Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain ...limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer–Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome® for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.
This paper reports the enhanced performance of cholesterol oxidase (COx) conjugated CdSe/ZnS quantum dots (QDs) by using water-soluble mercaptoacitic acid (MAA) as linker. The functionalized ...MAA-CdSe/ZnS QDs conjugated in four different dilutions of cholesterol oxidase significantly affected QDs photoluminescence intensities, which affected the process of charge transfer from QDs to MAA. The conjugation of COx to MAA-QDs in increased dilutions resulted in the regain of PL intensities, which were attributed to the passivation of MAA HOMO/LUMO states. The electrochemical impedance spectroscopy and cyclic voltammetry of the conjugated QDs were performed to get study the charge transfer mechanism. The 1:1000 diluted COx conjugated MAA-CdSe/ZnS QDs was found to have the lowest charge transfer resistance of 228 Ω, the highest diffusion (~ 1.39 × 10
cm
/s) and charge transfer rates (~ 4.5 × 10
s
) between the electrode and the redox species. The current study demonstrated the sensitivity of electrochemical and optical based detection on the alkaline.
The highly efficient Interior Permanent Magnet Synchronous Motor (IPMSM) is ubiquitous choice in Electric Vehicles (EVs) for today’s automotive industry. IPMSM control requires accurate knowledge of ...an immeasurable critical Permanent Magnet (PM) flux linkage parameter. The PM flux linkage is highly influenced by operating temperature which results in torque derating and hence power loss, unable to meet road loads and reduced life span of electrified powertrain in EVs. In this paper, novel virtual sensing scheme for estimating PM flux linkage through measured stator currents is designed for an IPMSM centric electrified powertrain. The proposed design is based on a Uniform Robust Exact Differentiator (URED) centric Super Twisting Algorithm (STA), which ensures robustness and finite-time convergence of the time derivative of the quadrature axis stator current of IPMSM. Moreover, URED is able to eliminate chattering without sacrificing robustness and precision. The proposed design detects variation in PM flux linkage due to change in operating temperature and hence is also able to establish characteristics of fault detection. The effectiveness and accuracy in different operating environments of the proposed scheme for nonlinear mathematical IPMSM model with complex EV dynamics are verified thorough extensive simulation experiments using MATLAB/Simulink.
Power Domain Non-Orthogonal Multiple Access (PD-NOMA) is a potential technology for the next generation of cellular networks. Compared to classical orthogonal multiple access (OMA) techniques, ...PD-NOMA leverages the distinct channel gains of users for multiplexing different signals in a single resource block (time, frequency, code) in power domain. This results in higher spectral efficiency, improved user fairness, better cell-edge throughput, increased reliability and connectivity and low-latency. The flexible combination of PD-NOMA with existing and emerging technologies such as heterogeneous networks (HetNets), multiple-input multiple-output (MIMO), massive MIMO, cooperative communication, cognitive radios (CRs), millimeter wave communication, simultaneous wireless information and power transfer (SWIPT), visible light communication (VLC), mobile edge computing (MEC), intelligent reflecting surfaces (IRS), unmanned aerial vehicles (UAVs), underwater communication etc., is expected to cause further enhancements in performance. Existing survey papers on NOMA mainly focus on its concept, comparison, issues and analysis without any categorization of different techniques to solve the issues related to it. This survey paper highlights the main issues and constraints of resource allocation, signaling, practical implementation and security aspects of NOMA and its integration with 5G and upcoming wireless technologies. Various solutions have been proposed in the literature that involve optimization, analytical, game theory, matching theory, graph theory and machine learning (ML) techniques. We present an in-depth analysis and comparison of these solutions with key insights emphasizing the feasibility and applicability for a qualitative analysis. We finally identify promising future research directions and challenges in the context of PD-NOMA’s application to the existing 5G and next generation wireless networks.
The biogeochemical formation of dimethyl sulfide (DMS) from the Southern Ocean is complex, dynamic, and driven by physical, chemical, and biological processes. Such processes, produced by marine ...biogenic activity, are the dominant source of sulfate aerosol over the Southern Ocean. Using an atmosphere-only configuration of the United Kingdom Earth System Model (UKESM1-AMIP), we performed eight 10-year simulations for the recent past (2009–2018) during austral summer. We tested the sensitivity of atmospheric DMS to four oceanic DMS datasets and three DMS transfer velocity parameterizations. One oceanic DMS dataset was developed here from satellite chlorophyll a. We find that the choice of oceanic DMS dataset has a larger influence on atmospheric DMS than the choice of DMS transfer velocity. Simulations with linear transfer velocity parameterizations show a more accurate representation of atmospheric DMS concentration than those using quadratic relationships. This work highlights that the oceanic DMS and DMS transfer velocity parameterizations currently used in climate models are poorly constrained for the Southern Ocean region. Simulations using oceanic DMS derived from satellite chlorophyll a data, and when combined with a recently developed linear transfer velocity parameterization for DMS, show better spatial variability than the UKESM1 configuration. We also demonstrate that capturing large-scale spatial variability can be more important than large-scale interannual variability. We recommend that models use a DMS transfer velocity parameterization that was developed specifically for DMS and improvements to oceanic DMS spatial variability. Such improvements may provide a more accurate process-based representation of oceanic and atmospheric DMS, and therefore sulfate aerosol, in the Southern Ocean region.
Objective
To understand why skilled birth attendance—an acknowledged strategy for reducing maternal deaths—has been effective in some settings but is failing in Pakistan and to demonstrate the value ...of a theory‐driven approach to evaluating implementation of maternal healthcare interventions.
Design
Implementation research was conducted using an institutional ethnographic approach.
Setting and population
National programme and local community levels in Pakistan.
Methods
Observations, focus group discussions, and in‐depth interviews were conducted with 38 Community Midwives (CMWs), 20 policymakers, 45 healthcare providers and 136 community members. A critical policy document review was conducted. National and local level data were brought together.
Main outcomes
Alignment of programme theory with real‐world practice.
Results
Data revealed gaps between programme theory, assumptions and reality on the ground. The design of the programme failed to take into account: (1) the incongruity between the role of a midwife and dominant class and gendered norms that devalue such a role; (2) market and consumer behaviour that prevented CMWs from establishing private practices; (3) the complexity of public–private sector cooperation. Uniform deployment policies failed to consider existing provider density and geography.
Conclusions
Greater attention to programme theory and the ‘real‐world’ setting during design of maternal health strategies is needed to achieve consistent results in different contexts.
Similar to other developing countries, Pakistan is going through a rapid nutrition transition where shift from underweight to overweight and obesity is occurring. In this paper, we report on the ...relationship of household socioeconomic position (SEP), community SEP and urbanicity with under- and over-weight categories of BMI among Pakistani women.
We analyzed data on 4,767 women ages 15-49 years enrolled in a nationally representative Pakistan Demographic Health Survey (PDHS) conducted in 2012-13 that employed a multistage, stratified cluster sampling design. We assessed the association of urbanicity, household and community SEP derived from household assets and utilities, with categories of body mass index (BMI) using multinomial regression analysis where normal weight (BMI 18.6-22.5) was the reference category.
Thirteen percent of women were underweight (BMI <18.5), 15% pre-overweight (BMI: 22.6-24.9), 25% overweight (BMI: 25.0-29.9) and 14% were obese (BMI≥30). Pre-overweight, overweight and obesity among women increased across household wealth quintiles (HWQs) in a graded fashion whereas there was no significant difference in underweight by household wealth. Women in urban areas were more likely to be obese. There was a pronounced increase in adjusted odds ratios (aORs) for overweight/obesity across HWQs within urban areas compared to rural areas. There was a steeper gradient in aORs for obesity from 1st to 5th HWQs in high income communities compared to the middle- and low income communities. In community-level analyses, communities in urban areas were more likely to have higher levels of obesity while in rural areas, especially in Sindh, more communities were more likely to have a higher level of underweight.
A shift to higher overweight and obesity than underweight in Pakistan is associated with high household and community wealth as well as living in urban areas. Clustering of obesity and underweight in distinct communities afford opportunity for tailored intervention programs.
Transition metal dichalcogenides (TMDs) are promising materials for photocatalytic functions. In class of TMDs, MoS2 is comprehensively explored as a co-catalyst due to the extraordinary activity for ...photocatalytic activity of organic dye degradation. But the catalytic activities of MoS2 are generated through S ions on depiction edges. Also numerous of S ions existed on basal planes are catalytically inactive. The insertion of external metals in MoS2 organism is extensive way for activation of basal planes surface to enhance concentration of catalytically active sites. For this purpose, nanoparticles of Nickel (Ni) doped MoS2 are prepared by hydrothermal technique. Structural and morphological analysis are characterized by XRD and SEM, respectively. XRD results showed that Ni is completely doped into MoS2. SEM showed that pure MoS2 has sheet like structure and Ni doped MoS2 has mix disc and flower like structure. Band gap energy was observed in declining range of 2.30-1.76 eV. The photocatalytic activity of pure MoS2 and Ni doped MoS2 were evaluated by degrading MB and RhB dyes under UV light irradiation. MB dye degradation of MB was 71% for pure MoS2. For 1% to 5% Ni doping in MoS2, MB dye degradated from 85% to 96%. It means that MB dye degradation of MB was enhanced continuously by increasing the concentration of Ni doping. RhB dye degradation of RhB was 62% for pure MoS2. For 1% to 5% Ni doping in MoS2, the RhB dye degradated from 77% to 91%.
We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to ...adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model.
The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue.
We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The claimed dosage strategy achieves the p53 response in the first case. However, for the induction of oscillations, it is shown through bifurcation analysis that to achieve oscillating behavior of p53 inhibition of Mdm2 is not enough, rather antirepression of the p53-Mdm2 complex is also needed which leads to the need of a new drug design paradigm.
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•We investigated the cellular mechanism of action of drug nutlin.•integrated model of (Hunziker (2010) and Puszynski (2014)) to repress the p53-Mdm2.•To perceive the drug dosage design for Nutlin to revive the function of the p53
Buffalo is one of the leading milk-producing dairy animals. Its production and reproduction are affected due to some factors including inadequate monitoring around parturition, which cause economic ...losses like delayed birth process, increased risk of stillbirth, etc. The appropriate calving monitoring is essential for dairy herd management. Therefore, we designed a study its aim was, to predict the calving based on automated machine measured prepartum behaviors in buffaloes. The data were collected from n=40 pregnant buffaloes of 2nd to 5th parity, which was synchronized. The NEDAP neck and leg logger tag was attached to each buffalo at 30 days before calving and automatically collected feeding, rumination, lying, standing, no. of steps, no. of switches from standing to lying (lying bouts) and total motion activity. All behavioral data were reduced to -10 days before the calving date for statistical analysis to use mixed model procedure and ANOVA. Results showed that feeding and rumination time significantly (P<0.05) decreased from -10 to -1 days before calving indicating calving prediction. Moreover, Rumination time was at lowest (P<0.001) value at 2h before the calving such behavioral changes may be useful to predict calving in buffaloes. Similarly, lying bouts and standing time abruptly decreased (P<0.05) from -3 to -1 days before calving, while lying time abruptly increased (P<0.01) from -3 to -1 days before calving (531.57±23.65 to 665.62±18.14, respectively). No. of steps taken and total motion significantly (P<0.05) increased from -10 to -1 days before calving. Feeding time was significantly (P<0.02) lowered in 3rd parity buffaloes compared with 2nd, 4th and 5th parity buffaloes, while standing time of 5th parity buffaloes were lowered (P<0.05) as compared to 2nd to 4th parity buffalos at -1 day of prepartum. However, rumination, lying, no. of steps taken and total motion activity at -1 day of prepartum was independent (P>0.05) of parity in buffaloes. Neural network analysis for combined variables from NEDAP technology at the daily level yielded 100.0% sensitivity and 98% specificity. In conclusion NEDAP technology can be used to measured behavioral changes -10 day before calving as it can serve as a useful guide in the prediction calving date in the buffaloes.
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