Parasitic Resistance Research Articles

Proposition of In silico Pharmacophore Models for Malaria: A Review.

In the field of medicinal chemistry, the concept of pharmacophore refers to the specific region of a molecule that possesses essential structural and chemical characteristics for binding to a receptor and eliciting biological activity. Understanding the pharmacophore is crucial for drug research and development, as it allows the design of new drugs. Malaria, a widespread disease, is commonly treated with chloroquine and artemisinin, but the emergence of parasite resistance limits their effectiveness. This study aims to explore computer simulations to discover a specific pharmacophore for Malaria, providing new alternatives for its treatment. A literature review was conducted, encompassing articles proposing a pharmacophore for Malaria, gathered from the "Web of Science" database, with a focus on recent publications to ensure up-to-date analysis. The selected articles employed diverse methods, including ligand-based and structurebased approaches, integrating molecular structure and biological activity data to yield comprehensive analyses. Affinity evaluation between the proposed pharmacophore and the target receptor involved calculating free energy to quantify their interaction. Multiple linear regression was commonly utilized, though it is sensitive to multicollinearity issues. Another recurrent methodology was the use of the Schrödinger package, employing tools such as the Phase module and the OPLS force field for interaction analysis. Pharmacophore model proposition allows threedimensional representations guiding the synthesis and design of new biologically active compounds, offering a promising avenue for discovering therapeutic agents to combat Malaria.

β-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that β-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance between susceptible Plasmodium falciparum and four different drug-resistant strains. In this report, we describe the synthesis and in vitro antimalarial evaluation of 91 new derivatives of 1a. The asexual blood stage growth inhibition data show a clear preference for a 3,4-dihalogenated, 3,5-dihalogenated, 3,4,5-trichloro-, or 4-trifluoromethyphenyl ring at the C1-position. The most potent compound, 3,4,5-trichlorophenyl-substituted 42a, is twice as potent as 1a. Six potent analogues were assessed for their drug-like properties, and four of these were subjected to in vitro barcoded cross-resistance profiling. Compounds 1a, 1m, 42a, and 42m showed no cross-resistance to 32 resistance mutations on the Dd2 genetic background and 10 resistance mutations on the 3D7 genetic background. These data suggest that compounds in this scaffold possess a novel mechanism of antimalarial action.

Adding gastrointestinal parasite resistance to the breeding objective in hair sheep: initial steps.

The U.S. Maternal Hair index was designed by the National Sheep Improvement Program (NSIP) to increase total weight of lamb weaned per ewe lambing (TW). Producers are interested in adding gastrointestinal nematode (GIN) resistance to this breeding objective since parasitism causes substantial economic losses. The NSIP provides producers with estimated breeding values (EBV) for post-weaning fecal egg count (PFEC), an indicator of GIN resistance. Our objective was to gauge the effects of including PFEC as another selection criterion and goal trait. Selection index theory was used to construct 11 indexes. First was a benchmark index with TW as the goal. Weaning weight, and number of lambs born and weaned, were selection criteria. An index was then designed with PFEC added as a selection criterion. In 9 more indices, PFEC was also included as a goal trait, where the economic value of TW was scaled relative to that of PFEC. PFEC received a scaled economic value of -1 with that of TW increasing from +1 to +5 at +0.5 increments. Selection criteria were modelled as EBV or phenotypes. Annual genetic responses in goal traits were predicted. The top 3% of males and 26% of females were selected. Breeding values and phenotypes were simulated for 200 lambs by Cholesky decomposition and used to generate index scores, with 100 replicates run. Concordances with the animals selected in the benchmark scenario were determined. Using EBV as selection criteria, TW increased by 1.46kg/yr in the benchmark scenario. However, unfavorably, PFEC increased by 2.24%/yr. When using phenotypic criteria, TW increased by 0.52kg/yr and PFEC by 0.28%/yr. Once added as a goal trait, PFEC decreased regardless of the scaled economic value of TW. However, responses in TW were also reduced, although less so as its scaled economic value increased. A scaled economic value of +3 for TW appeared reasonable over other choices with 79% of the emphasis placed on TW in the breeding objective. With EBV as selection criteria, PFEC declined by 7.96%/yr with 98% of the response in TW retained. Also, on average, 64% of males and 80% of females were chosen in common with the benchmark. With phenotypic selection criteria, PFEC declined by 5.13%/yr and 94% of the response in TW was retained; 61% of males and 80% of females were chosen in common with the benchmark. Implementing an index with scaled economic values of +3 for TW and -1 for PFEC would balance gains in TW with reductions in PFEC.

