557 research outputs found

    Mutation of a conserved, hydrophobic, cryptic epitope improves manufacturability and immunogenicity of the SARS-CoV-2 RBD

    Get PDF
    The supply of COVID-19 vaccine doses still lags behind the global demand for first time vaccination and booster doses. Distribution of vaccine doses has been far from equitable across the world given the steep prices and logistical challenges that low- and middle-income countries face. Subunit protein vaccine candidates have now been shown to elicit protective responses against SARS-CoV-2 infection, while providing additional benefits for manufacturing capability and stability requirements compared to many currently approved vaccines. Here we report a second-generation engineered RBD sequence variant with enhanced manufacturability and immunogenicity over the wild-type ancestral RBD and a first-generation engineered variant (RBD-L452K-F490W (RBD-J)). Introducing two additional mutations, S383D and L518D, to a hydrophobic cryptic epitope in the RBD core improved expression titers and biophysical stability compared to RBD-J. These two additional mutations in RBD-S383D-L452K-F490W-L518D (RBD-J6) ablated the interaction of two neutralizing antibodies, CR3022 and EY6A, targeting the class 4 epitope on the RBD core, but the protein is still bound by human convalescent sera. Mice immunized with a Beta sequence variant of RBD-J and RBD-J6 displayed on a virus-like particle were protected against challenges with Alpha and Beta variants of SARS-CoV-2. Sera from mice immunized with three doses of a RBD-J6 β – VLP showed comparable neutralizing activity to several variants of concern compared to two doses of Comirnaty. Please click Download on the upper right corner to see the full abstract

    Relaci\uf3n for\ue9tica de Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) y adultos de Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae)

    Get PDF
    BAUTISTA L, ARNAL E, APONTE O. 2005. Relaci\uf3n for\ue9tica de Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) y adultos de Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Entomotropica 20(1): 79-80. Phoresy of the mite Polyphagotarsonemus latus (Banks) on the white\ufb02y Bemisia tabaci (Gennadius) is reported for the \ufb01rst time in Venezuela. This relation was detected in plants of cucumber Cucumis sativus L. var. poinsett-76 (Cucurbitaceae) and sesame Sesamun indicum L. var. INIA-1 (Pedaliaceae) at "Experta Experimental Station", Agronomy School, Universidad Central de Venezuela, Maracay, Aragua state. This shows the important role that might play B. tabaci adults in the transportation and dispersion of a poliphagous pest as P. latus.BAUTISTA L, ARNAL E, APONTE O. 2005. Relaci\uf3n for\ue9tica de Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) y adultos de Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Entomotropica 20(1): 79-80. Se registra por primera vez en Venezuela la relaci\uf3n for\ue9tica del \ue1caro Polyphagotarsonemus latus (Banks) y la mosca blanca Bemisia tabaci (Gennadius). Dicha relaci\uf3n se detect\uf3 en plantas de pepino Cucumis sativus L. var. Poinsett-76 (Cucurbitaceae) y ajonjol\ued Sesamun indicum L. var. INIA-1 (Pedaliaceae), en la "Estaci\uf3n Experimental Experta", Facultad de Agronom\ueda, Universidad Central de Venezuela (UCV), Maracay, Estado Aragua. Este se\uf1alamiento, destaca la importancia que tienen los individuos adultos de B. tabaci como mecanismo de transporte y dispersi\uf3n de otra plaga pol\uedfaga como P. latus

    Directed paths on hierarchical lattices with random sign weights

    Full text link
    We study sums of directed paths on a hierarchical lattice where each bond has either a positive or negative sign with a probability pp. Such path sums JJ have been used to model interference effects by hopping electrons in the strongly localized regime. The advantage of hierarchical lattices is that they include path crossings, ignored by mean field approaches, while still permitting analytical treatment. Here, we perform a scaling analysis of the controversial ``sign transition'' using Monte Carlo sampling, and conclude that the transition exists and is second order. Furthermore, we make use of exact moment recursion relations to find that the moments always determine, uniquely, the probability distribution $P(J)$. We also derive, exactly, the moment behavior as a function of $p$ in the thermodynamic limit. Extrapolations ($n\to 0$) to obtain for odd and even moments yield a new signal for the transition that coincides with Monte Carlo simulations. Analysis of high moments yield interesting ``solitonic'' structures that propagate as a function of pp. Finally, we derive the exact probability distribution for path sums JJ up to length L=64 for all sign probabilities.Comment: 20 pages, 12 figure

    The Role of Palliative Care Consultation in Withdrawal of Life-Sustaining Treatment among ICU Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): A Retrospective Case-Control Study

    Get PDF
    Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on venovenous ECMO (VV-ECMO) at the intensive care unit (ICU) of a tertiary care hospital. Methods: In a retrospective observational study, electronic medical records of 750 patients admitted to the ICU of our hospital between January 1, 2015, and October 31, 2021, were reviewed. Data was collected for patients on VV-ECMO, for whom WOLST was withdrawn during the ICU stay. Clinical characteristics and the underlying reasons for WOLST were compared between those who received PCC (PCC group) and those who did not (non-PCC group). Results: A total of 95 patients were included in our analysis, 63 in the PCC group and 32 in the non-PCC group. The average age of the study population was 48.8 ± 12.6 years, and 64.2% were male. There was no statistically significant difference between the two groups in terms of demographics or clinical characteristics at the time of ICU admission. The average duration of ICU stay and VV-ECMO were 14.1 ± 19.9 days and 9.4 ± 16.6 days, respectively. The number of PCC visits was correlated with the length of ICU stay. The average duration of ICU stay (40.3 ± 33.2 days vs 27.8 ± 19.3 days, P = .05) and ECMO treatment (31.9 ± 27 days vs 18.6 ± 16.1 days, P = .01) were significantly longer in patients receiving PCC than those not receiving PCC. However, the frequency of life sustaining measures or the underlying reasons for WOLST did not significantly differ between the two groups (P \u3e .05). Conclusion: Among ICU patients requiring ECMO support, longer duration of ICU stay and treatment with a higher number of life-sustaining measures seemed to be correlated with the number of PCC visits. The underlying reasons for WOLST seem not to be affected by PCC

