ABSTRACT
We describe a case of traumatic lingual hematoma in a patient on dual antiplatelet therapy. After securing the airway, bilateral lingual artery embolization successfully halted expanding hematoma formation. Patient subsequently required tracheostomy for continued airway edema. Although patient course was wrought with postoperative complications, we review this case to illustrate how prompt hematoma evacuation and embolization can resolve significant vasovagal bradycardia and hypotension secondary to expansile lingual hematoma.
ABSTRACT
Energy differences between analogue states in the T=1/2 ^{23}Mg-^{23}Na mirror nuclei have been measured along the rotational yrast bands. This allows us to search for effects arising from isospin-symmetry-breaking interactions (ISB) and/or shape changes. Data are interpreted in the shell model framework following the method successfully applied to nuclei in the f_{7/2} shell. It is shown that the introduction of a schematic ISB interaction of the same type of that used in the f_{7/2} shell is needed to reproduce the data. An alternative novel description, applied here for the first time, relies on the use of an effective interaction deduced from a realistic charge-dependent chiral nucleon-nucleon potential. This analysis provides two important results: (i) The mirror energy differences give direct insight into the nuclear skin; (ii) the skin changes along the rotational bands are strongly correlated with the difference between the neutron and proton occupations of the s_{1/2} "halo" orbit.
ABSTRACT
On-chip energy storage and management will have transformative impacts in developing advanced electronic platforms with built-in energy needs for operation of integrated circuits driving a microprocessor. Though success in growing stand-alone energy storage elements such as electrochemical capacitors (super and pseusocapacitors) on a variety of substrates is a promising step towards this direction. In this work, on-chip energy storage is demonstrated using architectures of highly aligned vertical carbon nanotubes (CNTs) acting as supercapacitors, capable of providing large device capacitances. The efficiency of these structures is further increased by incorporating electrochemically active nanoparticles such as MnOx to form pseudocapacitive architectures thus enhancing device capacitance areal specific capacitance of 37 mF/cm2. The demonstrated on-chip integration is up and down-scalable, compatible with standard CMOS processes, and offers lightweight energy storage what is vital for portable and autonomous device operation with numerous advantages as compared to electronics built from discrete components.
ABSTRACT
Two pairs of positive-and negative-parity doublet bands together with eight strong electric dipole transitions linking their yrast positive- and negative-parity bands have been identified in ^{78}Br. They are interpreted as multiple chiral doublet bands with octupole correlations, which is supported by the microscopic multidimensionally-constrained covariant density functional theory and triaxial particle rotor model calculations. This observation reports the first example of chiral geometry in octupole soft nuclei.
ABSTRACT
Following the earlier detection of six new esterified fumonisin B1 (EFB1) isomers containing three acyl groups in a Fusarium verticillioides-inoculated rice culture, it was assumed that linoleic, palmitic or oleic acid esterifies one of the free OH groups on the fumonisin backbone. On the basis of the results of our recent investigations we now propose that these EFB1 isomers are actually 3-O- and 5-O-acyl derivatives of FB1 (3-O-linoleoyl-FB1, 5-O-linoleoyl-FB1, 3-O-palmitoyl-FB1, 5-O-palmitoyl-FB1, 3-O-oleoyl-FB1 and 5-O-oleoyl-FB1). A F. verticillioides strain was identified that produced not only O-acyl-FB1 isomers, but also low amounts of three N-acyl derivatives (N-linoleoyl-FB1, N-palmitoyl-FB1 and N-oleoyl-FB1), which eluted from the HPLC column after the six O-acyl compounds and in the same sequence as for the O-acyl compounds. The characteristic positive and negative ESI-MS/MS spectra obtained after solid-phase extraction of the culture extract facilitated identification of these N-acyl-FB1 derivatives. The biosynthesis of N-palmitoyl-FB1 by F. verticillioides was verified by spiking the culture extract with synthetic N-palmitoyl-FB1. This is the first report of the separation and mass spectrometric identification of the six O-acyl- and three N-acyl-FB1 derivatives extracted from a F. verticillioides culture.
