Spontaneous Hopf Fibration in the Two-Higgs-Doublet Model.

We show that energetic considerations enforce a Hopf fibration of the standard model topology within the 2HDM whose potential has either an SO(3) or U(1) Higgs-family symmetry. This can lead to monopole and vortex solutions. We find these solutions, characterize their basic properties and demonstrate the nature of the fibration along with the connection to Nambu's monopole solution. We point out that breaking of the U(1)_{EM} in the core of the defect can be a feature which leads to a nonzero photon mass there.

Stable Cosmic Vortons in Bosonic Field Theory.

Stable ring solutions supported by the angular momentum caused by superconducting charge and current have been suggested to exist in the gauged U(1)×U(1) field theory. We construct potentially cosmologically relevant solutions using gradient flow for the first time and present the strongest evidence to date that they are stable to axial and, crucially, nonaxial perturbations. More importantly, we illustrate quantitative agreement with semianalytic predictions based on the thin string approximation, which validates world sheet action approaches to their formation and evolution.

Repellent signaling by Slit requires the leucine-rich repeats.

Slit is a repellent axon guidance cue produced by the midline glia in Drosophila that is required to regulate the formation of contralateral projections and the lateral position of longitudinal tracts. Four sequence motifs comprise the structure of Slit: a leucine-rich repeat (LRR), epidermal growth factor-like (EGF) repeats, a laminin-like globular (G)-domain, and a cysteine domain. Here we demonstrate that the LRR is required for repellent signaling and in vitro binding to Robo. Repellent signaling by slit is reduced by point mutations that encode single amino acid changes in the LRR domain. By contrast to the EGF or G-domains, the LRR domain is required in transgenes to affect axon guidance. Finally, we show that the midline repellent receptor, Robo, binds Slit proteins with internal deletions that also retain repellent activity. However, Robo does not bind Slit protein missing the LRR. Taken together, our data demonstrate that Robo binding and repellent signaling by Slit require the LRR region.

Cortical spreading depression reversibly disrupts convulsive motor seizure expression in amygdala-kindled rats.

To determine the role of the frontal cortex in the generalization of limbic seizures, we first produced unilateral cortical spreading depression to reversibly suppress neuronal activity in the motor cortex and then triggered an amygdala-kindled seizure. Three minutes following induction of unilateral spreading depression, stimulation of the ipsilateral kindled amygdala produced only a brief electrographic seizure, and completely failed to produce the bilateral electrographic and clonic convulsive seizures that were normally present during control trials. A very different outcome occurred when unilateral spreading depression was induced in the cortex contralateral to the kindled amygdala. In these cases, the electrographic amygdala seizures were normal and bilateral like control trials, yet the clonic convulsive seizures were lateralized and appeared to be controlled by the non-depressed, kindled hemisphere. These lateralized convulsions were identical to those observed following forebrain commissurotomy, when direct communication between the frontal cortices was permanently severed. The results of the present study further define the pathways of temporal lobe seizure propagation, and highlight the important contribution frontal cortical regions provide to both the electrographic and convulsive expression of amygdala-kindled seizures by amplifying local seizures and projecting them into downstream brainstem and spinal cord circuits.

A retrospective evaluation of nifedipine therapy in Prinzmetal's angina.

A retrosepctive evaluation has been made of blood pressure, pulse rate, and number of anginal attacks per day in twenty-one patients diagnosed as Prinzmetal's Angina and treated with the investigational drug nifedipine. The effect of combining nifedipine with short- and long-acting nitrates or with propranolol was also evaluated. In consideration of the statisically significant reduction in the number of anginal attacks per day, p less than 0.001, together with the non-significant mean changes in blood pressure and pulse rate as well as the compatibility with the other drugs, it is concluded that nifedipine is a very useful drug, in a dose range of 30--120 mg per day, for the treatment of Prinzmetal's Angina. Recorded side-effects were of minimal severity and in no case caused nifedipine therapy to be discontinued.

Solitonic fullerene structures in light atomic nuclei.

The Skyrme model is a classical field theory which has topological soliton solutions. These solitons are candidates for describing nuclei, with an identification between the numbers of solitons and nucleons. We have computed numerically, using two different minimization algorithms, minimum energy configurations for up to 22 solitons. We find, remarkably, that the solutions for seven or more solitons have nucleon density isosurfaces in the form of polyhedra made of hexagons and pentagons. Precisely these structures arise, though at the much larger molecular scale, in the chemistry of carbon shells, where they are known as fullerenes.

Axon repulsion from the midline of the Drosophila CNS requires slit function.

Guidance of axons towards or away from the midline of the central nervous system during Drosophila embryogenesis reflects a balance of attractive and repulsive cues originating from the midline. Here we demonstrate that Slit, a protein secreted by the midline glial cells provides a repulsive cue for the growth cones of axons and muscle cells. Embryos lacking slit function show a medial collapse of lateral axon tracts and ectopic midline crossing of ventral muscles. Transgene expression of slit in the midline restores axon patterning. Ectopic expression of slit inhibits formation of axon tracts at locations of high Slit production and misdirects axon tracts towards the midline. slit interacts genetically with roundabout, which encodes a putative receptor for growth cone repulsion.

Survey of clinical experience with nimodipine in patients with subarachnoid hemorrhage.

The present studies show that nimodipine prevents and/or improves permanent ischemic neurological deficits in patients with subarachnoid hemorrhage. This was particularly marked in four double-blind, placebo-controlled studies in which statistically significant reductions in mortality and morbidity as consequence of cerebral vasospasm were found. The drug has been shown to increase cerebral blood flow, to reduce vasoconstriction, although not to fully prevent angiographic vasospasm, and to improve central conduction time. Nimodipine did not increase the rate of rebleeding. Its administration during anesthesia does not result in management problems. In general, nimodipine was well tolerated. Side effects were recorded mainly in open studies using the intravenous formulation and consisted mainly of decreases in blood pressure and headaches. Transient increases in liver enzymes may be due to the organic solvent. Hence, all results indicate that patients with subarachnoid hemorrhage will benefit from preventive or therapeutic nimodipine treatment.

Genetic analysis of vein function in the Drosophila embryonic nervous system.

The Drosophila epidermal growth factor receptor (EGFR) may be activated by two ligands expressed in the embryonic nervous system, Spitz and Vein. Previous studies have established Spitz as an essential activator of EGFR signaling in nervous system development. Here, we report the pattern of expression of vein mRNA in the nervous system and characterize the contribution of vein to cell lineage and axonogenesis. The number of midline glia (MG) precursors is reduced in vein mutants before the onset of embryonic apoptosis. In contrast to spitz, mis-expression of vein does not suppress apoptosis in the MG. These data indicate that early midline EGFR signaling, requiring vein and spitz, establishes MG precursor number, whereas later EGFR signals, requiring spitz, suppress apoptosis in the MG. vein mutants show early irregularities during axon tract establishment, which resolve later to variable defasciculation and thinner intersegmental axon tracts. vein and spitz phenotypes act additively in the regulation of MG cell number, but show synergism in a midline neuronal cell number phenotype and in axon tract architecture. vein appears to act downstream of spitz to briefly amplify local EGFR activation.

Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage.

We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.