Very-wide-field camera. Proposal of Space Astronomy Laboratory for second Spacelab mission

A proposal is made for inclusion of a very wide field camera onboard Spacelab. Its scientific program is outlined: detection and photometry, spectrography, and star and starlike object photography. The optics, receptor, and mechanical structure are described. Scientific and technical constraints are discussed, and a development plan is detailed. The dust contamination of Spacelab using the camera was also studied

Translatomics Study of Chinese Hamster Ovary Cell Cultures

Ph.DDOCTOR OF PHILOSOPH

Ejection of Matter and Energy from NGC 4258

It has been claimed that the megamaser observations of the nucleus of NGC 4258 show that a massive black hole is present in its center (Miyoshi et al. 1995, Greenhill et al. 1995). We show that the evidence of ejection of gas, radio plasma, and X-ray emitting QSOs from this nucleus all show that the ejection is coming from the center in a curving flow within a cone with angle ~40 degrees, centered at P.A. 100 degrees. This is close to the direction in which the velocities from the megamaser have been measured, so that the evidence taken as a whole suggests that the masering gas also is being ejected in the same direction at velocities +/- 900 km/sec and not rotating about a massive black hole. Thus it does not provide evidence for a black hole in the center. Subject headings: galaxies: nuclei: individual (NGC 4258) -- black holes -- masersComment: 7 pages, 1 Figure, LaTex using epsf.tex, submitted to Ap.J.Letter

Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression

Treatment-resistant depression (TRD) is a term used to describe a particular type of major depressive disorder (MDD). There is no consensus about what defines TRD, with various studies describing between 1 and 4 failures of antidepressant therapies, with or without electroconvulsive therapy (ECT). That is why TRD is such a growing concern among clinicians and researchers, and it explains the necessity for investigating novel therapeutic targets beyond conventional monoamine pathways. An imbalance between two primary central nervous system (CNS) neurotransmitters, L-glutamate and γ-aminobutyric acid (GABA), has emerged as having a key role in the pathophysiology of TRD. In this review, we provide an evaluation and comprehensive review of investigational antidepressants targeting these two systems, accessing their levels of available evidence, mechanisms of action, and safety profiles. N-methyl-D-aspartate (NMDA) receptor antagonism has shown the most promise amongst the glutamatergic targets, with ketamine and esketamine (Spravato) robustly generating responses across trials. Two specific NMDA-glycine site modulators, D-cycloserine (DCS) and apimostinel, have also generated promising initial safety and efficacy profiles, warranting further investigation. Combination dextromethorphan-bupropion (AXS-05/Auvelity) displays a unique mechanism of action and demonstrated positive results in particular applicability in subpopulations with cognitive dysfunction. Currently, the most promising GABA modulators appear to be synthetic neurosteroid analogs with positive GABAA receptor modulation (such as brexanolone). Overall, advances in the last decade provide exciting perspectives for those who do not improve with conventional therapies. Of the compounds reviewed here, three are approved by the Food and Drug Administration (FDA): esketamine (Spravato) for TRD, Auvelity (dextromethorphan-bupropion) for major depressive disorder (MDD), and brexanolone (Zulresso) for post-partum depression (PPD). Notably, some concerns have arisen with esketamine and brexanolone, which will be detailed in this study

Non-Canonical Pathways in the Pathophysiology and Therapeutics of Bipolar Disorder

Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and drug development. However, as a polygenic disorder, the neurobiology of BD is complex and involves biological changes in several organelles and downstream targets (pre-, post-, and extra-synaptic), including mitochondrial dysfunction, oxidative stress, altered monoaminergic and glutamatergic systems, lower neurotrophic factor levels, and changes in immune-inflammatory systems. The field has thus moved toward identifying more precise neurobiological targets that, in turn, may help develop personalized approaches and more reliable biomarkers for treatment prediction. Diverse pharmacological and non-pharmacological approaches targeting neurobiological pathways other than neurotransmission have also been tested in mood disorders. This article reviews different neurobiological targets and pathophysiological findings in non-canonical pathways in BD that may offer opportunities to support drug development and identify new, clinically relevant biological mechanisms. These include: neuroinflammation; mitochondrial function; calcium channels; oxidative stress; the glycogen synthase kinase-3 (GSK3) pathway; protein kinase C (PKC); brain-derived neurotrophic factor (BDNF); histone deacetylase (HDAC); and the purinergic signaling pathway

Chandra Observations and the Nature of the Anomalous Arms of NGC 4258 (M 106)

This paper presents high resolution X-ray observations with Chandra of NGC 4258 and infers the nature of the so called ``anomalous arms'' in this galaxy. The anomalous arms dominate the X-ray image; diffuse X-ray emission from the ``plateaux'' regions, seen in radio and H$\alpha$ imaging, is also found. X-ray spectra have been obtained at various locations along the anomalous arms and are well described by thermal (mekal) models with kT in the range 0.37 - 0.6 keV. The previously known kpc-scale radio jets are surrounded by cocoons of hot X-ray emitting gas for the first 350 pc of their length. The radio jets, seen in previous VLBA and VLA observations, propagate perpendicular to the compact nuclear gas disk (imaged in water vapor maser emission). The angle between the jets and the rotation axis of the galactic disk is 60$^{\circ}$. The jets shock the normal interstellar gas along the first 350 pc of their length, causing the hot, X-ray emitting cocoons noted above. At a height of z = 175 pc from the disk plane, the jets exit the normal gas disk and then propagate though the low density halo until they reach ``hot spots'' (at 870 pc and 1.7 kpc from the nucleus), which are seen in radio, optical line and X-ray emission. These jets must drive mass motions into the low density halo gas. This high velocity halo gas impacts on the dense galactic gas disk and shock heats it along and around a ``line of damage'', which is the projection of the jets onto the galactic gas disk as viewed down the galaxy disk rotation axis. However, because NGC 4258 is highly inclined ($i$ = 64$^{\circ}$), the ``line of damage'' projects on the sky in a different direction to the jets themselves. We calculate the expected p.a. of the ``line of damage'' on the sky and find that it coincides with the anomalous arms to within 2$^{\circ}$. (Abstract truncated).Comment: 12 pages plus 9 figures, to be published in the Astrophysical Journal, v560, nr 1, pt 1 (Oct 10, 2001 issue