Subject(s)
Ceramides/analysis , Fumonisins/analysis , Fusarium/metabolism , Linoleic Acid/analysis , Oleic Acid/analysis , Palmitic Acid/analysis , Carcinogens, Environmental/analysis , Carcinogens, Environmental/chemistry , Carcinogens, Environmental/metabolism , Ceramides/chemistry , Ceramides/metabolism , Chromatography, High Pressure Liquid , Esterification , Fatty Acids/analysis , Fatty Acids/chemistry , Fatty Acids/metabolism , Food Contamination , Food Inspection/methods , Fumonisins/chemistry , Fumonisins/metabolism , Hungary , Isomerism , Linoleic Acid/chemistry , Linoleic Acid/metabolism , Molecular Structure , Oleic Acid/chemistry , Oleic Acid/metabolism , Oryza/chemistry , Oryza/microbiology , Palmitic Acid/chemistry , Palmitic Acid/metabolism , Seeds/chemistry , Seeds/microbiology , Solid Phase Extraction , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.
ABSTRACT
RSV is a major cause of pediatric respiratory tract disease worldwide, but a vaccine is not yet available. It is now possible to prepare live infectious RSV completely from cDNA. This provides a method for introducing defined mutations into infectious virus, making possible the rational design of a live-attenuated vaccine virus for intranasal administration. This is particularly important for RSV, for which achieving the appropriate balance between attenuation and immunogenicity by conventional methods has proven elusive. We took advantage of the existence of a panel of biologically derived vaccine candidate viruses that were incompletely attenuated but well characterized biologically. The mutations in these viruses were identified by sequence analysis and characterized by insertion into recombinant virus, thereby providing a menu of known attenuating mutations. These included a series of amino acid point mutations, mostly in the L polymerase, and a nucleotide substitution in a transcription gene-start signal, a cis-acting RNA element. The second source of mutations was from experimental mutational analysis of recombinant virus and involves deletion of the NS1, NS2, or SH gene. We have reconstructed a previously tested, biologically derived attenuated virus, cpts248/404, in recombinant form and are now proceeding to introduce additional mutations from the menu to achieve stepwise increases in attenuation. The ability to modify the attenuation phenotype incrementally in a directed manner should result in an appropriate vaccine virus.
Subject(s)
Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Viruses/immunology , Vaccines, Attenuated , Vaccines, Synthetic , Viral Vaccines , DNA, Complementary/genetics , Drug Design , Humans , Respiratory Syncytial Viruses/geneticsABSTRACT
The live-attenuated respiratory syncytial virus vaccine candidate cpts530/1009 was previously shown to contain two separate amino acid changes in the L protein, mutations 530 and 1009 (Phe-521-->Leu and Met-1169-->Val, respectively, according to the amino acid sequence of the L protein). Each mutation independently specifies temperature-sensitive (ts) and attenuation phenotypes. In this study, we examined the effects of these mutations on transcription and RNA replication, using complete infectious recombinant virus as well as a plasmid-based minireplicon system, the latter under conditions in which effects on replication and transcription are uncoupled. In comparison with recombinant wild-type virus, the 530 and 1009 viruses were partially restricted at 37 degrees C for RNA replication, mRNA synthesis, and virus growth. The 1009 virus was partially restricted for RNA synthesis and virus growth even at 32 degrees C, which suggested that the 1009 mutation has a non-ts component in addition to the ts component. Interestingly, the synthesis of polycistronic readthrough mRNAs was elevated 1.6- to 3.8-fold for the 1009 virus, and this defect was non-ts. Studies with the minigenome system showed that the 530 and 1009 mutations each directly affect both replication and transcription, that the effect on replication was marginally greater than on transcription for the 530 mutation, and that the increase in readthrough mRNA associated with the 1009 mutation also was observed with the minigenome system.
