442 research outputs found
Florida Gun Laws Weaken: Another Setback for the Mass Shooting Generation
While gun control has been a topic of controversy in the United States for decades, one area that has seemed undebatable is the protection of children from gun violence in our Nation’s schools. The methods of achieving this end goal vary from state to state. Some states have continued the longstanding tradition of designating schools as “gun-free zones,” while others have employed armed security guards. Florida has chosen the latter option for its public and charter schools. However, the Florida Legislature has taken a dramatic deviation from this path that will negatively affect students attending private religious schools: it passed a law that allows religious institutions that are attached to a school to decide to allow concealed carry permit holders to bring weapons on their grounds.
The passage of this law sparked traditional gun debate arguments. Gun rights activists voiced their opinions by saying that although this was a small step, it was a step in the right direction. Opponents of the law, including parents, preachers, and organizations, are unsettled by the new law and fear that the safety of the children attending these schools has been compromised. This article discusses the meaning of the new law and illustrates its shortcomings. It explains the implications of this law and argues why it should be repealed
Investigating the Interactions Between Individual Calmodulin and HIV-1 Protein Domains
The World Health Organization found that 37.9 million people were living with HIV by the end of 2018. HIV is a virus that weakens the immune system through viral replication and the destruction of CD4+ T-cells, which are white blood cells that detect infection and make antibodies. A cure for HIV has not yet been discovered. HIV-1 contains a Gag polyprotein which regulates the stages of viral replication. Previous studies suggest that the myristoyl group of a matrix protein peptide found on the Gag polyprotein, MA, forms a complex with a calcium-binding, multifunctional regulatory protein called Calmodulin (CaM). CaM has also been found to be upregulated upon HIV infection. The MA/CaM complex induces extended conformation and causes a decrease in the compact structure of MA, which is predicted to impact the accessibility of interaction sites within MA and lead to rapid HIV viral production. Through hindering the myristoyl group on MA, it is possible that production of HIV can be greatly decreased. Before exploring this possibility, it is first necessary that the site and mechanism of the protein-protein interaction is identified and understood. For this reason, our lab is investigating the interactions of the independent N-terminal and C-terminal domains of MA and CaM. The MA protein has tryptophan-containing helices on its domains which allows for quantification using fluorescence spectroscopy and anisotropy. By investigating each protein domain and tryptophan signal separately, the location where binding occurs can be isolated and it can be determined if the interaction of one CaM or MA domain is required, or a prerequisite, for the interaction of the other. Identifying how each protein domain is involved enhances current understanding of HIV production and is a significant step in determining a possible solution for inhibiting HIV-1 replication
Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (M\u3csup\u3epro\u3c/sup\u3e)
The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with the current computation advancements. Here, a dataset of 406,747 unique NPs was screened against the SARS-CoV-2 main protease (Mpro) crystal structure (6lu7) using a combination of ligand- and structural-based virtual screening. Based on 1) the predicted binding affinities of the NPs to the Mpro, 2) the types and number of interactions with the Mpro amino acids that are critical for its function, and 3) the desirable pharmacokinetic properties of the NPs, we identified the top 20 candidates that could potentially inhibit the Mpro protease function. A total of 7 of the 20 top candidates were subjected to in vitro protease inhibition assay and 4 of them (4/7; 57%), including two beta carbolines, one N-alkyl indole, and one Benzoic acid ester, had significant inhibitory activity against Mpro protease. These four NPs could be developed further for the treatment of COVID-19 symptoms
Antimicrobial Susceptibilities of Aerobic Isolates from Respiratory Samples of Young New Zealand Horses
