Ejection Force Research Articles

Development and Evaluation of an Injectable Chitosan/β-Glycerophosphate Paste as a Local Antibiotic Delivery System for Trauma Care.

Complex open musculoskeletal wounds are a leading cause of morbidity worldwide, partially due to a high risk of bacterial contamination. Local delivery systems may be used as adjunctive therapies to prevent infection, but they may be nondegradable, possess inadequate wound coverage, or migrate from the wound site. To address this issue, a thermo-responsive, injectable chitosan paste was fabricated by incorporating beta-glycerophosphate. The efficacy of thermo-paste as an adjunctive infection prevention tool was evaluated in terms of cytocompatibility, degradation, antibacterial, injectability, and inflammation properties. In vitro studies demonstrated thermo-paste may be loaded with amikacin and vancomycin and release inhibitory levels for at least 3 days. Further, approximately 60% of thermo-paste was enzymatically degraded within 7 days in vitro. The viability of cells exposed to thermo-paste exceeded ISO 10993-5 standards with approximately 73% relative viability of a control chitosan sponge. The ejection force of thermo-paste, approximately 20 N, was lower than previously studied paste formulations and within relevant clinical ejection force ranges. An in vivo murine biocompatibility study demonstrated that thermo-paste induced minimal inflammation after implantation for 7 days, similar to previously developed chitosan pastes. Results from these preliminary preclinical studies indicate that thermo-paste shows promise for further development as an antibiotic delivery system for infection prevention.

Chromokinesins

During the cell cycle it is critical that the duplicated DNA faithfully segregates to give rise to two genetically identical daughter cells. An even distribution of the genome during mitosis is mediated by mitotic spindle microtubules, assisted by, among others, motor proteins of the kinesin superfamily. Chromokinesins are members of the kinesin superfamily that harbour a specific DNA-binding domain. The best characterized chromokinesins belong to the kinesin-4/Kif4 and kinesin-10/Kif22 families, respectively. Functional analysis of chromokinesins in several model systems revealed their involvement in chromosome arm orientation and oscillations. This is consistent with their originally proposed role in the generation of polar ejection forces that assist chromosome congression to the spindle equator. Kinesin-12/Kif15 members comprise a third family of chromokinesins, but their role remains less understood. Noteworthy, all chromokinesins exhibit chromosome-independent localization on spindle microtubules, and recent works have significantly extended the portfolio of mitotic processes in which chromokinesins play a role, from error correction and DNA compaction, to the regulation of spindle microtubule dynamics.

Tribological effects of mold surface coatings during ejection in micro injection molding

The effects of different mold coatings on the ejection force in micro injection molding were experimentally investigated. Two diamond-like-carbon and chromium titanium niobium nitride coatings were selected in accordance with their potential affinity with the considered injected polymers. The obtained results were correlated with the wetting properties for all the combinations of injected polymers and surface coatings. Moreover, the tribological properties of the different coatings were evaluated using an off-line friction test. The ejection force peak was correlated to the static friction coefficient. For each polymer a good linear correlation between the online and the offline friction characterization was identified, indicating the effectiveness of the proposed procedure in evaluating the tribological properties of different coatings for different polymers.

Effects of Formulation and Process Variables on Gastroretentive Floating Tablets with A High-Dose Soluble Drug and Experimental Design Approach.

To develop sustained release gastro-retentive effervescent floating tablets (EFT), a quality-based experimental design approach was utilized during the composing of a hydrophilic matrix loaded with a high amount of a highly water-soluble model drug, metformin HCl. Effects of the amount of polyethylene oxide WSR 303 (PEO), sodium bicarbonate, and tablet compression force were used as independent variables. Various times required to release the drug, tablet tensile strength, floating lag time, tablet ejection force, and tablet porosity, were selected as the responses. Polymer screening showed that PEO had the highest gel strength among the various tested polymers. Sodium bicarbonate had the most significant effect on the release rate and floating lag time by retarding the rate from the hydrophilic matrices, whilst tablet compression force and PEO exerted the greatest influence on tablet properties (p < 0.0001). The design space was built in accordance with the drug release profiles, tensile strength, and floating lag time, following failure probability analysis using Monte Carlo simulations. The kinetic modeling revealed that the release mechanism was best described by the Korsmeyer-Peppas model. Overall, the current study provided a perspective on the systematic approach of gastro-retentive EFT, loaded with highly water-soluble drugs by applying quality by design concepts.