Subject(s)
RNA, Messenger/biosynthesis , RNA, Viral/biosynthesis , Respiratory Syncytial Viruses/genetics , Transcription, Genetic , Viral Vaccines , Mutation , Temperature , Vaccines, AttenuatedABSTRACT
cpts530/1009 is a live-attenuated, temperature-sensitive (ts) RSV vaccine candidate that was shown previously to be attenuated for seronegative humans. It was generated by two rounds of chemical mutagenesis: first, a partially attenuated, cold-passaged (cp), non-ts RSV mutant (cpRSV) was mutagenized to yield the ts derivative cpts530, and then cpts530 was mutagenized to yield cpts530/1009, which is more ts. Previous nucleotide (nt) sequence analysis of cpts530 showed that it has a single nt change compared to cpRSV that results in an amino acid substitution at residue 521 in the L protein. Reverse genetics confirmed that this mutation is responsible for the ts phenotype of cpts530. Here, determination of the complete 15,222-nt sequence of cpts530/ 1009 identified a single change compared to cpts530, namely a point mutation at nt 12002, which results in a methionine-tovaline substitution at amino acid 1169 in the L protein. The contribution of the 1009 mutation to the level of temperature sensitivity and attenuation exhibited by cpts530/1009 was evaluated by its introduction alone or with the 530 and cp mutations into the full-length cDNA clone of wild-type (wt) RSV. Subsequent analysis of infectious viruses recovered from the mutant cDNAs indicated that (i) the 1009 mutation indeed was a ts mutation and the level of temperature sensitivity specified by the 1009 mutation was less than that specified by the 530 mutation, (ii) the 530 and 1009 mutations each contributed to attenuation in the upper respiratory tract of mice and their effects were additive, (iii) viruses bearing the 1009 mutation were more attenuated in the lower respiratory tract of mice than viruses bearing the 530 mutation and (iv) the combination of the 530 and 1009 mutations in the cpRSV background resulted in the same level of temperature sensitivity and attenuation in mice as that observed for the biologically-derived cpts530/1009 mutant. These data show that the genetic basis of the attenuation and temperature sensitivity of the cpts530/1009 candidate vaccine virus is the sum of the contributions of seven identified amino acid substitutions, i.e. the 5 cpRSV mutations, the 530 mutation and the 1009 mutation.
Subject(s)
HN Protein , Vaccines, Attenuated , Viral Proteins/immunology , Viral Vaccines , Amino Acid Substitution , Animals , Chlorocebus aethiops , Humans , Mice , Mice, Inbred BALB C , Mutagenesis, Site-Directed , Phenotype , RNA, Viral/chemistry , Respiratory Syncytial Viruses , Sequence Analysis , Structure-Activity Relationship , Temperature , Transfection , Vero Cells , Viral Envelope Proteins , Viral Proteins/chemistryABSTRACT
A set of five missense mutations previously identified by nucleotide sequence analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has been introduced into a recombinant wild-type strain of RSV. This recombinant virus, designated rA2cp, appears to replicate less efficiently in the upper and lower respiratory tracts of seronegative chimpanzees than either biologically derived or recombinant wild-type RSV. Infection with rA2cp also resulted in significantly less rhinorrhea and cough than infection with wild-type RSV. These findings confirm the role of the cp mutations in attenuation of RSV and identify their usefulness for inclusion in future live attenuated recombinant RSV vaccine candidates.
Subject(s)
Mutation , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/pathogenicity , Animals , Base Sequence , Cell Line , DNA, Viral , Humans , Molecular Sequence Data , Pan troglodytes , Recombination, GeneticABSTRACT
cpts530, a candidate live-virus vaccine, is an attenuated strain of human respiratory syncytial virus (RSV). It was derived by subjecting a cold-passaged (cp) strain of RSV to a single round of chemical mutagenesis. cpts530 is a temperature-sensitive (ts) mutant that is attenuated in mice and chimpanzees, and its ts phenotype exhibits a high level of stability during replication in both species. In the present study, the complete nucleotide sequence of cpts530 RSV was determined. The five mutations known to be present in the parent cpRSV were retained in its cpts530 derivative, and one additional nucleotide change was identified at nucleotide (nt) 10060, which resulted in a phenylalanine-to-leucine change at amino acid 521 in the large polymerase (L) protein. To determine if this single amino acid substitution was indeed responsible for the ts phenotype of cpts530, it was introduced alone or in combination with the cp mutations into the full-length cDNA clone of the wild-type A2 RSV. Analysis of infectious viruses recovered from mutant cDNAs indicated that this single mutation specified complete restriction of plaque formation of recombinant cp530 in HEp-2 cell monolayer cultures at 40 degrees C, and the level of temperature sensitivity was not influenced by the presence of the five cpRSV mutations. These findings identify the phenylalanine-to-leucine change at amino acid 521 in the L protein as the mutation that specifies the ts phenotype of cpts530. Furthermore, these findings illustrate the feasibility of using the cDNA-based recovery system to analyze and construct defined attenuated vaccine viruses.