Molecular docking, network pharmacology, and QSAR modelling studies of benzo[c]phenanthridines - novel antileishmaniasis agents.

Leishmaniasis treatment primarily relies on chemotherapy due to lack of vaccines. However, the low efficacy, parasite resistance, and toxicity associated with existing drugs necessitate the development of effective and safer therapies. Fuchino etal. reported promising leishmanicidal activity in a series of benzo[c]phenanthridines against L. major promastigotes. To progress these compounds towards drug development, it is crucial to understand their molecular targets, mechanisms of action, binding interactions, and structural requirements. In this research, molecular docking, network pharmacology, 2D-QSAR, and 3D-QSAR CoMFA studies were performed on 30 benzo[c]phenanthridines. Docking analysis showed that all molecules had a strong binding affinity to L. major-nucleoside diphosphate kinase (NDPK) compared to the other targets. 10-isopropoxy sanguinarine had the highest binding affinity (-10.6 kcal/mol) and formed ionic and hydrophobic interactions. Network pharmacology analysis of the most active compounds identified serine/threonine-protein kinase Mtor as a potential antileishmaniasis target in humans for benzo[c]phenanthridines. This was confirmed with high-affinity scores > -7.0 kcal/mol for all the compounds docked. GO and KEGG pathway enrichment identified Reg. of fatty acid oxidation (BP), TORC1 complex (CC), RNA polymerase III type 1 promoter sequence-specific DNA binding (MF), and Acute myeloid leukemia (KEGG pathway) to be highly enriched with the hub genes. Both 2D and 3D-QSAR CoMFA models satisfied the internal and external validation tests as follows: 2D-QSAR: R2Train = 0.9040, Q2cv = 0.8648, R2adj = 0.8838, and R2Test = 0.8740; and 3D-QSAR: r2 = 0.998, q2 = 0.526, and SDEP = 0.856. The molecules can be practically evaluated as superior antileishmaniasis agents.

Exposure to fungal infection decreases eye size in the zooplankton, Daphnia

Abstract Immune responses can be energetically expensive and subject to trade-offs. Prior work on the freshwater zooplankton, Ceriodaphnia cornuta, demonstrated an association between eye size and infection, leading to questions about whether investment in eyes trades off against investment in immunity. We used the crustacean host, Daphnia dentifera, and its fungal parasite, Metschnikowia bicuspidata, to investigate the relationships between eye size, parasite resistance and infection. In the field, we found a negative correlation between size-corrected eye area (SCEA) and Metschnikowia infection, suggesting that either SCEA decreases infection (thereby indicating resistance) or that infection decreases SCEA. Controlled laboratory experiments reinforced the latter result: exposure to the fungal parasite decreased a host’s SCEA, regardless of the parasite dose or host genotype. We also uncovered significant plasticity in this trait—both host age and resource level increased SCEA. Identifying causality in physiological correlations is challenging. Our results suggest that negative associations between parasitism and energetically-expensive traits can arise through plasticity.

Presence of Plasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya

Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.

Modeling and characterization of low frequency noise in self-aligned top-gate coplanar IGZO thin-film transistors

Abstract A modified low-frequency noise (LFN) model was proposed to accurately estimate the quality of the gate dielectric in self-aligned top-gate (SA TG) coplanar structure indium–gallium–zinc oxide (IGZO) thin-film transistors (TFTs). The proposed LFN model was derived by modifying the conventional carrier number with correlated mobility fluctuation model considering the peculiar characteristics of SA TG coplanar IGZO TFTs such as the channel length reduction due to the diffusion of hydrogen atoms or oxygen vacancies from the source/drain to the channel, as well as the relatively large source/drain parasitic resistance. The proposed model was validated by demonstrating that the measured LFN values were in good agreement with the predicted values from the proposed model for all SA TG coplanar IGZO TFTs with SiO2 gate dielectrics deposited under different plasma-enhanced chemical vapor deposition (PECVD) power densities. The near-interface gate dielectric trap densities extracted from each TFT using the proposed LFN model revealed a clear increase as the PECVD power increased, which is considered a major cause of poor positive-bias-temperature-stress stability of the SA TG coplanar IGZO TFT with SiO2 gate dielectric deposited under high PECVD power conditions.

Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b

Drug resistance against antimalarials is rendering them increasingly ineffective and so there is a need for the development of new antimalarials. To discover new antimalarial chemotypes a phenotypic screen of the Janssen Jumpstarter library against the P. falciparum asexual stage was undertaken, uncovering the cyclopropyl carboxamide structural hit class. Structure-activity analysis revealed that each structural moiety was largely resistant to change, although small changes led to the frontrunner compound, WJM280, which has potent asexual stage activity (EC50 40 nM) and no human cell cytotoxicity. Forward genetics uncovered that cyclopropyl carboxamide resistant parasites have mutations and an amplification in the cytochrome b gene. Cytochrome b was then verified as the target with profiling against cytochrome b drug-resistant parasites and a mitochondrial oxygen consumption assay. Accordingly, the cyclopropyl carboxamide class was shown to have slow-acting asexual stage activity and activity against male gametes and exoerythrocytic forms. Enhancing metabolic stability to attain efficacy in malaria mouse models remains a challenge in the future development of this antimalarial chemotype.

Host genetic diversity and body condition influence parasite resistance and clearance in a wild marine mammal population.

Host genetic variability can modulate infection resistance, although its role in infection clearance remains unclear. Hookworm disease (Uncinaria sp.) is the leading cause of pup mortality in several otariid species, although the parasite can be cleared through immune-mediated processes. We evaluated the association of host genetic diversity, body condition and immune response with hookworm resistance and/or clearance in the South American fur seal (Arctocephalus australis). Uninfected pups had higher heterozygosity than parasitized individuals, indicating a negative relationship between heterozygosity and the chances of infection. Likewise, pups that died of hookworm infection had lower heterozygosity than those that died of non-infectious causes. Interestingly, once infected, pups that survived hookworm infection had heterozygosities similar to pups that died of hookworm disease. However, pups that cleared the infection had a higher body mass and parasite-specific immunoglobulin G levels than those that did not recover or died of hookworm disease. Thus, although heterozygosity predicted resistance to and mortality from hookworm infections, it did not affect parasite clearance, which was facilitated by better body condition and adaptive immune responses. This demonstrates that host genetic variability and host-environment interactions influence disease dynamics, acting at different, well-defined stages of infection.

A Novel Method to Extract Channel Mobility and Parasitic Resistance of 2-D Material MOSFETs

A Novel Method to Extract Channel Mobility and Parasitic Resistance of 2-D Material MOSFETs

<i>In-Silico</i> Screening of Prenylated Quercetin from <i>Globimetula oreophila</i> Against <i>Plasmodium falciparum</i> Enzymes: Hope for New Antimalarial Drugs

Malaria continues to be one of the most devastating global health problems due to the high morbidity and mortality it causes in endemic regions. The search for new antimalarial targets is vital because of the increasing prevalence of drug resistance in malaria parasites. Malarial proteases constitute promising therapeutic targets as they play important roles in the parasite life cycle. The inhibition of these enzymes has pharmacological and therapeutic significance since they are involved in numerous processes, including the development, invasion, egress, and breakdown of host hemoglobin to release amino acids for parasite sustenance. In this study, <i>in silico</i> techniques were used to shed light on the mechanisms underlying the inhibitory effects of prenylated quercetin isolated from <i>Globimetula oreophila</i> on plasmepsin I and II, falciparum 2 and 3, <i>Plasmodium falciparum</i> calcium-dependent protein kinase 2, dihydrofolate reductase-thymidylate synthase, and serine repeat antigen 5. The test compound significantly interacts with key enzyme binding pockets through hydrogen bonds, van der Waals, and hydrophobic interactions, influencing protease specificity control. Crucial ligand features like carbonyl and hydroxyl groups were identified as essential for receptor interactions. Comparative analysis revealed the test compound's strong binding affinities with energies ranging from -6.4 Kcal/mol to -9.4 Kcal/mol, indicating competitive potential against various enzymes, particularly excelling against <i>Pf</i>DHFR-TS, plasmepsin-I, and SERA5 compared to native ligands. This suggests the compound's ability to competitively inhibit enzyme activity by targeting co-factor binding sites, especially with specific proteases, holding promise for therapeutic applications as potent inhibitors for the prevention and treatment of malaria.

Investigation of Novel Isatinylhydantoin Derivatives as Potential Anti-kinetoplastid Agents.