Impact of blend properties on die filling during tableting

Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets. Additionally, the bulk residence time, ejection force, pre-compression displacement, main compression force, die fill fraction and feed frame fill fraction were determined during each run. Multivariate data analysis was applied to investigate the relation between the process parameters, blend characteristics, product and process responses. Blends with metoprolol tartrate as API showed high ejection forces. This behavior could be linked to the high wall friction value of metoprolol tartrate. The main responses related to the die filling could be predicted via a PLS model based on blend characteristics. Tablet weight variability was highly correlated with the variability on pre-compression displacement and main compression force. A good predictive model for tablet weight variability was obtained taking the porosity, wall friction angle, flowability, density, compressibility and permeability into account. Additionally, turret speed and paddle speed were included in the calibration of the model. The applied approach can save resources (material, time) during early drug product development.

Influence of Microscopic Interactions on the Flexible Mechanical Properties of Viral DNA

During the packaging and ejection of viral DNA, its mechanical properties play an essential role in viral infection. Some of these mechanical properties originate from different microscopic interactions of the encapsulated DNA in the capsid. Based on an updated mesoscopic model of the interaction potential by Parsegian et al., an alternative continuum elastic model of the free energy of the confined DNA in the capsid is developed in this work. With this model, we not only quantitatively identify the respective contributions from hydration repulsion, electrostatic repulsion, entropy and elastic bending but also predict the ionic effect of viral DNA’s mechanical properties during the packaging and ejection. The relevant predictions are quantitively or qualitatively consistent with the existing experimental results. Furthermore, the nonmonotonous or monotonous changes in the respective contributions of microscopic interactions to the ejection force and free energy at different ejection stages are revealed systematically. Among these, the nonmonotonicity in the entropic contribution implies a transition of viral DNA structure from order to disorder during the ejection.

Left atrial size and contractile function in healthy dogs and dogs with chronic mitral valve disease

ABSTRACT: In humans, left atrial enlargement and reduced contractile functions are associated with adverse cardiovascular events and a poor prognosis in many dilatation of the left atrium occurs with the gradual evolution of chronic mitral valve disease and is well diseases. The left atrium is the most compromised cardiac chamber in dogs with chronic mitral valve disease (CMVD). Therefore, this study aimed to compare the main parameters of left atrial enlargement (left atrium/aorta ratio, left atrial diameter and volume indices) and contractile function (transmitral flow peak velocity A wave and time velocity integral, atrial fraction, and atrial ejection force) at different stages of valve disease, and correlate the left atrial diameter, volume, and contractile function indices with echocardiographic variables predictive of heart failure in dogs (transmitral flow peak velocity E wave, E wave/IVRT ratio, E wave/E´wave ratio, and E wave/A wave ratio). The results showed that progressive characterized by the left atrium/aorta ratio and left atrium volume index. The left atrial diameter and volume indices and left atrium/aorta ratio correlated positively with the transmitral flow peak velocity E wave and E wave/IVRT ratio, which are important indices of diastolic function. The left atrial contractile function indices increased as CMVD evolved. Except for the atrial fraction, the left atrial contractile function indices correlated with the left ventricular filling pressure indices.

Die wall lubrication for UO2 pellets pressing: A case study

This paper investigates the tribological performance of different external lubricants on the die wall for UO2 powder pelletization without any admixed internal lubricant. Different lubricants and various ways of depositing lubricant on the die wall were investigated through different parameters during powder compaction and pellets characterization. We have thus compared depositing solid zinc stearate (StZn) lubricant by two ways (StZn powder pelletization vs. StZn spray). Results show that the tensile strength of green pellets (compacts before sintering process) is enhanced and surface defects are reduced when the lubricant is sprayed. Furthermore, the application of silicon oil on the die wall does not make it possible to manufacture UO2 pellets, which is probably due to its tribological inefficiency under pressing conditions considered in this work. By contrast, an industrial grease makes it possible to obtain green pellets with good properties and fewer surface defects. The lubrication mechanism changes from one lubricant to another and influences the pressing parameters (wall friction, friction index, ejection force, etc.) and the characteristics of the final UO2 green pellets. The ejection force seems to be more sensitive for the lubricants performance assessment in case where only external lubrication is used for nuclear powder compaction.

