scholarly journals Co-Amorphization of Kanamycin with Amino Acids Improves Aerosolization

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 715 ◽  
Author(s):  
Bishal Raj Adhikari ◽  
Kārlis Bērziņš ◽  
Sara J. Fraser-Miller ◽  
Keith C. Gordon ◽  
Shyamal C. Das
Keyword(s):  
Amino Acids ◽  
Physical Stability ◽  
Low Frequency ◽  
Principal Component ◽  
Underlying Mechanism ◽  
High Dose ◽  
Particle Fraction ◽  
Dry Powders ◽  
Model Drug ◽  
Thermal Technique

Different formulation techniques have been investigated to prepare highly aerosolizable dry powders to deliver a high dose of antibiotics to the lung for treating local infections. In this study, we investigated the influence of the co-amorphization of a model drug, kanamycin, with selected amino acids (valine, methionine, phenylalanine, and tryptophan) by co-spray drying on its aerosolization. The co-amorphicity was confirmed by thermal technique. The physical stability was monitored using low-frequency Raman spectroscopy coupled with principal component analysis. Except for the kanamycin-valine formulation, all the formulations offered improved fine particle fraction (FPF) with the highest FPF of 84% achieved for the kanamycin-methionine formulation. All the co-amorphous formulations were physically stable for 28 days at low relative humidity (25 °C/<15% RH) and exhibited stable aerosolization. At higher RH (53%), even though methionine transformed into its crystalline counterpart, the kanamycin-methionine formulation offered the best aerosolization stability without any decrease in FPF. While further studies are warranted to reveal the underlying mechanism, this study reports that the co-amorphization of kanamycin with amino acids, especially with methionine, has the potential to be developed as a high dose kanamycin dry powder formulation.

Chemical Fingerprint Analysis and Simultaneous Determination of Nucleosides and Amino Acids in Kang Fu Xin Liquid by High Performance Liquid Chromatography with Diode Array Detector

2020 ◽  
Vol 16 (7) ◽  
pp. 831-843
Author(s):  
Yuwen Wang ◽  
Shuping Li ◽  
Liuhong Zhang ◽  
Shenglan Qi ◽  
Huida Guan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Quality Control ◽  
Uric Acid ◽  
Control Method ◽  
Principal Component ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Fingerprint Analysis ◽  
Wavelength Switching

Background and Objective: Kang Fu Xin liquid (KFX) is an official preparation made from the ethanol extract product from P. Americana. The present quality control method cannot control the quality of the preparation well. The aim of the present study is to establish a convenient HPLC method for multicomponents determination combined with fingerprint analysis for quality control of KFX. Methods: An HPLC-DAD method with gradient elution and detective wavelength switching program was developed to establish HPLC fingerprints of KFX, and 38 batches of KFX were compared and evaluated by similarity analysis (SA), hierarchical clustering analysis (HCA), and principal component analysis (PCA). Meanwhile, six nucleosides and three amino acids, including uracil, hypoxanthine, uric acid, adenosine, xanthine, inosine, tyrosine, phenylalanine and tryptophan in KFX were determined based on the HPLC fingerprints. Results: An HPLC method assisted with gradient elution and wavelength switching program was established and validated for multicomponents determination combined with fingerprint analysis of KFX. The results demonstrated that the similarity values of the KFX samples were more than 0.845. PCA indicated that peaks 4 (hypoxanthine), 7 (xanthine), 9 (tyrosine), 11, 13 and 17 might be the characteristic contributed components. The nine constituents in KFX, uracil, hypoxanthine, uric acid, adenosine, xanthine, inosine, tyrosine, phenylalanine and tryptophan, showed good regression (R2 > 0.9997) within test ranges and the recoveries of the method for all analytes were in the range from 96.74 to 104.24%. The limits of detections and quantifications for nine constituents in DAD were less than 0.22 and 0.43 μg•mL-1, respectively. Conclusion: The qualitative analysis of chemical fingerprints and the quantitative analysis of multiple indicators provide a powerful and rational way to control the KFX quality for pharmaceutical companies.

scholarly journals Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 388
Author(s):  
Minghua Tang ◽  
Nicholas E. Weaver ◽  
Lillian M. Berman ◽  
Laura D. Brown ◽  
Audrey E. Hendricks ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dietary Intervention ◽  
Principal Component ◽  
Essential Amino Acids ◽  
Infant Growth ◽  
Serum Samples ◽  
Z Scores ◽  
Protein Rich ◽  
Over Time ◽  
Complementary Diet