Neglected tropical diseases are a group of infectious diseases with a high endemicity in developing countries of Africa, Asia, and the Americas. Treatment for these diseases depends solely on chemotherapy, which is associated with severe side effects, toxicity, and the development of parasitic resistance. This highlights a critical need to develop new and effective drugs to curb these diseases. As a result, a series of novel isatinylhydantoin derivatives were synthesized and evaluated for in vitro anti-kinetoplastid activity against seven human- or animal-infective Trypanosoma and two human-infective Leishmania species. The synthesized derivatives were tested for potential cytotoxicity against human, animal, and parasite host-related cell lines. The isatinylhydantoin hybrid 4b bearing 5-chloroisatin and p-bromobenzyl moieties, showed strong trypanocidal activity against blood-stage T. congolense parasites; however, the promising in vitro trypanocidal potency of 4b could not be translated to in vivo treatment efficacy in a preliminary animal study. Compounds 5, 2b, and 5b, were the most active against amastigotes of L. donovani, showing higher leishmanicidal activity than the reference drug, amphotericin B. These compounds were identified as early antileishmanicidal leads, and future investigations will focus on confirming their antileishmanial potential through in vivo efficacy evaluation as well as their exact mechanism of action.

Comprehensive evaluation of recombination confined performance of CuGaO2 for solar cell application

In the quest to find an outstanding solar energy capturing system that meets requirements like affordability, widespread availability, eco-friendliness, remarkable efficiency, and enduring stability, thorough investigations have been carried out to explore the possibilities presented by ‘Delafossite’ copper gallium oxide (CuGaO2). β-CuGaO2 has an ideal bandgap of 1.5 eV, along with a high absorption coefficient and excellent carrier mobility, making it well-suited for high-efficiency solar cell applications. Theoretical modelling, utilizing the optical and electrical attributes of the CuGaO2 (CGO) material, is employed to analyze its photovoltaic performance when used as an absorber. The detailed balance analysis showed 56.9% of the incident power is wasted in spectrum loss (as thermalisation and non-absorption loss), 10.1% is wasted in intrinsic losses (such as radiative recombination, radiation dilution, entropy generation etc,), extrinsic recombination (originating from electrical losses, parasitic resistance, finite mobility, surface recombination velocity (SRV), non-ohmic contacts etc), eats up another 9.5% and the resultant 23.6% is available as net useful efficiency. Through the careful selection of a suitable buffer counterpart and optimization of material parameters, absorber thickness, defect density, contacts, and SRV, the CGO device dem onstrates an efficiency of 23.6%.

Global Fight against Malaria: Goals and Achievements 1900–2022

This article examines the historical and ongoing efforts to fight malaria, a parasitic disease caused by Plasmodium species and transmitted by Anopheles mosquitoes. Despite over a century of control efforts, malaria remains a major global health issue. In 2022, there were an estimated 249 million cases across 85 countries, leading to approximately 600,000 deaths. In the recently published Global Technical Strategy for Malaria 2016–2030, the World Health Organization (WHO) has prioritized malaria eradication. The main goals are to reduce malaria incidence and mortality by 90% by 2030 compared to 2015 levels. However, as of 2022, progress has been limited, with only a 2% reduction in incidence and a 6% reduction in mortality. This review traces the historical context of malaria, highlighting its ancient origins and the pivotal scientific discoveries in the late 19th century that paved the way for modern control measures. The Global Malaria Eradication Programme launched by the WHO in 1955 initially showed promise, largely due to the insecticide DDT, but ultimately failed to achieve its goals mainly due to logistical problems, vector resistance to DDT, and inadequate funding. Despite significant advances in the early 21st century, including the Roll Back Malaria initiative and increased international funding, malaria eradication remains a distant goal. Persistent challenges, such as weak healthcare systems, parasite and vector resistance to drugs and insecticides, and inadequate funding, continue to hamper global efforts. Therefore, this article underscores the need for a deeper understanding of malaria’s history and recent evolution to inform future strategies for eradication.

Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.

Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets. However, CsA immunosuppressive nature hinders its use as an antitoxoplasmosis agent. Here, we evaluate the potential of three CsA derivatives devoid of immunosuppressive activity, namely, NIM811, Alisporivir, and dihydrocyclosporin A to target a previously characterized cyclophilin from Toxoplasma gondii (TgCyp23). We determined the X-ray crystal structures of TgCyp23 in complex with the three analogs and elucidated their binding and inhibitory properties. The high resolution of the structures revealed the precise positioning of ligands within the TgCyp23 binding site and the details of protein-ligand interactions. A comparison with the established ternary structure involving calcineurin indicates that substitutions at position 4 in CsA derivatives prevent calcineurin binding. This finding provides a molecular explanation for why CsA analogs can target Toxoplasma cyclophilins without compromising the human immune response.

In artemisinin-resistant falciparum malaria parasites, mitochondrial metabolic pathways are essential for survival but not those of apicoplast

Emergence and spread of parasite resistance to artemisinins, the first-line antimalarial therapy, threaten the malaria eradication policy. To identify therapeutic targets to eliminate artemisinin-resistant parasites, the functioning of the apicoplast and the mitochondrion was studied, focusing on the fatty acid synthesis type II (FASII) pathway in the apicoplast and the electron transfer chain in the mitochondrion. A significant enrichment of the FASII pathway among the up-regulated genes in artemisinin-resistant parasites under dihydroartemisinin treatment was found, in agreement with published transcriptomic data. However, using GC-MS analyzes of fatty acids, we demonstrated for the first time that the FASII pathway is non-functional, ruling out the use of FASII inhibitors to target artemisinin-resistant parasites. Conversely, by assessing the modulation of the oxygen consumption rate, we evidenced that mitochondrial respiration remains functional and flexible in artemisinin-resistant parasites and even at the quiescent stage. Two novel compounds targeting electron transport chain (ELQ300, ELQ400) efficiently killed quiescent artemisinin-resistant parasites. Therefore, mitochondrial respiration represents a key target for the elimination of artemisinin-resistant persistent Plasmodium falciparum parasites.

A combination of four Toxoplasma gondii nuclear-targeted effectors protects against interferon gamma-driven human host cell death.

In both mice and humans, Type II interferon gamma (IFNγ) is crucial for the regulation of Toxoplasma gondii (T. gondii) infection, during acute or chronic phases. To thwart this defense, T. gondii secretes protein effectors hindering the host's immune response. For example, T. gondii relies on the MYR translocon complex to deploy soluble dense granule effectors (GRAs) into the host cell cytosol or nucleus. Recent genome-wide loss-of-function screens in IFNγ-primed primary human fibroblasts identified MYR translocon components as crucial for parasite resistance against IFNγ-driven vacuole clearance. However, these screens did not pinpoint specific MYR-dependent GRA proteins responsible for IFNγ signaling blockade, suggesting potential functional redundancy. Our study reveals that T. gondii depends on the MYR translocon complex to prevent parasite premature egress and host cell death in human cells stimulated with IFNγ post-infection, a unique phenotype observed in various human cell lines but not in murine cells. Intriguingly, inhibiting parasite egress did not prevent host cell death, indicating this mechanism is distinct from those described previously. Genome-wide loss-of-function screens uncovered TgIST, GRA16, GRA24, and GRA28 as effectors necessary for a complete block of IFNγ response. GRA24 and GRA28 directly influenced IFNγ-driven transcription, GRA24's action depended on its interaction with p38 MAPK, while GRA28 disrupted histone acetyltransferase activity of CBP/p300. Given the intricate nature of the immune response to T. gondii, it appears that the parasite has evolved equally elaborate mechanisms to subvert IFNγ signaling, extending beyond direct interference with the JAK/STAT1 pathway, to encompass other signaling pathways as well.IMPORTANCEToxoplasma gondii, an intracellular parasite, affects nearly one-third of the global human population, posing significant risks for immunocompromised patients and infants infected in utero. In murine models, the core mechanisms of IFNγ-mediated immunity against T. gondii are consistently preserved, showcasing a remarkable conservation of immune defense mechanisms. In humans, the recognized restriction mechanisms vary among cell types, lacking a universally applicable mechanism. This difference underscores a significant variation in the genes employed by T. gondii to shield itself against the IFNγ response in human vs murine cells. Here, we identified a specific combination of four parasite-secreted effectors deployed into the host cell nucleus, disrupting IFNγ signaling. This disruption is crucial in preventing premature egress of the parasite and host cell death. Notably, this phenotype is exclusive to human cells, highlighting the intricate and unique mechanisms T. gondii employs to modulate host responses in the human cellular environment.

Influence of the Bias Voltage on Effective Electron Velocity in AlGaN/GaN High Electron Mobility Transistors.

The small-signal S parameters of the fabricated double-finger gate AlGaN/GaN high electron mobility transistors (HEMTs) were measured at various direct current quiescent operating points (DCQOPs). Under active bias conditions, small-signal equivalent circuit (SSEC) parameters such as Rs and Rd, and intrinsic parameters were extracted. Utilizing fT and the SSEC parameters, the effective electron velocity (νe-eff) and intrinsic electron velocity (νe-int) corresponding to each gate bias (VGS) were obtained. Under active bias conditions, the influence mechanism of VGS on νe-eff was systematically studied, and an expression was established that correlates νe-eff, νe-int, and bias-dependent parasitic resistances. Through the analysis of the main scattering mechanisms in AlGaN/GaN HEMTs, it has been discovered that the impact of VGS on νe-eff should be comprehensively analyzed from the aspects of νe-int and parasitic resistances. On the one hand, changes in VGS influence the intensity of polar optical phonon (POP) scattering and polarization Coulomb field (PCF) scattering, which lead to changes in νe-int dependent on VGS. The trend of νe-int with changes in VGS plays a dominant role in determining the trend of νe-eff with changes in VGS. On the other hand, both POP scattering and PCF scattering affect νe-eff through their impact on parasitic resistance. Since there is a difference in the additional scattering potential corresponding to the additional polarization charges (APC) between the gate-source/drain regions and the region under the gate, the mutual effects of PCF scattering on the under-gate electron system and the gate-source/drain electron system should be considered when adjusting the PCF scattering intensity through device structure optimization to improve linearity. This study contributes to a new understanding of the electron transport mechanisms in AlGaN/GaN HEMTs and provides a novel theoretical basis for improving device performance.

Simulation study of cadmium-free CIGS solar cell for efficiency enhancement by minimizing recombination losses through back surface field mechanism

Thin-film photovoltaic cells provide benefits over conventional first-generation technology, including lighter weight, greater flexibility, and lower power generation costs. Chalcogenide solar cells offer good efficiency and technological maturity among thin-film technology. In this work, a solar cell device structure, Al/FTO/SnS2/CIGS/CuO/Ni, is examined using SCAPS-1D. Further, by incorporating the back surface field (BSF) layer, the conversion efficiency increased from 18.93 % to 29.88 %, followed by VOC of 0.96 V, JSC of 37.07 mA cm−2, and FF of 83.71 %. This increment in device performance is owing to the lowering back surface recombination velocity and the additional hole tunnelling activity offered by the BSF layer by forming a quasi-ohmic contact, i.e. metal-semiconductor contact with negligible junction resistance relative to the total resistance of the device. Throughout this research work, the authors studied several factors such as surface recombination velocity, temperature impact, front and back contact metal work functions, parasitic resistance impact, gallium proportion, and doping density impact on CIGS solar cells. The work also included a calibration with experimental data from published sources to validate the simulation results.This paper presents a new approach for producing high-efficiency, eco-friendly CIGS solar cells with CuO back surface field mechanism.

A high content imaging assay for identification of specific inhibitors of native Plasmodium liver stage protein synthesis.

Plasmodium parasite resistance to antimalarial drugs is a serious threat to public health in malaria-endemic areas. Compounds that target core cellular processes like translation are highly desirable, as they should be capable of killing parasites in their liver and blood stage forms, regardless of molecular target or mechanism. Assays that can identify these compounds are thus needed. Recently, specific quantification of native Plasmodium berghei liver stage protein synthesis, as well as that of the hepatoma cells supporting parasite growth, was achieved via automated confocal feedback microscopy of the o-propargyl puromycin (OPP)-labeled nascent proteome, but this imaging modality is limited in throughput. Here, we developed and validated a miniaturized high content imaging (HCI) version of the OPP assay that increases throughput, before deploying this approach to screen the Pathogen Box. We identified only two hits; both of which are parasite-specific quinoline-4-carboxamides, and analogs of the clinical candidate and known inhibitor of blood and liver stage protein synthesis, DDD107498/cabamiquine. We further show that these compounds have strikingly distinct relationships between their antiplasmodial and translation inhibition efficacies. These results demonstrate the utility and reliability of the P. berghei liver stage OPP HCI assay for the specific, single-well quantification of Plasmodium and human protein synthesis in the native cellular context, allowing the identification of selective Plasmodium translation inhibitors with the highest potential for multistage activity.