    The Role of Palliative Care Consultation in Withdrawal of Life-Sustaining Treatment among ICU Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): A Retrospective Case-Control Study

    Get PDF
    Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on venovenous ECMO (VV-ECMO) at the intensive care unit (ICU) of a tertiary care hospital. Methods: In a retrospective observational study, electronic medical records of 750 patients admitted to the ICU of our hospital between January 1, 2015, and October 31, 2021, were reviewed. Data was collected for patients on VV-ECMO, for whom WOLST was withdrawn during the ICU stay. Clinical characteristics and the underlying reasons for WOLST were compared between those who received PCC (PCC group) and those who did not (non-PCC group). Results: A total of 95 patients were included in our analysis, 63 in the PCC group and 32 in the non-PCC group. The average age of the study population was 48.8 ± 12.6 years, and 64.2% were male. There was no statistically significant difference between the two groups in terms of demographics or clinical characteristics at the time of ICU admission. The average duration of ICU stay and VV-ECMO were 14.1 ± 19.9 days and 9.4 ± 16.6 days, respectively. The number of PCC visits was correlated with the length of ICU stay. The average duration of ICU stay (40.3 ± 33.2 days vs 27.8 ± 19.3 days, P = .05) and ECMO treatment (31.9 ± 27 days vs 18.6 ± 16.1 days, P = .01) were significantly longer in patients receiving PCC than those not receiving PCC. However, the frequency of life sustaining measures or the underlying reasons for WOLST did not significantly differ between the two groups (P \u3e .05). Conclusion: Among ICU patients requiring ECMO support, longer duration of ICU stay and treatment with a higher number of life-sustaining measures seemed to be correlated with the number of PCC visits. The underlying reasons for WOLST seem not to be affected by PCC

    Factores predisponentes a la parvovirosis canina registrados en un hospital de Cuautitlan, México

    Get PDF
    Canine parvovirus (CPV) was initially described in the Canidae family, but later extended to Ursidae, Procionidae, and Felidae families, among others. Its epidemiology has not been fully described. Nevertheless, climate appears to have a direct influence on the severity of the disease symptomatology. Aim of this study was to analyze the influence of different factors such as age, breed, gender, vaccination status, and climatic variables, by means of analyzing cases of this disease recorded at an veterinary hospital from Cuautitlan (México). For this purpose, clinic histories from 2016 until 2017, were analyzed. Prevalence of 1.86% was determined, being animals under seven months-old those with the highest susceptibility to CPV. In addition, from March to May, the highest number of cases were diagnosed, with peak on April. The environmental temperature explains the higher presentation of cases of parvovirus. Considering these results, it can be concluded that CPV seems to be more frequent during the warmer months, followed by high number of offspring and lower consumption of food.El parvovirus canino (PVC) se restringió inicialmente a infectar a los perros, pero luego seextendió a otras familias como felidae (gatos y otros felinos), procionidae (mapaches, coatíes)y ursidae (osos). A pesar de que su epidemiología no ha sido descrita completamente,el clima parece tener influencia directa en los rangos de presentación. En este trabajo secompararon factores como edad, raza, género, estado vacunal y variables climáticas, conla aparición de la enfermedad en un hospital veterinario de Cuautitlan (México). Mediantela revisión de 3.862 historias clínicas de los años 2016-2017, se encontró una prevalencia de1,86% (72 animales) diagnosticados con PVC, siendo los menores de 7 meses los de mayorsusceptibilidad, especialmente durante los meses de marzo a mayo, con mayor incidencia enabril. La variable aumento de la temperatura ambiental explicó la mayor presentación de laenfermedad, seguida por el sexo hembra, el mayor número de crías, la joven edad y el menorconsumo de alimento

    Brightening of 630.0 nm equatorial spread-F airglow depletions

    Get PDF
    [1] Observations from the Boston University all-sky imaging system at Arecibo, Puerto Rico (18.3°N, 66.7°W, 28°N mag), show an unusual behavior of nighttime 630.0-nm airglow depletions. Associated with equatorial spread-F (ESF), these structures move eastward before reversing their motion and become airglow enhancements. Few other cases have been found, all during December solstices. For the case study presented here, data from the Arecibo incoherent scatter radar and the Republic of China Scientific Satellite (ROCSAT-1) provide supporting information. The radar shows that around local midnight the background zonal and meridional plasma motions reverse to westward and southward, respectively. ROCSAT-1 shows enhanced ion density, i.e., a low-latitude plasma blob, above the bright feature recorded by the all-sky imager, indicating a possible connection between both phenomena. Drifts parallel to the magnetic field are observed only in the region where the enhancement occurs. One possible interpretation of this change in the brightness of the depleted structure involves the influence of northward meridional winds and a reversal in the zonal drift motion, most likely caused by a zonal wind reversal
    • …
    corecore