76 research outputs found
Problems of the English Abbreviations in Medical Translation
AbstractThe article deals with the attempt to verify the prevalence of abbreviation-related problems in medical translation over other problematic lexical groups. Medical abbreviations appear extremely fast in modern English, evidenced by abbreviations that are not registered in dictionaries. As a result, the main problem of medical abbreviations translation is that the same abbreviations may have different meanings, depending on the disease, anatomy, or procedure being discussed. The aim of the paper is to study general and nationally specific features of the English medical abbreviations, to survey extra- and intralinguistic requisites of their formation, to determine regularities of medical abbreviations usage in modern English, to analyze peculiarity of classification of abbreviations. Special attention was also given to investigating some basic procedures applicable in translating them. We used such research methods as the method of component analysis of meaning based on dictionary definitions, the method of contextual analysis of the abbreviations, identifying their situational relevance. We also collected and processed nonregistered English medical abbreviations. Continuous sampling of the studied units of scientific and medical texts identified corpus examples. Material for the study was selected from articles, periodical literature on medicine and its related branches of science, from encyclopedic dictionaries. In conclusion, ordering of abbreviation in medicine can be achieved through a more thorough study of medical abbreviations, their proper use in medical professionals training and by means of modeling, which fixes the most convenient, concise and succinct clichés in medical discourse
In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants
Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally
Molecular Inferences Suggest Multiple Host Shifts of Rabies Viruses from Bats to Mesocarnivores in Arizona during 2001–2009
In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001–2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T242 in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other approaches
Ebolavirus species-specific interferon antagonism mediated by VP24
Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic, and Reston (RESTV) is not known to cause a disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously, we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with a reduced inhibition in IFN-I signaling. We hypothesized that modification of eVP24-karyopherin alpha interface to make it similar to bVP24 would attenuate the ability to antagonize IFN-I response. We generated a panel of recombinant EBOVs containing single or combinations of point mutations in the eVP24-karyopherin alpha interface. Most of the viruses appeared to be attenuated in both IFN-I-competent 769-P and IFN-I-deficient Vero-E6 cells in the presence of IFNs. However, the R140A mutant grew at reduced levels even in the absence of IFNs in both cell lines, as well as in U3A STAT1 knockout cells. Both the R140A mutation and its combination with the N135A mutation greatly reduced the amounts of viral genomic RNA and mRNA suggesting that these mutations attenuate the virus in an IFN-I-independent attenuation. Additionally, we found that unlike eVP24, bVP24 does not inhibit interferon lambda 1 (IFN-λ1), interferon beta (IFN-β), and ISG15, which potentially explains the lower pathogenicity of BDBV relative to EBOV. Thus, the VP24 residues binding karyopherin alpha attenuates the virus by IFN-I-dependent and independent mechanisms
Deciphering Three Beneficial Effects of 2,2 '-Bipyridine-N,N '-Dioxide on the Luminescence Sensitization of Lanthanide(III) Hexafluoroacetylacetonate Ternary Complexes
Lanthanide hexafluoroacetylacetonate ternary complexes with 2,2'-bipyridine-N,N'-dioxide, [Ln(hfa)3(bpyO2)], were synthesized for Ln = Eu, Gd, Tb, and Lu and fully characterized by elemental, thermal, and mass-spectrometric analyses. The X-ray crystal structure of [Eu(hfa) 3(bpyO2)].0.5C6H6 reveals an octa-coordinate metal ion lying in a severely distorted trigonal dodecahedron geometry; the Eu-O distances lie in the range 2.36-2.44 Å with no significant difference between hfa- and bpyO2. A detailed comparative photophysical investigation has been carried out to determine the exact influence of the introduction of bpyO2 in the inner coordination sphere of the metal ion in replacement of the two water molecules in [Ln(hfa)3(H2O)2]. While this replacement is detrimental for Tb, it leads to a 15-fold increase in the overall quantum yield for Eu. This large improvement originates from (i) a better sensitization efficiency, the ancillary ligand being responsible for 3/4 of the energy transfer, (ii) elimination of nonradiative deactivation pathways through harmonics of O-H vibrations, and (iii) reduction in the radiative lifetime. The latter influence is rarely documented, but it accounts here for ã25% increase in the intrinsic quantum yield, so that more attention should be given to this parameter when designing highly luminescent lanthanide complexes. © 2011 American Chemical Society
Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies
Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies
Hydrothermal Transformations of Lanthanum Phosphate with iron(3+) Oxides (Hydroxides) in Acidic Solutions
Получены данные по влиянию природы минеральных кислот на показатели
вскрытия фосфата лантана новым методом – гидротермальным кислотным растворением
фосфата лантана при температуре 180–220 °C в присутствии оксидов (гидроксидов) железа(3+).