3rd Annual IEEE Energy Conversion Congress and Exposition, ECCE 2011, Phoenix, AZ, 17-22 September 2011This paper presents a method of mitigating the transient overshoots of DC-DC converters operating with large load disturbances. The method involves a small auxiliary power circuit with a complementary control scheme that provides a smooth absorption and release of excess energy from and to the main DC-DC converter in the events of large load changes. This control mechanism interactively mitigates the large transient overshoots which would otherwise appear at the converter output. Since the control scheme involves an adjustable-energy-storage feature, the proposed solution is effective for any level of step-load change within a pre-specified range.Department of Electronic and Information EngineeringRefereed conference pape
A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase
Inositol pentakisphosphate 2-kinase catalyzes the phosphorylation of the axial 2-OH of myo-inositol 1,3,4,5,6-pentakisphosphate for de novo synthesis of myo-inositol hexakisphosphate. Disruption of inositol pentakisphosphate 2-kinase profoundly influences cellular processes; from nuclear mRNA export and phosphate homeostasis in yeast and plants, to establishment of left-right asymmetry in zebra fish. We elaborate an active site fluorescent probe that allows high throughput screening of Arabidopsis inositol pentakisphosphate 2-kinase. We show that the probe has a binding constant comparable to the Km values of inositol phosphate substrates of this enzyme, and can be used to prospect for novel substrates and inhibitors of inositol phosphate kinases. We identify several micromolar Ki inhibitors and validate this approach by solving the crystal structure of protein in complex with purpurogallin. We additionally solve structures of protein in complexes with epimeric higher inositol phosphates. This probe may find utility in characterization of a wide family of inositol phosphate kinases
Water sources and mixing in riparian wetlands revealed by tracers and geospatial analysis
Acknowledgments We thank the European Research Council (ERC) (project GA 335910 VEWA) and Natural Environment Research Council (NERC) (project NE/K000268/1) for funding and the Airborne Research and Survey Facility for conducting the aerial survey. The data used are available from the authors. In addition, we would like to thank the additional support from Audrey Innes for the sample analysis and Maria Blumstock and Mike Kennedy for assisting with field work.Peer reviewedPublisher PD
Change: A Leader’s Perspective
Change: A Leader\u27s Perspective represents the culmination of the Change Leadership course taught at Winona State University in the fall term of 2017. Leadership is a broad category with many facets. This book explores the subject and offers students of leadership and aspiring leaders current perspectives on leadership theories, the omnipresence of change, and personal reflections on the course material. Additional thoughts which resonate throughout this text are that leaders influence outcomes and that leadership manifests itself in change, whether by cause or effect.https://openriver.winona.edu/leadershipeducationbooks/1000/thumbnail.jp
The 1.6 micron near infrared nuclei of 3C radio galaxies: Jets, thermal emission or scattered light?
Using HST NICMOS 2 observations we have measured 1.6-micron near infrared
nuclear luminosities of 100 3CR radio galaxies with z<0.3, by modeling and
subtracting the extended emission from the host galaxy. We performed a
multi-wavelength statistical analysis (including optical and radio data) of the
properties of the nuclei following classification of the objects into FRI and
FRII, and LIG (low-ionization galaxies), HIG (high-ionization galaxies) and BLO
(broad-lined objects) using the radio morphology and optical spectra,
respectively. The correlations among near infrared, optical, and radio nuclear
luminosity support the idea that the near infrared nuclear emission of FRIs has
a non-thermal origin. Despite the difference in radio morphology, the
multi-wavelength properties of FRII LIG nuclei are statistically
indistinguishable from those of FRIs, an indication of a common structure of
the central engine. All BLOs show an unresolved near infrared nucleus and a
large near infrared excess with respect to FRII LIGs and FRIs of equal radio
core luminosity. This requires the presence of an additional (and dominant)
component other than the non-thermal light. Considering the shape of their
spectral energy distribution, we ascribe the origin of their near infrared
light to hot circumnuclear dust. A near infrared excess is also found in HIGs,
but their nuclei are substantially fainter than those of BLO. This result
indicates that substantial obscuration along the line-of-sight to the nuclei is
still present at 1.6 micron. Nonetheless, HIGs nuclei cannot simply be
explained in terms of dust obscuration: a significant contribution from light
reflected in a circumnuclear scattering region is needed to account for their
multiwavelength properties.Comment: 20 pages, 16 figures. Accepted for publication on Ap
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Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM
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