Evaluation of the lubricating effect of magnesium stearate and glyceryl behenate solid lipid nanoparticles in a direct compression process

The aim of this study was to develop solid lipid nanoparticles (SLN) and introduce them into a direct compression process to evaluate their lubricant properties. The study consisted of preparing glyceryl behenate SLN (Compritol® 888 ATO) by hot dispersion, and magnesium stearate SLN by a novel nanoprecipitation/ion exchange method. The ejection force was measured for nanosystems and raw materials in a formulation typically used for direct compression. The smallest particle sizes obtained were 456 nm for Compritol® 888 ATO and 330 nm for magnesium stearate. Results show that the NPs used as lubricants in a direct compression model formulation provided efficient lubrication by maintaining the lubricating properties of the system, thereby decreasing the amount of lubricant used compared to the raw material. The lubricating effect showed an increase of 15–30% for magnesium stearate and Compritol® 888 ATO, compared to the raw material at concentrations above 2%.

Chromosome Segregation Is Biased by Kinetochore Size

SummaryChromosome missegregation during mitosis or meiosis is a hallmark of cancer and the main cause of prenatal death in humans. The gain or loss of specific chromosomes is thought to be random, with cell viability being essentially determined by selection. Several established pathways including centrosome amplification, sister-chromatid cohesion defects, or a compromised spindle assembly checkpoint can lead to chromosome missegregation. However, how specific intrinsic features of the kinetochore—the critical chromosomal interface with spindle microtubules—impact chromosome segregation remains poorly understood. Here we used the unique cytological attributes of female Indian muntjac, the mammal with the lowest known chromosome number (2n = 6), to characterize and track individual chromosomes with distinct kinetochore size throughout mitosis. We show that centromere and kinetochore functional layers scale proportionally with centromere size. Measurement of intra-kinetochore distances, serial-section electron microscopy, and RNAi against key kinetochore proteins confirmed a standard structural and functional organization of the Indian muntjac kinetochores and revealed that microtubule binding capacity scales with kinetochore size. Surprisingly, we found that chromosome segregation in this species is not random. Chromosomes with larger kinetochores bi-oriented more efficiently and showed a 2-fold bias to congress to the equator in a motor-independent manner. Despite robust correction mechanisms during unperturbed mitosis, chromosomes with larger kinetochores were also strongly biased to establish erroneous merotelic attachments and missegregate during anaphase. This bias was impervious to the experimental attenuation of polar ejection forces on chromosome arms by RNAi against the chromokinesin Kif4a. Thus, kinetochore size is an important determinant of chromosome segregation fidelity.

A mechanistic study on tablet ejection force and its sensitivity to lubrication for pharmaceutical powders

Pharmaceutical powders can exhibit markedly different tablet ejection forces. The purpose of this study is to understand the factors leading to the variability of the tablet ejection force and its sensitivity to lubrication. The study showed that the tablet ejection force is mainly governed by 1) tablet diameter and thickness, 2) compact-die wall friction coefficient, and 3) residual die wall stress upon ejection; the latter was further controlled by the maximum compression pressure, as well as the degree of non-elastic deformation during compression. Brittle powders, such as lactose or dicalcium phosphate, often exhibit exceeding ejection force because of their significant contribution from the non-elastic deformation during loading. These conclusions were verified through compaction experiments of five pharmaceutical powders with diverse compaction properties. Additionally, we found that boundary lubrication was highly effective in reducing tablet ejection force, achievable through decreasing the compact-die wall friction coefficient, but not through altering the intrinsic consolidation behavior of powders. High ejection force is indicative of the sub-optimal stress condition of the tablet post-unloading. Therefore learnings from this study are beneficial for practitioners to harness the ejection force as an effective metric to identify and mitigate risks of tablet defects.

The importance of the amount/thickness of die wall lubricant for UO2 pellets pressing

External lubrication is often used to complete compaction process of powder materials. The main goal of this method is generally to reduce the amount of admixed internal lubricant (Zinc stearate powder) within the raw material. The application of external lubricants enhances the density uniformity and the mechanical strength of the resulting compacts. This study investigates the effects of the external lubricant amount for UO2 powder compaction and the properties of the corresponding green pellets (corresponding to the compacts before sintering) without any admixed lubricant in the raw powder in order to evaluate the feasibility of this route in the case of nuclear powder. Results show that there is a quantity or number of layers from which the external lubricant applied on the die wall becomes detrimental to the friction index and the ejection force measured during the pressing cycle. The quality (surface defects, mechanical strength) of the green pellets can also be affected by the amount of lubricant. Thus the quantity and the thickness of the die wall lubricant must be optimized in order to assure an efficient mixed lubrication mode corresponding to the better lubrication mode in our study case.

Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR.

The transcription repressor BACH1 performs mutually independent dual roles in transcription regulation and chromosome alignment during mitosis by supporting polar ejection force of mitotic spindle. We now found that the mitotic spindles became oblique relative to the adhesion surface following endogenous BACH1 depletion in HeLa cells. This spindle orientation rearrangement was rescued by re-expression of BACH1 depending on its interactions with HMMR and CRM1, both of which are required for the positioning of mitotic spindle, but independently of its DNA-binding activity. A mass spectrometry analysis of BACH1 complexes in interphase and M phase revealed that BACH1 lost during mitosis interactions with proteins involved in chromatin and gene expression but retained interactions with HMMR and its known partners including CHICA. By analyzing BACH1 modification using stable isotope labeling with amino acids in cell culture, mitosis-specific phosphorylations of BACH1 were observed, and mutations of these residues abolished the activity of BACH1 to restore mitotic spindle orientation in knockdown cells and to interact with HMMR. Detailed histological analysis of Bach1-deficient mice revealed lengthening of the epithelial fold structures of the intestine. These observations suggest that BACH1 performs stabilization of mitotic spindle orientation together with HMMR and CRM1 in mitosis, and that the cell cycle-specific phosphorylation switches the transcriptional and mitotic functions of BACH1.

EFFECTS OF LAUNCHING PARAMETERS ON THE SEPARATION TRAJECTORY OF INTERNAL WEAPONS

A simplified buried weapon bay-door-missile model was simulated with Improved Delayed Detach Eddy Simulation (IDDES) method and dynamic grid technique under the condition of different inflow Mach numbers, launching speeds and initial angular velocities. The separation trajectory varying patterns of different cases were obtained. The results show that, in subsonic flow, the Mach number has little effect on the yaw angle, while under transonic and supersonic conditions, the missile yaws to the right due to the influence of shock waves. The increase in the Mach number leads to the reduction of missile yaw and pitch angle for supersonic inflow. Raising the launching speed can make the store reach safe separation distance faster and diminish store angular variation. Increasing the initial angular velocity of the missile can reduce the pitch angle and increase the separation speed of the missile without changing the ejection force.

Effect of ultrasound vibration on the ejection friction in microinjection molding

The form accuracy of microinjection-molded parts is significantly affected by the friction at the interface with the mold during the ejection phase. In this work, an ultrasound-assisted ejection system was designed and tested for different polymers (PS, COC, and POM) and mold topographies. The proposed innovative solution aims at reducing the ejection friction by decreasing the adhesion component of the frictional force, which is controlled by the real contact area generated during the filling phase of the injection molding process. The experiments indicate a positive effect of ultrasound vibration on the friction force values acquired during ejection, with a maximum reduction of 16% for PS. The effect depends on polymer selection and it increases for higher mold roughness. Moreover, the combined effect on the ejection force of mold surface roughness, melt viscosity during filling and polymer elastic modulus at ejection was modeled to the experimental data. This demonstrated that the effect of ultrasound vibration on the ejection friction reduction is due to the heating of the contact interface and the consequent reduction of the polymer elastic modulus.

Increasing the Injection Moulding Productivity through EDM Surface Modulation

The productivity of the injection moulding process is considerably deteriorated due to the demoulding issues as a result of increasing part and polymer complexity. An effective method to overcome some of the issues is the application of coatings on mould surface to reduce adhesion and friction during the moulded part ejection. In such solutions, the mould is coated after the machining by methods such as milling and EDM. In fact, die-sinking EDM is widely used to machine moulds with high accuracy, surface quality and aspect ratios. In this research, a novel method is analysed where the texture of the EDM surface is modulated to achieve desirable surface functionality, leading to reduction of part sticking during ejection in injection moulding. The effect of primary parameters of EDM process on the resulting surface is analysed. It is seen that while the surface amplitude parameters such as Ra and Rz remain similar to the standard eroded surface, the spacing parameter RSm and slope measure RΔq can be modulated. The effect of the surface texture during injection moulding is evaluated by measuring the forces during the ejection stage to characterise part sticking. Similar or considerably reduced ejection forces are observed for the modulated EDM texture compared to the polished surfaces, depending on the polymer type and part geometry. The ejection force observations are correlated to the static and dynamic friction coefficient of surface textures against different polymers. The reduction of ejection forces comparable to the coated surfaces places surface texturing as an effective alternative or a supplement to reduce the demoulding issues and thus increasing the injection moulding productivity and part quality.