Установлено, что из изученных кислот – азотной, хлористоводородной и серной – эффективное
извлечение лантана с глубоким обесфосфориванием растворов достигается лишь для азотной
кислоты. В этой системе извлечение лантана в раствор составляет 97–98 %, а содержание фосфора
снижается до 10 мг/л и менее за счет образования устойчивого гидроксифосфата железа(3+) –
гиниита. Для соляной кислоты наблюдается преимущественный переход в раствор железа(3+)
за счет комплексообразования его с хлорид-ионами,
а показатели извлечения в раствор лантана
не превышали 5 %. Содержание фосфора в растворе также существенно выше, чем для азотной
кислоты. При использовании серной кислоты образуются малорастворимые гидроксисульфаты.
Фазы образования гиниита не наблюдаются, а извлечение в раствор лантана не превышает 10 %
для концентрации серной кислоты 4 моль/лData on the influence of the nature of mineral acids on the indicators of lanthanum phosphate opening by a new method – hydrothermal acid dissolution of lanthanum phosphate at a temperature of 180–220 °C in the presence of iron(3+) oxides (hydroxides) have been obtained. It has been established that from the studied acids – nitric, hydrochloric and sulfuric, effective extraction of lanthanides with deep dephosphorization of solutions is achieved only for nitric acid. In this system, the extraction of lanthanum into solution is 97–98 %, and the phosphorus content is reduced to 10 mg/L or less due to the formation of stable iron(3+) hydroxyphosphate – giniite. For hydrochloric acid, a preferential transition to iron(3+) solution is observed due to its complexation with chloride ions, and the extraction rates of lanthanum into the solution did not exceed 5 %. The content of phosphorus in the solution is also significantly higher than for nitric acid. When using sulfuric acid, sparingly soluble hydroxysulfates are formed. The phase of gyniite formation is not observed, and the extraction of lanthanum into solution does not exceed 10 % for a sulfuric acid concentration of 4 mol/
Population dynamics and demographic history of Eurasian collared lemmings.
BACKGROUND: Ancient DNA studies suggest that Late Pleistocene climatic changes had a significant effect on population dynamics in Arctic species. The Eurasian collared lemming (Dicrostonyx torquatus) is a keystone species in the Arctic ecosystem. Earlier studies have indicated that past climatic fluctuations were important drivers of past population dynamics in this species. RESULTS: Here, we analysed 59 ancient and 54 modern mitogenomes from across Eurasia, along with one modern nuclear genome. Our results suggest population growth and genetic diversification during the early Late Pleistocene, implying that collared lemmings may have experienced a genetic bottleneck during the warm Eemian interglacial. Furthermore, we find multiple temporally structured mitogenome clades during the Late Pleistocene, consistent with earlier results suggesting a dynamic late glacial population history. Finally, we identify a population in northeastern Siberia that maintained genetic diversity and a constant population size at the end of the Pleistocene, suggesting suitable conditions for collared lemmings in this region during the increasing temperatures associated with the onset of the Holocene. CONCLUSIONS: This study highlights an influence of past warming, in particular the Eemian interglacial, on the evolutionary history of the collared lemming, along with spatiotemporal population structuring throughout the Late Pleistocene
IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern
Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern
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