Background: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. Results: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.

scholarly journals Complex Principal Component Analysis of Antarctic Ice Sheet Mass Balance

2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Jingang Zhan ◽  
Hongling Shi ◽  
Yong Wang ◽  
Yixin Yao
Keyword(s):  
Principal Component Analysis ◽  
Ice Sheet ◽  
Low Frequency ◽  
Principal Component ◽  
Equatorial Pacific ◽  
Mass Change ◽  
Frequency Variation ◽  
Periodic Signal ◽  
Time Frequency ◽  
The Antarctic

Ice sheet changes of the Antarctic are the result of interactions among the ocean, atmosphere, and ice sheet. Studying the ice sheet mass variations helps us to understand the possible reasons for these changes. We used 164 months of Gravity Recovery and Climate Experiment (GRACE) satellite time-varying solutions to study the principal components (PCs) of the Antarctic ice sheet mass change and their time-frequency variation. This assessment was based on complex principal component analysis (CPCA) and the wavelet amplitude-period spectrum (WAPS) method to study the PCs and their time-frequency information. The CPCA results revealed the PCs that affect the ice sheet balance, and the wavelet analysis exposed the time-frequency variation of the quasi-periodic signal in each component. The results show that the first PC, which has a linear term and low-frequency signals with periods greater than five years, dominates the variation trend of ice sheet in the Antarctic. The ratio of its variance to the total variance shows that the first PC explains 83.73% of the mass change in the ice sheet. Similar low-frequency signals are also found in the meridional wind at 700 hPa in the South Pacific and the sea surface temperature anomaly (SSTA) in the equatorial Pacific, with the correlation between the low-frequency periodic signal of SSTA in the equatorial Pacific and the first PC of the ice sheet mass change in Antarctica found to be 0.73. The phase signals in the mass change of West Antarctica indicate the upstream propagation of mass loss information over time from the ocean–ice interface to the southward upslope, which mainly reflects ocean-driven factors such as enhanced ice–ocean interaction and the intrusion of warm saline water into the cavities under ice shelves associated with ice sheets which sit on retrograde slopes. Meanwhile, the phase signals in the mass change of East Antarctica indicate the downstream propagation of mass increase information from the South Pole toward Dronning Maud Land, which mainly reflects atmospheric factors such as precipitation accumulation.

scholarly journals Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

scholarly journals Fluctuating Asymmetry and Sexual Dimorphism in Human Facial Morphology: A Multi-Variate Study

Symmetry ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 304
Author(s):  
Omid Ekrami ◽  
Peter Claes ◽  
Ellen Van Assche ◽  
Mark D. Shriver ◽  
Seth M. Weinberg ◽  
...  
Keyword(s):  
Fluctuating Asymmetry ◽  
Life History Traits ◽  
Principal Component ◽  
Underlying Mechanism ◽  
High Density ◽  
Direct Result ◽  
Facial Morphology ◽  
Strongly Correlated ◽  
Large Dataset ◽  
Genetic Quality

(1) Background: Fluctuating asymmetry is often used as an indicator of developmental instability, and is proposed as a signal of genetic quality. The display of prominent masculine phenotypic features, which are a direct result of high androgen levels, is also believed to be a sign of genetic quality, as these hormones may act as immunosuppressants. Fluctuating asymmetry and masculinity are therefore expected to covary. However, there is lack of strong evidence in the literature regarding this hypothesis. (2) Materials and methods: In this study, we examined a large dataset of high-density 3D facial scans of 1260 adults (630 males and 630 females). We mapped a high-density 3D facial mask onto the facial scans in order to obtain a high number of quasi-landmarks on the faces. Multi-dimensional measures of fluctuating asymmetry were extracted from the landmarks using Principal Component Analysis, and masculinity/femininity scores were obtained for each face using Partial Least Squares. The possible correlation between these two qualities was then examined using Pearson’s coefficient and Canonical Correlation Analysis. (3) Results: We found no correlation between fluctuating asymmetry and masculinity in men. However, a weak but significant correlation was found between average fluctuating asymmetry and masculinity in women, in which feminine faces had higher levels of fluctuating asymmetry on average. This correlation could possibly point to genetic quality as an underlying mechanism for both asymmetry and masculinity; however, it might also be driven by other fitness or life history traits, such as fertility. (4) Conclusions: Our results question the idea that fluctuating asymmetry and masculinity should be (more strongly) correlated in men, which is in line with the recent literature. Future studies should possibly focus more on the evolutionary relevance of the observed correlation in women.