Surface Integrity Evaluation of Modified EDM Surface Structure

Surface engineering, through either texturing or surface modification, for enhanced functionality is currently one of the most emerging research topic/technologies. This is mainly related to its huge commercial potential in terms of added value or product customisation, with applications extending from tooling, to mould & die, medical, food & drink, aerospace and others. With the recent advances in EDM generator design and process control, a number of commercial solutions were released by leading technology providers where it is deemed possible to apply a certain surface finish/structure, resulting in enhanced functionality (e.g. reduced friction or reduced/controlled adhesion) via the EDM process itself and without the need for a secondary operation. This paper investigates the surface integrity effects for this modified surface structuring concept (3DS). Experimental results showed that it was possible to reduce the friction coefficient (consequently ejection forces in the injection moulding process, for example) by as much as 60%, compared to samples machined using standard EDM settings while both having similar Ra values. 3DS samples however showed slightly lower fatigue performance which is likely to be the result of surface micro-cracking which appeared to be more prominent on these, compared to the standard EDM samples.

Change of “Left atrium ejection force” after transcatheter “Atrial septal defect” closure using “AMPLATZER,” in pediatric patients

Background and Purpose: There has not been any study regarding atrial systolic function in transcatheter atrial septal defect (ASD) closure. The aim of this study was to survey left atrium ejection force in this procedure in the pediatric age group. Subjects and Methods: This was an observational (before and after) study. Pediatric patients who underwent transcatheter ASD closure using “AMPLATZER” at “Rajaei Cardiovascular Medical and Research Center,” from March to December 2013, were enrolled consecutively. Physical examination and transthoracic echocardiography were performed for the patients before and 12–24 h after the procedure, and left atrium ejection force was calculated. Results: Totally, 63 patients (age: 6.11 ± 3.43 [1–14] years and weight: 21.53 ± 10.79 [9.7–48] kg) were studied. ASD size was 11.43 ± 3.30 (5–22) mm. Left atrium ejection force, before and after the procedure, was 7.19 ± 6.06 (0.33–32.54) kilodyne and 6.30 ± 4.03 (0.5–18.16) kilodyne, respectively (P = 0.28). There was no significant difference between pre- and postprocedure left atrium ejection force in different age group, both genders, types of the device, and ASD size. Postprocedure left atrium ejection force was significantly lower in the patients with large devices (diameter of left atrial disk to body surface area ratio index >40 mm/m2) than smaller device. Conclusion: This study showed that left atrium ejection force after transcatheter ASD closure does not change significantly at early stage, so atrial systolic function is maintained in the presence of the device. In the patients with large device, left atrium ejection force may decrease.

Prevention of seizure in ejection of compact by control of internal diameter of container

To decrease the ejection force and to prevent the seizure during ejection in compaction of iron powder without lubricant, a compaction process using control of an internal diameter of a die using a shrinkage ring is developed. The internal diameter before the compaction is decreased by inserting the container into the shrinkage ring, and the internal diameter after the compaction is increased by releasing the shrinkage ring from the die. The friction during the ejection of the compact is decreased by the difference in elastic recovery between the die and compact.

Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets

The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental design was used to generate a structured study plan which involved 19 runs. The formulation variables studied were the type of lubricant (magnesium stearate or stearic acid) and its concentration (0.5, 1.0 and 1.5%). Process variables were total production feed rate (5, 10.5 and 16kg/h), mixer speed rpm (500, 850 and 1200rpm), and mixer inlet port for lubricant (A or B). The continuous direct compression tableting line consisted of loss-in-weight feeders, a continuous mixer and a tablet press. The Quality Target Product Profile (QTPP) was defined for the final product, as the flowability of powder blends (2.5s), tablet strength (147N), dissolution in 2.5min (90%) and ejection force (425N). A design space was identified which fulfilled all the requirements of QTPP. The type and concentration of lubricant exerted the greatest influence on the design space. For example, stearic acid increased the tablet strength. Interestingly, the studied process parameters had only a very minor effect on the quality of the final product and the design space. It is concluded that the continuous direct compression tableting process itself is insensitive and can cope with changes in lubrication, whereas formulation parameters exert a major influence on the end product quality.