Continuous manufacturing is an important element of future manufacturing solutions enabling for both high product quality and streamlined development process. The increasing possibilities with computer simulations allow for innovating novel mixing principles applicable for continuous manufacturing. However, these innovative ideas based on simulations need experimental validation. The use of rapid prototyping based on additive manufacturing opens a possibility to evaluate these ideas at a low cost. In this study, a novel powder mixing geometry was prototyped using additive manufacturing and further, interfaced with an in-line near-IR spectrometer allowing for investigating the residence time distribution (RTD) in this geometry.

Successful implementation of continuous manufacturing processes requires robust methods to assess and control product quality in a real-time mode. In this study, the residence time distribution of a continuous powder mixing process was investigated via pulse tracer experiments using near infrared spectroscopy for tracer detection in an in-line mode. The residence time distribution was modeled by applying the continuous stirred tank reactor in series model for achieving the tracer (paracetamol) concentration profiles. Partial least squares discriminant analysis and principal component analysis of the near infrared spectroscopy data were applied to investigate both supervised and unsupervised chemometric modeling approaches. Additionally, the mean residence time for three powder systems was measured with different process settings. It was found that a significant change in the mean residence time occurred when comparing powder systems with different flowability and mixing process settings. This study also confirmed that the partial least squares discriminant analysis applied as a supervised chemometric model enabled an efficient and fast estimate of the mean residence time based on pulse tracer experiments.

Concentrated dairy products are of increasing interest within the dairy industry. Skim milk concentrates can be produced by reverse osmosis membrane filtration, which can be considered a non-thermal process. Therefore, the physical properties of concentrates differ from the properties of concentrates produced by evaporation. In this study, reverse osmosis filtration of raw and pasteurised skim milk was carried out in batch up to 28% total solids content and the effect of thermal treatment (65-110 degrees C, 15 s) and storage at 5 degrees C up to ten days on rheological and physical properties of concentrates, were evaluated. Concentrates produced from pasteurised skim milk required longer concentration times and showed larger average casein micelle sizes, but limited structure buildup capability during storage compared to concentrates produced from raw milk which more readily created structural networks between the milk constituents and consequently had higher viscosity. Thermal treatment of concentrates increased their average particle size and viscosity, an effect enhanced by increasing the total solids content. Concentrates produced from non-pasteurised milk showed the strongest shear-thinning behaviour during storage. Thus, the thermal treatment of milk before or after the concentration process, controls the structure formation of skim milk concentrates during storage.

Near infrared (NIR) spectroscopy is a well-established method for analysis of pharmaceutical products, and especially useful for process monitoring and control of continuous production due to high sample throughput. In this work, a previously established method called empirical target distribution optimization (ETDO) wherein reference sample values using information from model prediction of the calibration data was used as a tool to improve the performance of NIR partial least squares (PLS) models. Model performance was assessed using root mean square error (R2), bias and accuracy in prediction of test samples. A target value selection threshold was tested to assess the ETDO procedure for NIR analysis of powder samples. The amount of specific variation captured by the model was examined and compared for models calibrated with and without ETDO. The results reported in this work suggests that PLS models optimized with ETDO of reference values can provide more specific PLS models for NIR analysis for complex powder mixtures. In addition, the model optimization method could also be applied as a tool to verify the necessary amount of PLS components to produce robust models. The ETDO method presented in this work is an approach that could be applied in the development of continuous blending or tableting processes where robust in-line quantitative analysis of powder samples is needed.

Powder flow in small-scale equipment is challenging to predict. To meet this need, the impact of consolidation during powder flow characterization, the level of consolidation existing during discharge of powders from a tablet press hopper and the uncertainty of shear and wall friction measurements at small consolidation stresses were investigated. For this purpose, three grades of microcrystalline cellulose were used. Results showed that powder flow properties depend strongly on the consolidation during testing. The consolidation during discharge in terms of the major principal stress and wall normal stress were approximately 200 Pa and 114 Pa, respectively, in the critical transition from the converging to the lower vertical section of the hopper. The lower limit of consolidation for the shear and wall friction test was approximately 500 Pa and 200 Pa, respectively. At this consolidation level, the wall and shear stress resolution influences the precision of the measured powder flow properties. This study highlights the need for an improved experimental setup which would be capable of measuring the flow properties of powders under very small consolidation stresses with a high shear stress resolution. This will allow the accuracy, precision and applicability of the shear test to be improved for pharmaceutical applications.

When using shear testing to determine wall friction of pharmaceutical particulate systems, it is crucial to measure at the correct wall normal stress. By comparing data obtained at a wall normal stress of 1000 to 200 Pa, the effect of the applied stress on the accuracy and precision of the method was assessed.

Introduction: We examined short‐term (3‐hour) and long‐term (12‐week) training effects after heavy load [HL; 70% 1RM] and light load (LL; 16% 1RM) exercise. Methods: mRNA expression of genes involved in skeletal muscle remodeling were analyzed and muscle activity (EMG measurements) was measured. Results: Relative muscle activity differed between HL and LL resistance exercise, whereas median power frequency was even, suggesting an equal muscle‐fiber‐type recruitment distribution. mRNA expression of Myf6, myogenin, and p21 was mostly increased, and myostatin was mostly depressed by HL resistance exercise. No major differences were seen in atrophy‐related genes between HL and LL resistance exercise. No changes were seen over 12‐week training for any of the targets. Conclusions: Resistance exercise at LL and HL elevated the expression of genes involved in skeletal muscle hypertrophy, although the greatest response was from HL. However, no long‐term effect from either LL or HL resistance exercise was seen on basal levels of the mRNA targets. Muscle Nerve 47: 748–759, 2013