scholarly journals Roles of the C-Terminal Amino Acids of Non-Hexameric Helicases: Insights from Escherichia coli UvrD

2021 ◽  
Vol 22 (3) ◽  
pp. 1018
Author(s):  
Hiroaki Yokota
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Single Molecule ◽  
Underlying Mechanism ◽  
Amino Acid Sequences ◽  
E Coli ◽  
X Ray Crystallography ◽  
Terminal Amino

Helicases are nucleic acid-unwinding enzymes that are involved in the maintenance of genome integrity. Several parts of the amino acid sequences of helicases are very similar, and these quite well-conserved amino acid sequences are termed “helicase motifs”. Previous studies by X-ray crystallography and single-molecule measurements have suggested a common underlying mechanism for their function. These studies indicate the role of the helicase motifs in unwinding nucleic acids. In contrast, the sequence and length of the C-terminal amino acids of helicases are highly variable. In this paper, I review past and recent studies that proposed helicase mechanisms and studies that investigated the roles of the C-terminal amino acids on helicase and dimerization activities, primarily on the non-hexermeric Escherichia coli (E. coli) UvrD helicase. Then, I center on my recent study of single-molecule direct visualization of a UvrD mutant lacking the C-terminal 40 amino acids (UvrDΔ40C) used in studies proposing the monomer helicase model. The study demonstrated that multiple UvrDΔ40C molecules jointly participated in DNA unwinding, presumably by forming an oligomer. Thus, the single-molecule observation addressed how the C-terminal amino acids affect the number of helicases bound to DNA, oligomerization, and unwinding activity, which can be applied to other helicases.

scholarly journals Effect of Time and Legume Type on Germination-Induced Proteolysis of Lentils and Faba Beans

Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 4
Author(s):  
Sara Bautista-Expósito ◽  
Elena Peñas ◽  
Albert Vanderberg ◽  
Juana Frias ◽  
Cristina Martínez-Villaluenga
Keyword(s):  
Amino Acids ◽  
Protease Activity ◽  
Protein Quality ◽  
Principal Component ◽  
Fold Increase ◽  
Protein Digestibility ◽  
Essential Amino Acids ◽  
Seedling Development ◽  
Positive Effects ◽  
Faba Beans

Legumes are alternative protein sources that have been successfully used to develop diverse meatless foods. Although these plant-based products have a lower impact on the environment than equivalent animal-based products, they have lower protein digestibility. Germination could be a useful bioprocess to enhance protein digestibility in legumes, although its effect at different times of seedling development has been little studied in lentils and faba beans. This work investigated the effect of germination time (4 and 6 days after full seed imbibition) on the proteins of three types of Canadian lentils (“gray zero tannin”, G; “caviar black”, B; and “red dehulled”, D) and faba beans (“zero vicin/convicin”, F). Germination increased total nitrogen (4–14% increase) and total levels of some amino acids: Asp in all the sprouts studied; Ser, Pro, Ala, Cys, His and Lys in G; and Met and Tyr in B. A concurrent degradation of the 7S and 11S globulin subunits, the accumulation of peptides below 20 kDa and free essential and non-essential amino acids (4- to 6-fold increase) were observed after germination in all the legumes studied. These effects were attributable to the increased protease activity observed after sprouting. Trypsin inhibitory activity was lower in legume sprouts, except for D, where a small increase was detected. Time, legume type and their interaction showed significant effects on the parameters studied. Germination effects were generally more remarkable at longer stages of seedling development. Among the legumes studied, D showed a differential behavior characterized by a faster protein degradation and release of small peptides, probably due to its higher protease activity as indicated by principal component analysis. These results evidence the positive effects of germination on the protein digestibility of different lentil types and faba beans. The protein quality of plant-based foods could be improved through the selection of legume species with higher germination-induced proteolytic rates and optimized germination times.

