Cohomology of toric line bundles via simplicial Alexander duality

We give a rigorous mathematical proof for the validity of the toric sheaf cohomology algorithm conjectured in the recent paper by R. Blumenhagen, B. Jurke, T. Rahn, and H. Roschy (arXiv:1003.5217). We actually prove not only the original algorithm but also a speed-up version of it. Our proof is independent from (in fact appeared earlier on the arXiv than) the proof by H. Roschy and T. Rahn (arXiv:1006.2392), and has several advantages such as being shorter and cleaner and can also settle the additional conjecture on "Serre duality for Betti numbers" which was raised but unresolved in arXiv:1006.2392.Comment: 9 pages. Theorem 1.1 and Corollary 1.2 improved; Abstract and Introduction modified; References updated. To appear in Journal of Mathematical Physic

Evaluation of severe accident risks, Peach Bottom, Unit 2: Main report

In support of the Nuclear Regulatory Commission's (NRC's) assessment of the risk from severe accidents at commercial nuclear power plants in the US reported NUREG-1150, the Severe Accident Risk Reduction Program (SARRP) has completed a revised calculation of the risk to the general public from severe accidents at the Peach Bottom Atomic Power Station, Unit 2. This power plant, located in southeastern Pennsylvania, is operated by the Philadelphia Electric Company. The emphasis in this risk analysis was not on determining a so-called'' point estimate of risk. Rather, it was to determine the distribution of risk, and to discover the uncertainties that account for the breadth of this distribution. Off-site risk initiated by events both internal and external to the power station were assessed. 39 refs., 174 figs., 133 tabs

Increased site-specific phosphorylation of tyrosine hydroxylase accompanies stimulation of enzymatic activity induced by cessation of dopamine neuronal activity. Mol Pharmacol

ABSTRACT Activation of striatal dopamine (DA) neurons by neuroleptic treatment or by electrical stimulation of the nigrostriatal pathway increases the activity of tyrosine hydroxylase (TH). The increase is mediated by phosphorylation of the enzyme. However, abolition of DA neuronal activity [by ␥-butyrolactone (GBL) treatment or transection of the nigrostriatal pathway] also increases TH activity. Quantitative blot immunolabeling experiments using site-and phosphorylation state-specific antibodies to TH demonstrated that GBL treatment (750 mg/kg, 35 min) significantly increased phosphorylation at Ser19 (ϩ40%) and Ser40 (ϩ217%) without altering Ser31 phosphorylation. Concomitantly, GBL treatment [along with the 3,4-dihydroxyphenylalanine (dopa) decarboxylase inhibitor NSD-1015, 100 mg/ kg, 30 min] increased in vivo striatal dopa accumulation and in vitro TH activity 3-fold. Likewise, cerebral hemitransection of the nigrostriatal pathway significantly increased phosphorylation of TH at Ser19 (ϩ89%) and Ser40 (ϩ158%) but not at Ser31; dopa levels were increased accordingly (ϩ191%). Kinetic analysis of TH activity established that GBL treatment and hemitransection primarily decreased the K m for the cofactor tetrahydrobiopterin (3-fold). The effects of GBL and hemitransection were abolished or attenuated by pretreatment with the DA agonist R-(Ϫ)-N-n-propylnorapomorphine (NPA; 30 g/ kg, 40 min), presumably via stimulation of inhibitory presynaptic DA autoreceptors. NPA dose-response curves for reversal of GBL-induced dopa accumulation and Ser40 phosphorylation were identical; however, only the highest dose of NPA reversed the small and variable increase in Ser19 phosphorylation. Thus, TH activity seems to be regulated by phosphorylation in both hyper-and hypoactive striatal DA neurons; in the latter case, activation seems to be caused by selective phosphorylation of Ser40. It is now well established that short-term regulation of tyrosine hydroxylase (TH) is accomplished by dynamic changes in the phosphorylation state of the enzyme Electrical stimulation of the medial forebrain bundle (containing the dopaminergic afferents to the forebrain) is known to elicit activation of striatal T

