Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy.

There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.JS and JAZ would like to acknowledge the UK Engineering and Physical Sciences Research Council for funding (EP/J007803/1).This is the final version of the article. It first appeared from ACS at http://dx.doi.org/10.1021/acs.molpharmaceut.5b0033

Properties of a Yeast Cytochrome P-450-Containing Enzyme System which Catalyzes the Hydroxylation of Fatty Acids, Alkanes, and Drugs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65977/1/j.1432-1033.1973.tb02948.x.pd

Measurement of the Stress State in the Lower Link of the Three-Point Hitch Mechanism

Agricultural machines and their implements are subjected to dynamic loads during farm operations. Depending on the type of operation (e.g. lifting or plowing), lower links of the three-point hitch mechanism are exposed to stresses caused by combination of bending moments and axial forces. In this paper we analyzed influence of the soil resistance during plowing in the lower link and the possibility of its failure. The stresses were measured using strain gauges at locations with uniform stress distribution in order to enable more reliable comparison with finite element analysis (FEA). Recorded stresses vs. time were used for identifying mean stresses and amplitudes for different plowing depth and different tractor speeds. Due to the geometry of the lower links and their joints in the three-point hitch mechanism, during plowing and transferring soil resistance, links are loaded not only by axial forces but also by bending moment in the horizontal plane. Under some assumptions, FEA provided us to make relations between the measured stresses and the loads that caused them. Measured stresses show that links have significant safety margin relative to tractor installed power and soil resistance, which enables the possibility of their design optimization. Obtained results may also serve for further analyses of fatigue life prediction, measurement of the draft forces etc

Fig 4 -

(A) Clustering results with t-distributed stochastic neighbor embedding (t-SNE2) plot (N = 1,957). A t-SNE2 plot embeds high-dimensional data to allow visualization in two-dimensional space. (B) Proportion of people reporting difficulty with falling in each cluster. Error bars indicate Bonferroni-adjusted confidence intervals. (C) Summary of the fall-related factors for the three clusters. Darker boxes indicate variables associated with lower likelihood of reporting difficulty with falling, and vice versa. The first three columns include the fall-related factors that had monotonic differences across clusters that were parallel to the difference in reporting with difficulty with falling. In the remaining four columns, the differences were not parallel. Mean values shown in brackets for physical activity (PA), age, and body mass index (BMI). Male: Female is the ratio of males to females; vision/cognitive/balance is a qualitative combination of the three factors.</p

Means and proportions of the fall-related factors, expressed for all data combined, and for each cluster.

Numeric scores are reported as means, categorical scores are proportions (prop.), as indicated with each variable. P-values are Benjamini-Hochberg adjusted (allows for a 5% false discovery rate). Post hoc analyses to compare clusters were Bonferroni adjusted (p = 0.0167); significant post hocs are noted with an asterisk for each cluster comparison (cluster 1 versus 2 = 1 v 2, etc.). ‘Likert’ indicates Likert scale from 1–4 with 1 = no difficulty and 4 = unable.</p

Bivariate associations between the 20 fall-related factors (listed on the left) and reporting difficulty with falling (N = 1,957).

A logistic regression (and corresponding Wald-test) was conducted between each fall-related factor and reporting difficulty with falling. Odds ratio (95% Wald confidence intervals). All odds ratios were significant (p≤0.02) with the following exceptions: race, BMI, and cancer (p≥0.08). PA = physical activity. † dichotomous variables. For continuous and integer variables, each unit corresponds to the unit of measurement (e.g., one unit of age is one year, one unit of 20 ft walk test is one second), with the following exceptions: ‡ for cognitive function, one unit is five points on Digit Symbol Substitution Test (max score 133). § for balance, one unit is 10 s during the Romberg test of standing balance (max score 90 s). †† for PA, one unit is 30 minutes of PA. ‡‡ for visual acuity, one unit is 10 ft in the denominator of the visual acuity score (e.g., 20/20 to 20/30). §§ Likert scale 1–4, one unit is one integer on the scale.</p

Fig 3 -

(A) Frequency histogram for the number of fall-related factors for all participants (N = 1,957). (B) Proportion of participants reporting difficulty with falling as a function of the number of fall-related factors. Error bars indicate Bonferroni-adjusted confidence intervals; confidence intervals were not calculated when the number of risk factors was greater than 11 due to the low numbers of participants in those categories.</p

Participants flow diagram.

MVPA: Moderate-to-vigorous physical activity. PA: physical activity.</p