High viscosity presents a challenge for manufacturing and drug delivery of therapeutic antibodies. The viscosity is determined by protein-protein interactions among many antibodies. Molecular simulation is a promising method to study protein-protein interactions; however, all-atom models do not allow the simulation of multiple molecules, which is necessary to compute viscosity directly. Coarse-grained models, on the other hand can do this. In this work, a 12-bead coarse-grained model based on Swan and coworkers (J. Phys. Chem. B 2018, 122, 2867-2880) was applied to study antibody interactions. Two adjustable parameters related to the short-range interactions on the variable and constant regions were determined by fitting experimental data of 20 IgG1 monoclonal antibodies at 150 mg/mL. The root-mean-square deviation improved from 1 to 0.68, and the correlation coefficient improved from 0.63 to 0.87 compared to that of a previous model that assumed the short-range interactions were the same for all the beads. Our model is also able to calculate the viscosity over a wide range of concentrations without additional parameters. A tabulated viscosity based on our model is provided to facilitate antibody screening in early-stage design.
Recent voices have challenged the Eurocentric gaze in IR . Western hegemony over the discipline has been accounted due to structural, disciplinary, language, institutional reasons, and the monopoly over knowledge production by the West. The big bangs of IR, 1919 and 1648, have played a role in the construction of a Eurocentric IR discipline which is still presumed to be a ‘White man's burden' which needs to theorize the non-West. Conversations within the IR academe to recalibrate IR are incestuous, and the ‘dialogue' is going on within the ‘conclaves' of the various national schools, rather than across the various ‘silos' within the IR community. A more appropriate ‘lens’ to make the study of IR ' Global' would be to adopt an eclectic model and to strengthen perspectives like postcolonialism, Contrapuntal reading, and Marxist perspectives to bridge the gap between the core and the periphery and reign in the silenced narratives.
The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.
Background: Different agents have been used to control postoperative sore throat after general anesthesia with variable success. The aim of this study was to compare the effect of preoperative-nebulized magnesium sulfate versus lidocaine on the prevention of post-intubation sore throat. Methods: A prospective double-blind randomized controlled study. Seventy-eight8 patients were divided randomly into three equal groups: Group (M) (n = 26): received nebulized magnesium sulfate 250 mg (2.5 ml) plus 2.5 ml normal saline. Group (L) (n = 26): received nebulized lidocaine 2% 100 mg (5 ml). Group (C) (n = 26): received nebulized normal saline 5 ml. So total volume (5 ml). Patients nebulized by compressor nebulizing for 15 min before the induction of anesthesia. Results: At 0 and 2 h postoperative, the severity and incidence of sore throat were statistically significantly lower in group M and L compared to the C group (P < 0.001). However, at the same time interval, both groups M and L were comparable (P > 0.05). At 4, 8, 12, 24 h postoperative, the severity and incidence of sore throat were statistically significantly lower in group M compared to L and C groups (P < 0.001). However, at the same time interval, both groups L and C were comparable (P > 0.05). The hemodynamics was statistically significantly reduced in group L compared to M and C groups. However, group M showed statistically insignificant changes in hemodynamics compared to groups L and C. Conclusions: Preoperative 250 mg nebulized magnesium sulfate has more protection against post-intubation sore throat than 100 mg nebulized lidocaine lasting up to 24 h after the operation.
Influence of foliar application of maize grains extract (aqueous and alcoholic) on the nutrient acquisition, osmoprotectants accumulation, ROS-scavenging system, and endogenous phytohormones profile in salt-stressed plants has received no attention. Therefore, the current study, as a first report, was aimed to test the hypothesis that the maize grains extract (MGE) application may give an advantage to overcome salinity problems by altering these mechanisms. Phaseolus vulgaris L., cv. Paulista plants were grown in salty soils (EC = 7.43-7.51 dS m(-1)) with and without MGE applications as follows: both seeds and plants were treated by distilled water (MGE0), seeds soaked in MGE and plants sprayed with distilled water (MGEseeds), seeds soaked in distilled water and plants sprayed with MGE (MGEplants), as well as both seeds and plants were treated by MGE (MGEboth). MGE treatments protected plants against the deleterious effects of saline condition by improving growth and yield components, relative water content, membrane stability index, photosynthetic pigments content, soluble sugars, proline, N, P, K+, Ca2+, indole-3-acetic acid, gibberellic acid, cytokinins concentrations, K+/Na+ and Ca2+/Na+ ratios, superoxide dismutase, catalase, peroxidase activities, and glutathione, ascorbate contents. Therefore, MGE as environmental-friendly, sustainable and efficient strategy can reprogramme plant responses to mitigate the adverse effects of salinity stress.
Background: This exploratory study aimed to characterize the gut microbiome of individuals with different periodontal conditions, and correlate it with periodontal inflammation and tissue destruction. Methods: Stool samples were obtained from individuals presenting periodontal health (PH = 7), gingivitis (G = 14) and chronic periodontitis (CP = 23). The intestinal microbiome composition was determined by Illumina MiSeq sequencing. Results: A lower alpha-diversity in the gut microbiome of individuals with CP was observed, although no significant difference among groups was found (p > 0.01). Firmicutes, Proteobacteria, Verrucomicrobia and Euryarchaeota were increased, whereas Bacteroidetes were decreased in abundance in patients with periodontitis compared to PH. Prevotella (genus), Comamonadaceae (family) and Lactobacillales (order) were detected in higher numbers in G, while Bacteroidales (order) was predominant in PH (p < 0.01). Significant correlations (rho = 0.337-0.468, p < 0.01) were found between OTUs representative of periodontal pathogens and attachment loss. Mogibacteriaceae, Ruminococcaceae and Prevotella were able to discriminate individuals with periodontal diseases from PH (overall accuracy = 84%). Oral taxa were detected in high numbers in all stool samples. Conclusions: Individuals with periodontal diseases present a less diverse gut microbiome consistent with other systemic inflammatory diseases. High numbers of oral taxa related to periodontal destruction and inflammation were detected in the gut microbiome of individuals regardless of periodontal status.