Data incongruence and the problem of avian louse phylogeny

Recent studies based on different types of data (i.e. morphological and molecular) have supported conflicting phylogenies for the genera of avian feather lice (Ischnocera: Phthiraptera). We analyse new and published data from morphology and from mitochondrial (12S rRNA and COI) and nuclear (EF1-) genes to explore the sources of this incongruence and explain these conflicts. Character convergence, multiple substitutions at high divergences, and ancient radiation over a short period of time have contributed to the problem of resolving louse phylogeny with the data currently available. We show that apparent incongruence between the molecular datasets is largely attributable to rate variation and nonstationarity of base composition. In contrast, highly significant character incongruence leads to topological incongruence between the molecular and morphological data. We consider ways in which biases in the sequence data could be misleading, using several maximum likelihood models and LogDet corrections. The hierarchical structure of the data is explored using likelihood mapping and SplitsTree methods. Ultimately, we concede there is strong discordance between the molecular and morphological data and apply the conditional combination approach in this case. We conclude that higher level phylogenetic relationships within avian Ischnocera remain extremely problematic. However, consensus between datasets is beginning to converge on a stable phylogeny for avian lice, at and below the familial rank

Expression Pattern of Kv11 (Ether à-go-go-Related Gene; erg) K+ Channels in the Mouse Retina

In response to light, most retinal neurons exhibit gradual changes in membrane potential. Therefore K+ channels that mediate threshold currents are well-suited for the fine-tuning of signal transduction. In the present study we demonstrate the expression of the different Kv11 (ether-à-go-go related gene; erg) channel subunits in the human and mouse retina by RT PCR and quantitative PCR, respectively. Immunofluorescence analysis with cryosections of mouse retinae revealed the following local distribution of the three Kv11 subunits: Kv11.1 (m-erg1) displayed the most abundant expression with the strongest immunoreactivity in rod bipolar cells. In addition, immunoreactivity was found in the inner part of the outer plexiform layer (OPL), in the inner plexiform layer (IPL) and in the inner segments of photoreceptors. Immunoreactivity for Kv11.2 (m-erg2) was observed in the outer part of the OPL and throughout the IPL. Double-labeling for vGluT1 or synaptophysin indicated a mainly presynaptic localization of Kv11.2. While no significant staining for Kv11.3 (m-erg3) was detected in the neuronal retina, strong Kv11.3 immunoreactivity was present in the apical membrane of the retinal pigment epithelium. The different expression levels were confirmed by real-time PCR showing almost equal levels of Kv11.1 and Kv11.2, while Kv11.3 mRNA expression was significantly lower. The two main splice variants of Kv11.1, isoforms a and b were detected in comparable levels suggesting a possible formation of cGMP/cGK-sensitive Kv11.1 channels in photoreceptors and rod bipolar cells. Taken together, the immunohistological results revealed different expression patterns of the three Kv11 channels in the mouse retina supposing distinct physiological roles

Long term effects of micro-surgical testicular sperm extraction on androgen status in patients with non obstructive azoospermia

BACKGROUND: The aim of our study was to review the results of microsurgically performed testicular sperm extraction (TESE) and to evaluate its possible long term effects on serum testosterone (T). METHODS: We operated on 48 men (35 +/- 8 years) with non-obstructive azoospermia (NOA). If no spermatozoa were found following a micro epididymal sperm extraction (Silber et al., 1994) and testicular biopsy, testicular microdissection was performed or multiple microsurgical testicular biopsies were taken. The mean follow-up of the serum T was 2.4 +/- 1.1 years. RESULTS: Sperm was retrieved in 17/48 (35%) of the men. The per couple take home baby rate if sperm was retrieved was 4/17 (24%). Serum T decreased significantly at follow-up (p < 0.05) and 5/31 (16%) de novo androgen deficiencies developed CONCLUSION: In patients with non-obstructive azoospermia in whom no spermatozoa were found following a micro epididymal sperm aspiration and a simple testicular biopsy, we were able to retrieve spermatozoa in 35% of the men. The take home baby rate was 24% among couples with spermatozoa present upon TESE. De novo androgen deficiency occurred in 16% of the male patients following TESE indicating that, in men with NOA, long term hormonal follow up is recommended after TESE