Low frequency vibrational spectra of some amino acids

1998 ◽  
Vol 450 (1-3) ◽  
pp. 121-128 ◽  
Author(s):  
G. Dovbeshko ◽  
L. Berezhinsky
Keyword(s):  
Amino Acids ◽  
Vibrational Spectra ◽  
Low Frequency

222 Corn-expressed Phytase Modulates Serum Amino Acids and Proteomics Profiles in Nursery Pigs Fed with Low-protein, -calcium, and -phosphorous Diets

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Cedrick N N Shili ◽  
Mohammad Habibi ◽  
Parniyan Goodarzi ◽  
Frank Kiyimba ◽  
Steve Hartsen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Performance ◽  
Growth Regulation ◽  
Serum Proteins ◽  
Bone Mineralization ◽  
Negative Control ◽  
Differentially Expressed ◽  
High Dose ◽  
Blood Proteins ◽  
Low Protein

Abstract Feeding pigs with very low-protein (VLP) and low-phosphorous (P) diets may be useful for decreasing the nutrients excretion to the environment; however, this practice negatively impacts the animals’ growth performance. A beneficial effect of corn-expressed phytase (CEP) on growth performance of pigs fed with VLP diets was shown by our group recently. Little is known whether this improvement is related with alterations in profile of blood proteins and amino acids (AA). The objective of this study was to investigate whether supplementation of VLP, low-calcium (Ca) and low-P diets with a CEP can influence the serum AA and proteomics profiles in pigs. Forty-eight weaned barrows were subjected into one of the following groups (n = 8/group) for 4 weeks: positive control (PC), negative control-reduced protein (NC), NC+low-dose CEP, i.e 2,000 FTU/kg (LD), NC+high-dose CEP, i.e. 4,000 FTU/kg (HD), LD with reduced Ca/P (LDR), and HD with reduced Ca/P (HDR). At week 4, blood samples were collected from all pigs. Compared to PC, NC reduced the serum leucine and phenylalanine concentrations; however, LD recovered their levels. Using trypsinolysis and mass spectrometry, 703 serum proteins were identified and quantified, wherein 25 were found to be differentially expressed among groups. Hierarchical clustering showed a clear separation in proteins identified among dietary groups. Compared to NC, 23 and 24 proteins were found to be differentially expressed in serum of LD and HD groups, respectively, with some important proteins in growth regulation such as SELENOP being upregulated and the IGFBP family being downregulated in these groups. A positive correlation was detected between growth and abundance of BGN, TLN1, PDLIM1 and COL1A2 that are involved in bone mineralization and muscle structure development. Thus, CEP improved the serum profile of some essential AA and affected the expression of proteins involved in regulation of growth in pigs fed with VLP diets.

Assessment of Damage Progression in Automotive Electronics Assemblies Subjected to Temperature and Vibration

2018 ◽  
Author(s):  
Pradeep Lall ◽  
Tony Thomas
Keyword(s):  
Instantaneous Frequency ◽  
Low Frequency ◽  
Principal Component ◽  
Large Data ◽  
Data Sets ◽  
Automotive Electronics ◽  
Damage Progression ◽  
Mode Decomposition ◽  
Electronic Assemblies ◽  
Strain Signal

Electronics in automotive underhood environments is used for a number of safety critical functions. Reliable continued operation of electronic safety systems without catastrophic failure is important for safe operation of the vehicle. There is need for prognostication methods, which can be integrated, with on-board sensors for assessment of accrued damage and impending failure. In this paper, leadfree electronic assemblies consisting of daisy-chained parts have been subjected to high temperature vibration at 5g and 155°C. Spectrogram has been used to identify the emergence of new low frequency components with damage progression in electronic assemblies. Principal component analysis has been used to reduce the dimensionality of large data-sets and identify patterns without the loss of features that signify damage progression and impending failure. Variance of the principal components of the instantaneous frequency has been shown to exhibit an increasing trend during the initial damage progression, attaining a maximum value and decreasing prior to failure. The unique behavior of the instantaneous frequency over the period of vibration can be used as a health-monitoring feature for identifying the impending failures in automotive electronics. Further, damage progression has been studied using Empirical Mode Decomposition (EMD) technique in order to decompose the signals into Independent Mode Functions (IMF). The IMF’s were investigated based on their kurtosis values and a reconstructed strain signal was formulated with all IMF’s greater than a kurtosis value of three. PCA analysis on the reconstructed strain signal gave better patterns that can be used for prognostication of the life of the components.

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