We compare approaches to measure oxygen surface exchange kinetics, by simultaneous optical transmission relaxation (OTR) and AC-impedance spectroscopy (AC-IS), on the same mixed conducting SrTi0.65Fe0.35O3-x film. Surface exchange coefficients were evaluated as a function of oxygen activity in the film, controlled by gas partial pressure and/or DC bias applied across the ionically conducting yttria-stabilized zirconia substrate. Changes in measured light transmission through the film over time (relaxations) resulted from optical absorption changes in the film corresponding to changes in its oxygen and oxidized Fe (~Fe4+) concentrations; such relaxation profiles were successfully described by the equation for surface exchange-limited kinetics appropriate for the film geometry. The kchem values obtained by OTR were significantly lower than the AC-IS derived kchem values and kq values multiplied by the thermodynamic factor (bulk or thin film), suggesting a possible enhancement in k by the metal current collectors (Pt, Au). Long-term degradation in kchem and kq values obtained by AC-IS was also attributed to deterioration of the porous Pt current collector, while no significant degradation was observed in the optically derived kchem values. The results suggest that, while the current collector might influence measurements by AC-IS, the OTR method offers a continuous, in situ, and contact-free method to measure oxygen exchange kinetics at the native surfaces of thin films.
Federal spending on non-health entitlement programs, including the Earned Income Tax Credit and SNAP, has decreased as a percent of GDP since 2011, putting social safety net and community and economic development funding at risk. As an important component of community development, small business support programs are also at risk under social spending cuts. While theory suggests that a strong small business sector could protect health by improving socioeconomic conditions and reducing unemployment, the public health implications of reduced support for small business has not been explored. We conducted a scoping literature review of studies indexed by Pubmed, Cochrane Review, Google Scholar, and Academic Search Premier. The literature suggests that small businesses may provide social and economic benefits to communities that likely protect health, especially in economically deprived communities. These health impacts should be considered when policy-makers weigh decisions that affect small businesses and funding for community and economic development.
This article discusses and highlights alignment issues that arise between UNIMARC Authorities Format and Resource Description and Access (RDA) regarding the creation of name and title authorities for musical works and creators. More specifically, RDA, as an implementation of the FRAD model, is compared with the UNIMARC Authorities Format (Updates 2012 and 2016) in an effort to highlight various cases where the discovery of equivalent fields between the two standards is not obvious. The study is envisioned as a first step in an ongoing process of working with the UNIMARC community throughout RDA's advancement and progression regarding the entities [musical] Work and Names.
The deployment of gene drives is emerging as an alternative for protecting endangered species, controlling agricultural pests, and reducing vector-borne diseases. This paper reports on a workshop held in February 2016 to explore the complex intersection of political, economic, ethical, and ecological risk issues associated with gene drives. Workshop participants were encouraged to use systems thinking and mapping to describe the connections among social, policy, economic, and ecological variables as they intersect within governance systems. In this paper, we analyze the workshop transcripts and maps using the Institutional Analysis and Development (IAD) framework to categorize variables associated with gene drive governance and account for the complexities of socio-ecological systems. We discuss how the IAD framework can be used in the future to test hypotheses about how features of governance systems might lead to certain outcomes and inform the design of research programs, public engagement, and anticipatory governance of gene drives.
By performing nine genome-wide microRNA (miRNA) screens, we recently uncovered a new class of miRNAs, which target multiple cyclins and cyclin-dependent kinases (CDKs). Systemic delivery of selected cell cycle-targeting miRNAs to mouse xenograft models resulted in potent anti-tumorigenic effects without affecting animals' health. Here, we provide an in-depth description of our miRNA screening methodology, analyses of selected cell cycle-targeting miRNAs, and discuss why miRNA therapy might be a viable therapeutic option for cancer patients.
Using duplex-consensus sequencing technology, we recently identified the characteristic high-resolution mutational spectrum of the liver carcinogen aflatoxin B1 in a mouse model, many months before aflatoxin-induced tumors are detectable. The diagnostic power of this spectrum is then demonstrated by accurately identifying, among the sequenced human liver tumors, the subset of cancers associated with aflatoxin B1 exposure.
The A1Π(v = 0) level of 12C18O has been reinvestigated using three different high-resolution spectroscopic methods: (1) 2 + 1′ resonance-enhanced multiphoton ionisation of the A1Π − X1Σ+(0, 0) band using narrowband lasers in a Doppler-free geometry; (2) Fourier-transform emission spectroscopy in the visible range probing the B1Σ+ − A1Π(0, 0) band in a discharge; (3) Fourier-transform absorption spectroscopy in the vacuum-ultraviolet range measuring the A1Π − X1Σ+(0, 0) and B1Σ+ − X1Σ+(0, 0) bands at multiple temperatures ranging from 90 to 900 K. An effective-Hamiltonian analysis of A1Π, v = 0 levels was performed up to J = 44 which quantitatively addresses perturbations by the e 3Σ−(v = 1), d3Δ(v = 4), a′3Σ+(v = 9), D 1Δ(v = 0), and I 1Σ−(v = 0, 1) levels.
