k) and d 2 (fc) did not satisfy equation V Conclusions Adverse effects of deterministic disturbances in linear identification have been pointed out, and a method to remove such effects has been presented. This method works for measurable and unmeasurable disturbances which can be regarded as the outputs of free systems with known dynamics. The unmeasurable disturbance must always be removed to achieve successful identification. When the disturbance is measurable, however, it does not have to be removed if it can provide a positive contribution to identification. A constant disturbance was shown to slow down the identification speed. The best results will be obtained if one selects a DDR which removes only undesirable disturbances. In this technical brief, discrete series-parallel and parallel identification schemes for single-input, single-output systems were considered. The same principle, however, can be extended to other situations including the continuous time case and multi-input, and multi-output case. References 1 Astrom, K. J., and Eykhoff, P., "System Identification -A Survey," Automatica, Vol. 7, 1971, pp. 123-16

Refined human artificial chromosome vectors for gene therapy and animal transgenesis

Human artificial chromosomes (HACs) have several advantages as gene therapy vectors, including stable episomal maintenance, and the ability to carry large gene inserts. We previously developed HAC vectors from the normal human chromosomes using a chromosome engineering technique. However, endogenous genes were remained in these HACs, limiting their therapeutic applications. In this study, we refined a HAC vector without endogenous genes from human chromosome 21 in homologous recombination-proficient chicken DT40 cells. The HAC was physically characterized using a transformation-associated recombination (TAR) cloning strategy followed by sequencing of TAR-bacterial artificial chromosome clones. No endogenous genes were remained in the HAC. We demonstrated that any desired gene can be cloned into the HAC using the Cre-loxP system in Chinese hamster ovary cells, or a homologous recombination system in DT40 cells. The HAC can be efficiently transferred to other type of cells including mouse ES cells via microcell-mediated chromosome transfer. The transferred HAC was stably maintained in vitro and in vivo. Furthermore, tumor cells containing a HAC carrying the suicide gene, herpes simplex virus thymidine kinase (HSV-TK), were selectively killed by ganciclovir in vitro and in vivo. Thus, this novel HAC vector may be useful not only for gene and cell therapy, but also for animal transgenesis

Human RSPO1/R-spondin1 Is Expressed during Early Ovary Development and Augments β-Catenin Signaling

Human testis development starts from around 42 days post conception with a transient wave of SRY expression followed by up-regulation of testis specific genes and a distinct set of morphological, paracrine and endocrine events. Although anatomical changes in the ovary are less marked, a distinct sub-set of ovary specific genes are also expressed during this time. The furin-domain containing peptide R-spondin1 (RSPO1) has recently emerged as an important regulator of ovary development through up-regulation of the WNT/β-catenin pathway to oppose testis formation. Here, we show that RSPO1 is upregulated in the ovary but not in the testis during critical early stages of gonad development in humans (between 6–9 weeks post conception), whereas the expression of the related genes WNT4 and CTNNB1 (encoding β catenin) is not significantly different between these tissues. Furthermore, reduced R-spondin1 function in the ovotestis of an individual (46,XX) with a RSPO1 mutation leads to reduced β-catenin protein and WNT4 mRNA levels, consistent with down regulation of ovarian pathways. Transfection of wild-type RSPO1 cDNA resulted in weak dose-dependent activation of a β-catenin responsive TOPFLASH reporter (1.8 fold maximum), whereas co-transfection of CTNNB1 (encoding β-catenin) with RSPO1 resulted in dose-dependent synergistic augmentation of this reporter (approximately 10 fold). Furthermore, R-spondin1 showed strong nuclear localization in several different cell lines. Taken together, these data show that R-spondin1 is upregulated during critical stages of early human ovary development and may function as a tissue-specific amplifier of β-catenin signaling to oppose testis determination

Transplantation directs oocyte maturation from embryonic stem cells and provides a therapeutic strategy for female infertility

Ten to 15% of couples are infertile, with the most common causes being linked to the production of few or no oocytes or sperm. Yet, our understanding of human germ cell development is poor, at least in part due to the inaccessibility of early stages to genetic and developmental studies. Embryonic stem cells (ESCs) provide an in vitro system to study oocyte development and potentially treat female infertility. However, most studies of ESC differentiation to oocytes have not documented fundamental properties of endogenous development, making it difficult to determine the physiologic relevance of differentiated germ cells. Here, we sought to establish fundamental parameters of oocyte development during ESC differentiation to explore suitability for basic developmental genetic applications using the mouse as a model prior to translating to the human system. We demonstrate a timeline of definitive germ cell differentiation from ESCs in vitro that initially parallels endogenous oocyte development in vivo by single-cell expression profiling and analysis of functional milestones including responsiveness to defined maturation media, shared genetic requirement of Dazl, and entry into meiosis. However, ESC-derived oocyte maturation ultimately fails in vitro. To overcome this obstacle, we transplant ESC-derived oocytes into an ovarian niche to direct their functional maturation and, thereby, present rigorous evidence of oocyte physiologic relevance and a potential therapeutic strategy for infertility

Mammalian sex determination—insights from humans and mice

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research