ABSTRACT
The quantum regime of a plasma-whistler-wave-pumped free-electron laser (FEL) in the presence of an axial-guide magnetic field is presented. By quantizing both the plasma whistler field and axial magnetic field, an N-particle three-dimensional Hamiltonian of quantum-FEL (QFEL) has been derived. Employing Heisenberg evolution equations and introducing a new collective operator which controls the vertical motion of electrons, a quantum dispersion relation of the plasma whistler wiggler has been obtained analytically. Numerical results indicate that, by increasing the intrinsic quantum momentum spread and/or increasing the axial magnetic field strength, the bunching and the radiation fields grow exponentially. In addition, a spiking behavior of the spectrum was observed with increasing cyclotron frequency which provides an enormous improvement in the coherence of QFEL radiation even in a limit close-to-classical regime, where an overlapping of these spikes is observed. Also, an upper limit of the intrinsic quantum momentum spread which depends on the value of the cyclotron frequency was found.
ABSTRACT
Endoplasmic reticulum (ER) release and cell-surface export of many G protein-coupled receptors (GPCRs) are tightly regulated. For gamma-aminobutyric acid (GABA)B receptors of GABA, the major mammalian inhibitory neurotransmitter, the ligand-binding GB1 subunit is maintained in the ER by unknown mechanisms in the absence of hetero-dimerization with the GB2 subunit. We report that GB1 retention is regulated by a specific gatekeeper, PRAF2. This ER resident transmembrane protein binds to GB1, preventing its progression in the biosynthetic pathway. GB1 release occurs upon competitive displacement from PRAF2 by GB2. PRAF2 concentration, relative to that of GB1 and GB2, tightly controls cell-surface receptor density and controls GABAB function in neurons. Experimental perturbation of PRAF2 levels in vivo caused marked hyperactivity disorders in mice. These data reveal an unanticipated major impact of specific ER gatekeepers on GPCR function and identify PRAF2 as a new molecular target with therapeutic potential for psychiatric and neurological diseases involving GABAB function.
Subject(s)
Carrier Proteins/metabolism , Endoplasmic Reticulum/metabolism , Membrane Proteins/metabolism , Receptors, GABA-B/metabolism , Amino Acid Sequence , Animals , Cell Line , Cell Membrane/metabolism , HEK293 Cells , Humans , Mice , Mice, Knockout , Protein Multimerization , Protein Subunits , gamma-Aminobutyric Acid/metabolismABSTRACT
BACKGROUND: Brain metastases (BM) from the gastrointestinal tract (GIT) cancers are relatively rare. Despite those advances in diagnostic and treatment options, life expectancy and quality of life in these patients are still poor. In this review, we present an overview of the studies which have been previously performed as well as a comprehensive strategy for the assessment and treatment of BM from the GIT cancers. METHOD: To obtain information on brain metastases from GIT, we performed a systematic review of Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The collected data included patient characteristics, primary tumor data and brain metastases data. RESULT: In our search of the literature, we found 74 studies between 1980 and 2011, which included 2538 patients with brain metastases originated from gastrointestinal cancer. Analysis of available data showed that among 2538 patients who had brain metastases from GIT, a total of 116 patients (4.57%) had esophageal cancer, 148 patients (5.83%) had gastric cancer, 233 patients (9.18%) had liver cancer, 13 patients had pancreas cancer (0.52%) and 2028 patients (79.90%) had colorectal cancer. The total median age of the patients was 58.9 years. CONCLUSION: Brain metastases have been considered the most common structural neurological complication of systemic cancer. Due to poor prognosis they influence the survival rate as well as the quality of life of the patients. The treatment of cerebral metastasis depends on the patients' situation and the decisions of the treating physicians. The early awareness of a probable metastasis from GI to the brain will have a great influence on treatment outcomes as well as the survival rate and the quality-of-life of the patients.
