Birational geometry of hypersurfaces in products of projective spaces

We study the birational properties of hypersurfaces in products of projective spaces. In the case of hypersurfaces in Pm x Pn, we describe their nef, movable and e ective cones and determine when they are Mori dream spaces. Using this, we give new simple examples of non-Mori dream spaces and analogues of Mumford's example of a strictly nef line bundle which is not ample.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00209-015-1415-

A Global SU(5) F-theory model with Wilson line breaking

We engineer compact SU(5) Grand Unified Theories in F-theory in which GUT-breaking is achieved by a discrete Wilson line. Because the internal gauge field is flat, these models avoid the high scale threshold corrections associated with hypercharge flux. Along the way, we exemplify the `local-to-global' approach in F-theory model building and demonstrate how the Tate divisor formalism can be used to address several challenges of extending local models to global ones. These include in particular the construction of G-fluxes that extend non-inherited bundles and the engineering of U(1) symmetries. We go beyond chirality computations and determine the precise (charged) massless spectrum, finding exactly three families of quarks and leptons but excessive doublet and/or triplet pairs in the Higgs sector (depending on the example) and vector-like exotics descending from the adjoint of SU(5)_{GUT}. Understanding why vector-like pairs persist in the Higgs sector without an obvious symmetry to protect them may shed light on new solutions to the mu problem in F-theory GUTs.Comment: 95 pages (71 pages + 1 Appendix); v2 references added, minor correction

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

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

Astrocytes convert network excitation to tonic inhibition of neurons

<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na⁺concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg²⁺] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p

Interaction between Purkinje Cells and Inhibitory Interneurons May Create Adjustable Output Waveforms to Generate Timed Cerebellar Output

We develop a new model that explains how the cerebellum may generate the timing in classical delay eyeblink conditioning. Recent studies show that both Purkinje cells (PCs) and inhibitory interneurons (INs) have parallel signal processing streams with two time scales: an AMPA receptor-mediated fast process and a metabotropic glutamate receptor (mGluR)-mediated slow process. Moreover, one consistent finding is an increased excitability of PC dendrites (in Larsell's lobule HVI) in animals when they acquire the classical delay eyeblink conditioning naturally, in contrast to in vitro studies, where learning involves long-term depression (LTD). Our model proposes that the delayed response comes from the slow dynamics of mGluR-mediated IP3 activation, and the ensuing calcium concentration change, and not from LTP/LTD. The conditioned stimulus (tone), arriving on the parallel fibers, triggers this slow activation in INs and PC spines. These excitatory (from PC spines) and inhibitory (from INs) signals then interact at the PC dendrites to generate variable waveforms of PC activation. When the unconditioned stimulus (puff), arriving on the climbing fibers, is coupled frequently with this slow activation the waveform is amplified (due to an increased excitability) and leads to a timed pause in the PC population. The disinhibition of deep cerebellar nuclei by this timed pause causes the delayed conditioned response. This suggested PC-IN interaction emphasizes a richer role of the INs in learning and also conforms to the recent evidence that mGluR in the cerebellar cortex may participate in slow motor execution. We show that the suggested mechanism can endow the cerebellar cortex with the versatility to learn almost any temporal pattern, in addition to those that arise in classical conditioning

The Specification and Global Reprogramming of Histone Epigenetic Marks during Gamete Formation and Early Embryo Development in C. elegans

In addition to the DNA contributed by sperm and oocytes, embryos receive parent-specific epigenetic information that can include histone variants, histone post-translational modifications (PTMs), and DNA methylation. However, a global view of how such marks are erased or retained during gamete formation and reprogrammed after fertilization is lacking. To focus on features conveyed by histones, we conducted a large-scale proteomic identification of histone variants and PTMs in sperm and mixed-stage embryo chromatin from C. elegans, a species that lacks conserved DNA methylation pathways. The fate of these histone marks was then tracked using immunostaining. Proteomic analysis found that sperm harbor ?2.4 fold lower levels of histone PTMs than embryos and revealed differences in classes of PTMs between sperm and embryos. Sperm chromatin repackaging involves the incorporation of the sperm-specific histone H2A variant HTAS-1, a widespread erasure of histone acetylation, and the retention of histone methylation at sites that mark the transcriptional history of chromatin domains during spermatogenesis. After fertilization, we show HTAS-1 and 6 histone PTM marks distinguish sperm and oocyte chromatin in the new embryo and characterize distinct paternal and maternal histone remodeling events during the oocyte-to-embryo transition. These include the exchange of histone H2A that is marked by ubiquitination, retention of HTAS-1, removal of the H2A variant HTZ-1, and differential reprogramming of histone PTMs. This work identifies novel and conserved features of paternal chromatin that are specified during spermatogenesis and processed in the embryo. Furthermore, our results show that different species, even those with diverged DNA packaging and imprinting strategies, use conserved histone modification and removal mechanisms to reprogram epigenetic information

Lithium-Ion Capacitors: Characterization and Modeling at Both High and Low Temperatures

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