There is strong evidence for enhanced numbers of satellite cells with heavy resistance training. The satellite cell response to very light muscle loading is, however, unknown. We, therefore, designed a 12‐week training protocol where volunteers trained one leg with a high load (H) and the other leg with a light load (L). Twelve young healthy men [mean age 25 ± 3 standard deviation (SD) years] volunteered for the study. Muscle biopsies were collected from the m. vastus lateralis of both legs before and after the training period and satellite cells were visualized by CD56 immunohistochemistry. A significant main effect of time was observed (P<0.001) for the number of CD56+ cells per fiber (L: from 0.11 ± 0.02 to 0.13 ± 0.03; H: from 0.12 ± 0.03 to 0.15 ± 0.05, mean ± SD). The finding that 12 weeks of training skeletal muscle even with very light loads can induce an increase in the number of satellite cells reveals a new aspect of myogenic precursor cell activation and suggests that satellite cells may play a role in skeletal muscle adaptation over a broad physiological range.

Muscle mass accretion is accomplished by heavy-load resistance training. The effect of light-load resistance exercise has been far more sparsely investigated with regard to potential effect on muscle size and contractile strength. We applied a resistance exercise protocol in which the same individual trained one leg at 70% of one-repetition maximum (1RM) (heavy load, HL) while training the other leg at 15.5% 1RM (light load, LL). Eleven sedentary men (age 25 +/- 1 yr) trained for 12 wk at three times/week. Before and after the intervention muscle hypertrophy was determined by magnetic resonance imaging, muscle biopsies were obtained bilaterally from vastus lateralis for determination of myosin heavy chain (MHC) composition, and maximal muscle strength was assessed by 1RM testing and in an isokinetic dynamometer at 60 degrees /s. Quadriceps muscle cross-sectional area increased (P < 0.05) 8 +/- 1% and 3 +/- 1% in HL and LL legs, respectively, with a greater gain in HL than LL (P < 0.05). Likewise, 1RM strength increased (P < 0.001) in both legs (HL: 36 +/- 5%, LL: 19 +/- 2%), albeit more so with HL (P < 0.01). Isokinetic 60 degrees /s muscle strength improved by 13 +/- 5% (P < 0.05) in HL but remained unchanged in LL (4 +/- 5%, not significant). Finally, MHC IIX protein expression was decreased with HL but not LL, despite identical total workload in HL and LL. Our main finding was that LL resistance training was sufficient to induce a small but significant muscle hypertrophy in healthy young men. However, LL resistance training was inferior to HL training in evoking adaptive changes in muscle size and contractile strength and was insufficient to induce changes in MHC composition.

physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a publishes original papers that deal with diverse area of research in applied

Satellite cells increase in number with heavy resistance training, but the response to very light muscle loading is unknown. We recruited 12 young healthy male (mean age 25 ± SD 3 yrs) volunteers to train one leg with a heavy load (H) and the other leg with a light load (L), for 12 weeks. We hypothesized that, compared to L training, H training would induce a greater response of the satellite cell pool. Satellite cells were visualised by immunohistochemistry on muscle biopsies collected from the m. vastus lateralis of both legs before and after the training period. Compared to the pre training values, there was a significant increase in the number of NCAM+ cells (per myonuclear number) post training in both groups (H: from 4.16 ± 1.01 to 5.32 ± 1.22; L: from 4.01 ± 0.78 to 4.72 ± 1.72; mean ± SD, p < 0.05). The finding that 12 weeks of training skeletal muscle with very low loads can induce an increase in the number of satellite cells reveals a new aspect of myogenic precursor cell activation. This knowledge could be relevant in considering training regimens where heavy resistance training is not possible.Funded by Lundbeck Foundation and the Danish National Research Foundation.

AIM:To examine if cross-sectional area (CSA) differs along the length of the human patellar tendon (PT), and if there is PT hypertrophy in response to resistance training.METHODS:Twelve healthy young men underwent baseline and post-training assessments. Maximal isometric knee extension strength (MVC) was determined unilaterally in both legs. PT CSA was measured at the proximal-, mid- and distal PT level and quadriceps muscle CSA was measured at mid-thigh level using magnetic resonance imaging. Mechanical properties of the patellar tendons were determined using ultrasonography. Subsequently, subjects performed 12 weeks of heavy resistance knee extension training with one leg (Heavy-leg), and light resistance knee extension training with the other leg (Light-leg).RESULTS:The MVC increased for heavy-leg (15 +/- 4%, P < 0.05), but not for light-leg (6 +/- 4%). Quadriceps CSA increased in heavy-legs (6 +/- 1%, P < 0.05) while unchanged in light-legs. Proximal PT CSA (104 +/- 4 mm(2)) was smaller than the mid-tendon CSA (118 +/- 3 mm(2)), which again was smaller than distal tendon CSA (127 +/- 2 mm(2), P < 0.05). Light-leg PT CSA increased by 7 +/- 3% (P < 0.05) at the proximal tendon level, but was otherwise unchanged. Heavy-leg PT CSA increased at the proximal and distal tendon levels by 6 +/- 3% and 4 +/- 2% respectively (P < 0.05), but was unchanged at the mid tendon level. PT stiffness increased in heavy-legs (P < 0.05) but was unchanged in light-legs. Modulus remained unchanged in both legs.CONCLUSIONS:To our knowledge, this study is the first to report tendon hypertrophy following resistance training. Further, the data show that the human PT CSA varies along the length of the tendon.