Subject(s)
HN Protein , Respiratory Syncytial Virus, Human/immunology , Vaccines, Synthetic/genetics , Viral Proteins/genetics , Viral Vaccines/genetics , Mutation , Temperature , Vaccines, Attenuated/genetics , Viral Envelope ProteinsABSTRACT
The nucleocapsid protein (N) gene of two subgroup A and one subgroup B strains of avian pneumovirus has been cloned and sequenced. The gene of all three isolates comprised 1197 nucleotides (nt), which formed a single major open reading frame, potentially encoding a protein of 391 amino acid residues. The N gene of the two subgroup A isolates differed by only 1 nt but differed by 282 (24%) nt and 35 (11%) amino acids from the B isolate. The predicted protein was identical in length to that of human, bovine and ovine respiratory syncytial viruses, the amino acid identity being approximately 41% overall but with some regions of identity > 90%.
Subject(s)
Nucleocapsid/genetics , Pneumovirus/genetics , Sequence Analysis, DNA , Amino Acid Sequence , Animals , Base Sequence , Cell Line , Chlorocebus aethiops , Cloning, Molecular , DNA, Viral , Molecular Sequence Data , Pneumovirus/isolation & purification , Pneumovirus/metabolism , Turkeys/virology , Vero CellsABSTRACT
The putative attachment protein of the avian pneumovirus that causes turkey rhinotracheitis is, by analogy with mammalian pneumoviruses, expected to be the major antigenic determinant. We report the nucleotide sequence of the attachment (G) protein genes of five different continental European isolates and compare them with the previously published sequence of the G gene for the focal variant of a U.K. isolate. The nucleotide sequences and the predicted amino acid sequences indicate that there are at least two distinct subgroups, similar to the grouping described for human respiratory syncytial (RS) virus. The U.K. and French isolates form one group and the isolates from Spain, Italy and Hungary form a second. The two subgroups can be easily distinguished on the basis of restriction enzyme digestion of PCR-generated products representing the full-length gene. Within the subgroups the predicted G proteins were highly conserved (98.5 to 99.7% amino acid identity) compared to the levels of identity of RS virus G proteins in the same subgroup (80 to 95%). Between the avian pneumovirus subgroups described here there was an unexpected degree of divergence, the average amino acid identity between members of the two groups being only 38%. This compares with the 53% conservation seen between members of the RS virus subgroups A and B. Comparison of the predicted amino acid sequences showed that the G proteins of members of the two avian pneumovirus subgroups had similar structural features. All proteins had an amino-terminal membrane anchor and the positions of cysteine residues were highly conserved. The potential importance of the high level of variation between the two subgroups in terms of epidemiology of the disease is discussed.
Subject(s)
Genetic Variation , Glycoproteins/genetics , Pneumovirus/classification , Pneumovirus/genetics , Viral Envelope Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA Primers , Europe , Glycoproteins/chemistry , Humans , Molecular Sequence Data , Pneumovirus/isolation & purification , Polymerase Chain Reaction/methods , Respiratory Syncytial Viruses/classification , Respiratory Syncytial Viruses/genetics , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , South Africa , Turkeys , United Kingdom , Viral Envelope Proteins/chemistryABSTRACT
The lactate dehydrogenase isoenzyme patterns in 46 extraocular eye muscle samples removed at surgery for squint were determined by acrylamide-gel electrophoresis and reduction of NAD coupled with formazan reaction. Muscle type subunits predominated in the isoenzymes of the medial and lateral rectus muscles of emmetropic and hypermetropic eyes, whereas heart type subunits predominated in those of myopic eyes.