Potential pitfalls of modelling ribosomal RNA data in phylogenetic tree reconstruction: Evidence from case studies in the Metazoa

<p>Abstract</p> <p>Background</p> <p>Failure to account for covariation patterns in helical regions of ribosomal RNA (rRNA) genes has the potential to misdirect the estimation of the phylogenetic signal of the data. Furthermore, the extremes of length variation among taxa, combined with regional substitution rate variation can mislead the alignment of rRNA sequences and thus distort subsequent tree reconstructions. However, recent developments in phylogenetic methodology now allow a comprehensive integration of secondary structures in alignment and tree reconstruction analyses based on rRNA sequences, which has been shown to correct some of these problems. Here, we explore the potentials of RNA substitution models and the interactions of specific model setups with the inherent pattern of covariation in rRNA stems and substitution rate variation among loop regions.</p> <p>Results</p> <p>We found an explicit impact of RNA substitution models on tree reconstruction analyses. The application of specific RNA models in tree reconstructions is hampered by interaction between the appropriate modelling of covarying sites in stem regions, and excessive homoplasy in some loop regions. RNA models often failed to recover reasonable trees when single-stranded regions are excessively homoplastic, because these regions contribute a greater proportion of the data when covarying sites are essentially downweighted. In this context, the RNA6A model outperformed all other models, including the more parametrized RNA7 and RNA16 models.</p> <p>Conclusions</p> <p>Our results depict a trade-off between increased accuracy in estimation of interdependencies in helical regions with the risk of magnifying positions lacking phylogenetic signal. We can therefore conclude that caution is warranted when applying rRNA covariation models, and suggest that loop regions be independently screened for phylogenetic signal, and eliminated when they are indistinguishable from random noise. In addition to covariation and homoplasy, other factors, like non-stationarity of substitution rates and base compositional heterogeneity, can disrupt the signal of ribosomal RNA data. All these factors dictate sophisticated estimation of evolutionary pattern in rRNA data, just as other molecular data require similarly complicated (but different) corrections.</p

Magnetic resonance imaging of anterior cruciate ligament rupture

BACKGROUND: Magnetic resonance (MR) imaging is a useful diagnostic tool for the assessment of knee joint injury. Anterior cruciate ligament repair is a commonly performed orthopaedic procedure. This paper examines the concordance between MR imaging and arthroscopic findings. METHODS: Between February, 1996 and February, 1998, 48 patients who underwent magnetic resonance (MR) imaging of the knee were reported to have complete tears of the anterior cruciate ligament (ACL). Of the 48 patients, 36 were male, and 12 female. The average age was 27 years (range: 15 to 45). Operative reconstruction using a patellar bone-tendon-bone autograft was arranged for each patient, and an arthroscopic examination was performed to confirm the diagnosis immediately prior to reconstructive surgery. RESULTS: In 16 of the 48 patients, reconstructive surgery was cancelled when incomplete lesions were noted during arthroscopy, making reconstructive surgery unnecessary. The remaining 32 patients were found to have complete tears of the ACL, and therefore underwent reconstructive surgery. Using arthroscopy as an independent, reliable reference standard for ACL tear diagnosis, the reliability of MR imaging was evaluated. The true positive rate for complete ACL tear diagnosis with MR imaging was 67%, making the possibility of a false-positive report of "complete ACL tear" inevitable with MR imaging. CONCLUSIONS: Since conservative treatment is sufficient for incomplete ACL tears, the decision to undertake ACL reconstruction should not be based on MR findings alone

Pre-Clinical Evaluation of a Replication-Competent Recombinant Adenovirus Serotype 4 Vaccine Expressing Influenza H5 Hemagglutinin

Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis.The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus.Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine