Modulation of in-vitro drug-release from a HPMC matrix system: Potential role of a disintegrant

The objective of the current study was to investigate the role of disintegrants in modulation of drug release from HPMC-based hydrophilic matrices.  The polymer matrices of a water-soluble drug, Propranolol hydrochloride, were prepared in combination with different disintegrants by wet-granulation approach. The widely used superdisintegrants like crospovidone (CP), croscarmellose sodium (CCS), calcium carboxymethyl cellulose (CaCMC) and sodium starch glycolate (SSG) were investigated for their potential role as release modifiers. The polymer-disintegrant combinations were evaluated for in-vitro drug-release behaviour at various pH conditions coupled with determination of swelling behaviour and gel properties of matrices through texture analysis. The polymer-disintegrant combinations provided control over initial release rate and also exhibited complete drug release over 24 h. The work of penetration of hydrogels after 24 h dissolution study revealed that formulation with croscarmellose sodium showed complete relaxation of gel which fostered the complete drug release. Drug-release from the developed combination matrices was observed to be primarily Fickian diffusion based, except for combination of HPMC- sodium starch glycolate based matrices, where non-Fickian behaviour was observed. Barring sodium starch glycolate, all other polymer-disintegrant combinations provided pH-independent drug release. The accelerated stability studies of optimized HPMC-disintegrant matrix system were also satisfactory.  The results of this study suggest that a suitable disintegrant when used in combination with HPMC, could modulate the drug-release and also synergize the release-controlling properties of hydrogel matrix systems. These findings can certainly be applied to develop controlled-release hydrogel matrix system of other highly water-soluble drug candidates, and hold a great potential in development of cost-effective and stable HPMC-matrix systems with customized drug-release behaviour.

Temperature Distribution during Single Pass Multi-Layer Welding in Additive Manufacturing

Single bead welding, is a high-speed welding process that is used for manufacturing of thin walled components. Its application is a vast field of research to assess its ability to manufacture complex products. This is different from the conventional welding of two similar and dissimilar materials in which the focus lies on joining of the two metals. This process is used for the creation of a completely new component by weld bead deposition of material

Effective Handover Technique in Cluster Based MANET Using Cooperative Communication

Mobile ad hoc networks (MANETs) are becoming increasingly common now a days and typical network loads considered for MANETs are increasing as applications evolve. This increases the importance of bandwidth efficiency and requirements on energy consumption delay and jitter. Coordinated channel access protocols have been shown to be well suited for MANETs under uniform load distributions. However, these protocols are not well suited for non-uniform load distributions as uncoordinated channel access protocols due to the lack of on-demand dynamic channel allocation mechanisms that exist in infrastructure based coordinated protocols. We have considered a lightweight dynamic channel allocation algorithm and a cooperative load balancing strategy that are helpful for the cluster based MANETs and an effective handover technique to improve the increased packet transmission mechanism. This helps in reduce jitter, packet delay and packet transfer speed, we use a novel handover algorithm to address this problem We present protocols that utilize these mechanisms to improve performance in terms of throughput, energy consumption and inter-packet delay variation (IPDV)

Manufacture of Functionally Gradient Materials Using Weld-Deposition

When the inherent inhomogeneity of Additive Manufacturing techniques is carefully exploited, the anisotropy transforms into the desired distribution of the properties paving the way for manufacture of Functionally Gradient Materials. The present work focuses on using welddeposition based Additive Manufacturing techniques to realize the same. Mechanical properties like hardness and tensile strength can be controlled by a smaller degree through control of process parameters like current, layer thickness etc. A wider control of material properties can be obtained with the help of tandem weld-deposition setup like twin-wire. In tandem twin-wire weld-deposition, two filler wires (electrodes) are guided separately and it is possible to control each filler wire separately. The investigations done on these two approaches are presented in pape

A Pilot Study Investigating the Impact of High Altitude on Myostatin and Irisin Levels

Many people visit and stay at high altitude due to adventure or occupation. The high-altitude environment comprises many factors alien to sea residents and detrimental to physical and mental health. Myokines are peptides and cytokines secreted from muscles and have a prime role in regulating skeletal muscle growth and myo-degradation. Therefore, the present study investigated the function of myokines in regulating muscle mass during acute and chronic high-altitude exposure. The study was conducted on Indian healthy subjects (n=29) who were distributed into three groups: Control (sea level (SL; n=15), acute high altitude stayed subjects (stayed at high altitude for less than ten days (AHA; n=7); chronic high altitude stayed subjects (stayed at high altitude for 15 days to 3 months (CHA; n=7). Acute exposure to high altitude leads to an increase in myostatin levels, indicating enhanced myo-degradation. Irisin levels were also increased in AHA group compared to SL group, depicting inclined myogenesis. However, CHA group showed an increase in myostatin levels but a non-significant change in irisin content in relation to SL group, suggesting enhanced myo-degradation. These findings generated a unique role of myokines, including myostatin and irisin, in managing skeletal muscle health with reference to high altitude.&nbsp

Green Entrepreneurs Challenges and Innovation: The Struggles They Face

Purpose:  A green entrepreneur's enterprise prioritises environmental protection by minimising the negative impact of existing products, services, or processes. It contributes to the beneficial transformation of society. This study discusses green entrepreneur challenges and innovations in Tamil Nadu's Salem District.  The intention of this study is to determine what factors determine the obstacles they experience in their business and how to transform those obstacles into opportunities   Design/methodology/approach:  Snowball sampling is employed to choose the population for this study from Salem's vast population, and the total number of respondents chosen is 50.   Findings: Simple Percentage Analysis, Chi-Square, and the Henry Garrett Ranking Method are utilised for measuring the factors. The result of testing the hypothesis indicates that there is no correlation between age and the influence to start a business using technical or professional knowledge and skill   Future Implications: Our work presents a range of theoretical and practical implications, as previously said, but it is not without limitations. In order to ascertain the direct and indirect effects of stakeholder demands, green dynamic capacity, green innovation, and firm performance, we first propose that future research make use of our framework and conduct a comparison study of small and large enterprise

Study of the dynamic interactions between vergence and accommodation

Introduction: Accommodation (change in ocular focus) and Vergence (change in ocular alignment) are two ocular motor systems that interact with each other to provide clear single binocular vision. While retinal blur drives accommodation as a reflex, retinal disparity changes accommodative position through the convergence-accommodation (or simply vergence-accommodation, VA) cross-link. Similarly, while retinal disparity primarily drives the vergence system, a change in retinal blur alters vergence through the accommodative-convergence (AC) cross-link. Although much information is known on the individual response dynamics of blur accommodation and disparity vergence, very little is known about the cross-linkages AC and VA. VA represents the unique situation where a stimulus to vergence (retinal disparity) drives a change in accommodation. When these dynamic measures are compared to those of vergence and blur accommodation a better understanding of the critical or rate limiting step within the system of vergence and accommodation can be determined. Accordingly, the purpose of this thesis was to determine the response dynamics of vergence driven accommodation (VA) and compare the response parameters to simultaneous measures of disparity vergence and blur driven accommodation. Methods: A disparity stimulus generator (DSG) was modified to allow step stimulus demands of disparity to be created on a 0. 2 cpd non-accommodative difference of Gaussian target. Retinal disparity of different step amplitude demands were created as an ON / OFF paradigm and projected on a stereo monitor set at a distance of 1. 2m. Two experiments were conducted. The first experiment investigated the first order properties of VA in comparison to similar measures of blur driven accommodation (BA). The second study aimed at comparing the first order and second order dynamics of disparity vergence, VA and BA. In the first experiment, stimulus measures of vergence, vergence-accommodation and BA were studied. Six normal young adult subjects participated in the study. Accommodation was measured continuously at 25Hz with the commercially available PowerRefractor (Multichannel systems, Germany). A Badal optical system was designed and accommodative response to step stimulus demands were measured. VA and BA measures obtained from the PowerRefractor were matched and plotted as main sequences (amplitude vs. peak velocity). Peak velocities between the two responses were compared using two-way analysis of variance (ANOVA) with Bonferroni post-tests. In the second experiment, the response dynamics of vergence, vergence-accommodation, and blur accommodation were assessed and compared on 6 young adult subjects. Eye position was measured continuously by a stereo eye tracker at a sampling rate of 120Hz. A high speed photorefractor (sampling = 60Hz) was custom designed and synchronized with a stereo eye tracker to allow simultaneous measurement of vergence and VA. Monocular blur driven accommodation measures were also obtained with the Badal optometer and the high speed photorefractor (sampling = 75Hz). VA, BA and disparity vergence responses were analyzed and temporal parameters like latency, amplitude, duration, time to peak velocity, peak acceleration, duration of acceleration, and skewness were calculated. Main sequence plots (response amplitude vs. peak velocity) were generated and compared between disparity ON and disparity OFF. The dynamic measures of VA were compared to the measures of monocular blur driven accommodation. All comparisons were done using a two-way ANOVA with Bonferroni post-tests. Results: Study 1: The results showed that response amplitude of VA during disparity ON and disparity OFF paradigms was linearly related to the peak velocity for an amplitude range of 0. 5 to 2. 5 D (Disparity ON: peak velocity of vergence-accommodation = 0. 812 * amplitude + 1. 564, R2 = 0. 452, p2 = 0. 86, p 2 = 0. 84, p2 = 0. 77, p Study 2: When amplitudes were matched, disparity vergence response during disparity ON and disparity OFF had similar main sequence relationships. The mean values for the stimulus and response VA/V ratios were similar (0. 13±0. 05 D/Δ and 0. 15±0. 09 D/Δ respectively). All the temporal parameters of vergence-accommodation were similar during disparity ON and disparity OFF paradigms. When blur accommodation and vergence-accommodation measures were compared, all the first order and second order temporal parameters in the response were similar between the two systems. Also, disparity vergence exhibited significantly greater peak velocity and peak acceleration compared to two accommodation responses. The results also confirmed that the velocity of accommodation and dis-accommodation showed a statistically significant linear relationship as a function of amplitude for the range of amplitudes tested (Accommodation, y = 2. 55x + 0. 65, R2 = 0. 55, p2=0. 65, p Conclusions: The dynamic properties of VA are amplitude dependent. Although initial results from study 1 suggested that VA may be slower during disparity ON, the results from study 2 using the high speed photorefractor and an improved analysis procedure showed that VA responses were equally fast between disparity ON (convergence) and disparity OFF (divergence). All temporal properties of VA were independent of vergence type (convergence/divergence). VA and BA have similar dynamic properties in humans suggesting that they may controlled by a common neural pathway or limited by the plant. Also, when compared to accommodation responses, disparity vergence exhibited greater velocities and accelerations reflecting the differences in the magnitude of neural innervation and plant mechanics between the two systems. The study also confirmed amplitude dependent response dynamics of blur driven accommodation and dis-accommodation

A Finite Element-Multibody Dynamics Co-simulation Methodology Applied to FAST

A co-simulation methodology is explored whereby a finite element code and a multi-body dynamics code featuring flexible cantilevered beams can be coupled and interactively executed. The floating frame of reference formulation is used to develop the equations of motion. The floating frame is fixed at the blade root. Such a formulation results in ordinary differential equations without added algebraic constraints. A variety of loose coupling and tight coupling schemes are examined for this problem. To synchronize the coupling variables, a Gauss-Seidel type iterative algorithm is used. The resulting fixed-point iterations are accelerated using Aitken’s adaptive relaxation technique. The methodology is evaluated for FAST, a wind turbine aeroelastic simulation code developed by NREL. As with FAST, many multi-body codes which can model flexibility employ modal methods. A proposed addition for FAST to simulate flexible effects using a finite element method module offers a potential to include a variety of non-linearities and also provides possibilities for using a high-fidelity aerodynamics module. The coupling schemes are compared and their applicability and limitations for different scenarios are pointed out. Results validating the approach are provided

Role of Calpeptin in Amelioration of Hypobaric Hypoxia Induced Skeletal Muscle Damage in Rats: A Pilot Study

Hypobaric hypoxia, a condition of low oxygen availability at high altitude, has a great impact on health via producing oxidative stress which could lead to protein modifications and skeletal muscle damage. Enhanced calpain activity has a major role in hypobaric hypoxia induced protein modifications and protein degradation in the skeletal muscle. The pilot study was designed to investigate the role of a calpain inhibitor, calpeptin in amelioration of hypoxia induced skeletal muscle damage. Male Sprague Dawley rats were exposed to hypobaric hypoxia (HH) with and without calpeptin (50 µg/kg, ip) treatment. HH exposure was given for 6 h at 25,000 ft. Following exposure, the animals were sacrificed and hind limb skeletal muscle was excised for analysis. Calpeptin administration inhibited protein oxidation (decrease protein carbonyl and AOPP content). Decrease in oxidized tryptophan and bityrosine content was also observed in calpeptin pre-treated group in comparison to HH exposed group. Beside this, HH induced reactive oxygen species (ROS) was also ameliorated via calpeptin treatment. Conclusively, calpeptin administration better maintained the oxidative homeostasis in skeletal muscle under hypobaric hypoxia and significantly protected against the protein damage and degradation. However, the exact mechanism is still unknown. Therefore, further research needs to be done to unravel the underlying mechanism

Fly-by-Feel Aeroservoelasticity

Recent experiments have suggested a strong correlation between local flow features on the airfoil surface such as the leading edge stagnation point (LESP), transition or the flow separation point with global integrated quantities such as aerodynamic lift. “Fly-By- Feel” refers to a physics-based sensing and control framework where local flow features are tracked in real-time to determine aerodynamic loads. This formulation offers possibilities for the development of robust, low-order flight control architectures. An essential contribution towards this objective is the theoretical development showing the direct relationship of the LESP with circulation for small-amplitude, unsteady, airfoil maneuvers. The theory is validated through numerical simulations and wind tunnel tests. With the availability of an aerodynamic observable, a low-order, energy-based control formulation is derived for aeroelastic stabilization and gust load alleviation. The sensing and control framework is implemented on the Nonlinear Aeroelastic Test Apparatus at Texas A&M University. The LESP is located using hot-film sensors distributed around the wing leading edge. Stabilization of limit cycle oscillations exhibited by a nonlinear wing section is demonstrated in the presence of gusts. Aeroelastic stabilization is also demonstrated on a flying wing configuration exhibiting body freedom flutter through numerical simulations