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- ArticleFranzini RM, Nauer A, Scheuermann J, Neri D.Chem Commun (Camb). 2015 May 11;51(38):8014-6.Parallel affinity screening of a DNA-encoded chemical library against rat, bovine and human serum albumin allowed the identification of small-molecule ligands with distinctive binding specificities to the individual proteins.
- ArticleMaschietto M, Charlton J, Perotti D, Radice P, Geller JI, Pritchard-Jones K, Weeks M.Oncotarget. 2014 Sep 30;5(18):8014-26.It is hypothesised that Wilms tumour (WT) results from aberrant renal development due to its embryonic morphology, associated undifferentiated precursor lesions (termed nephrogenic rests) and embryonic kidney-like chromatin and gene expression profiles. From the study of overgrowth syndrome-associated WT, germline dysregulation was identified in the imprinted region at 11p15 affecting imprinted genes IGF2 and H19. This is also detected in ~70% sporadic cases, making this the most common somatic molecular aberration in WT. This review summarises the critical discussion at an international workshop held under the auspices of The European Network for Cancer Research in Children and Adolescents (ENCCA) consortium, where the potential for drug development to target IGF2 and the WT epigenome was debated. Here, we consider current cancer treatments which include targeting the IGF pathway and the use of methylation agents alone or in combination with other drugs in clinical trials of paediatric cancers. