Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

Autonomous Adsorption Cooling—Driven by Heat Storage Collected from Solar Heat

This study investigates the performance of an adsorption chiller driven by thermal heat collected from solar collectors’ panels with heat storage. The heat is reserved in a storage tank and the reserved heat is used to drive the adsorption chiller. The investigation was carried on the climatic conditions of Dhaka, Bangladesh. Heat transfer fluid goes from the collectors to the adsorption cooling unit, then from the adsorption cooling unit to the storage tank. It is seen that heat storage is more effective than direct solar coupling; however, it requires more collectors, depending on the size of the storage tank. The analysis shows that cycle time is one of the most influential parameters for the solar-driven adsorption cooling system. It is seen that the size of the collector can be reduced if the proper cycle time is adjusted. The analysis also revealed that the system with 22 collectors (each of 2.415 m²) along with 1000 s cycle time provides better performance for the base run conditions. It is also seen that the solar-driven adsorption chiller with heat storage works well beyond the sunset time.     

Impacts of CO2 emission constraints on technology selection and energy resources for power generation in Bangladesh

This paper examines the impacts of CO₂ emission reduction target and carbon tax on future technologies selection and energy use in Bangladesh power sector during 2005–2035. The analyses are based on a long-term energy system model of Bangladesh using the MARKAL framework. The analysis shows that Bangladesh will not be able to meet the future energy demand without importing energy. However, alternative policies on CO₂ emission constraints reduce the burden of imported fuel, improve energy security and reduce environmental impacts. The results show that the introduction of the CO₂ emission reduction targets and carbon taxes directly affect the shift of technologies from high carbon content fossil-based to low carbon content fossil-based and clean renewable energy-based technologies compared to the base scenario. With the cumulative CO₂ emission reduction target of 10–20% and carbon tax of 2500 Taka/ton, the cumulative net energy imports during 2005–2035 would be reduced in the range of 39–65% and 37%, respectively, compared to the base scenario emission level. The total primary energy requirement would be reduced in the range of 4.5–22.3% in the CO₂ emission reduction targets and carbon tax 2500 Taka/ton scenarios and the primary energy supply system would be diversified compared to the base scenario.     

Design and optimization of radioisotope sources for betavoltaic batteries

A Monte Carlo source model using PENELOPE was developed to investigate different tritiated metals in order to design a better radioisotope source for betavoltaic batteries. The source model takes into account the self‐absorption of beta particles in the source which is a major factor for an efficient source design. The average beta energy, beta flux, source power output, and source efficiency were estimated for various source thicknesses. The simulated results for titanium tritide with 0° and 90° angular distributions of beta particles were validated with experimental results. The importance of the backscattering effect due to isotropic particle emission was analyzed. The results showed that the normalized average beta energy increases with the source thickness, and it reaches peak energy depending on the density and the specific activity of the source. The beta flux and power output also increase with increasing source thickness. However, the incremental increase in beta flux and power output becomes minimal for higher thicknesses, as the source efficiency decreases significantly at higher thicknesses due to the self‐absorption effect. Thus, a saturation threshold is reached. A low‐density source material such as beryllium tritide provided a higher power output with higher efficiency. A maximum power output of approximately 4 mW/cm³ was obtained for beryllium tritide with SiC. A form factor approach was used to estimate the optimum source thickness. The optimum source thickness was found near the thickness where the peak beta particle average energy occurs.     

Land surface deformation parameter estimation using persistent scatterer interferometry approach in an underground metal mining environment

Persistent scatterer interferometry (PSI) is a major advancement in radar interferometry for detecting and monitoring land deformation. PSI is the most advanced class of differential interferometric synthetic aperture radar (DInSAR) techniques. The technique conquers the main drawbacks of the conventional DInSAR technique by identifying radar targets having stable backscattering characteristics in time. These targets are termed as persistent scatterers (PSs). The higher the number of PSs for a study area the higher the accuracy of the results will be, which is most common for deformation analysis in urban areas. However, for non-urban or highly de-correlated areas, PSs density collapses significantly, which needs to increase for optimal results. For this purpose, partially coherent/distributed scatterers (DSs) are being exploited in addition to the PSs. The field surface of this study is one of the copper-rich mining belts in India, which consists of two major underground metal mines. Scatterer characterziation of the field surface under study suggests that most of the scatterers are DSs and very few scatterers under the influence of the mining zone are PSs. In addition to this, a preliminary investigation of deformation characteristics of the field surface under study reveals that the spatial extent of deformation is small/localized along with slow and non-linear deformation. Keeping in view scatterer and deformation characteristics of the field surface under study, in this research paper, a Quasi-Persistent Scatterer based PSI approach has been applied using high-resolution TerraSAR-X interferometric data stack (10 images) to generate deformation time series and deformation velocity. Furthermore, results obtained from the applied PSI approach and ground-based observations (using GNSS) have shown good agreement with each other, in the order of ?5.20?mm/year (LOS) and ?5.38?mm/year (subsiding), respectively.     

A Channel Borrowing Approach for Cluster-based Hierarchical Wireless Sensor Networks

Mobile Networks and Applications - In Wireless Sensor Networks (WSNs), energy-efficient routing is required to conserve the scarce resources of these networks. Various energy-efficient routing...     

A selective reaction of polyhydroxy fullerene with cycloaliphatic epoxy resin in designing ether connected epoxy star utilizing fullerene as a molecular core

A novel ether connected epoxy star like polymer was synthesized by selective reaction of water soluble polyhydroxy fullerene (fullerenol) with a commercial grade cycloaliphatic epoxy resin (CY-230, Ciba Geigy) in heterogeneous medium at ambient alkaline condition using tetrabutylammonium hydroxide as phase transfer catalyst. The reaction went well in such conditions and the hydroxy groups of fullerenol underwent selective nucleophilic addition reaction with polar carbonyl groups of the epoxy resin with the formation of a hemiketal. The progress of the reaction was monitored by FTIR analysis of the product formed. The disappearance of characteristic FTIR bands of fullerenol (at 1593.2, 1381.2, and 1068 cm⁻¹) and the typical carbonyl peak (at 1725 cm⁻¹) of parent epoxy resin and also changes of broad hydroxy peak (at 3431 cm⁻¹) of fullerenol into a sharp peak (at 3396.6 cm⁻¹, indicating reduced hydrophilicity) in the reaction product clearly demonstrated the chemical attachment of the epoxy units to the fullerene core. Multiple epoxy units (about 8-10) were attached to fullerene core. Non-reactivity of fullerenol towards DGEBA epoxy resin (LY 556 Ciba Geigy) in similar conditions further supports our result. The thermal properties of the product were influenced by the presence of fullerenol and exhibits higher thermal stability compared to parent epoxy. A probable reaction mechanism for the reaction has also been discussed.     

Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE₂) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.     

Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers

An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice.     

Target tracking in infrared imagery using weighted composite reference function-based decision fusion.

In this paper, we propose a novel decision fusion algorithm for target tracking in forward-looking infrared image sequences recorded from an airborne platform. An important part of this study is identifying the failure modes in this type of imagery. Our strategy is to prevent these failure modes from developing into tracking failures. The results furnished by competing ego-motion compensation and tracking algorithms are evaluated based on their similarity to a target model constructed using the weighted composite reference function.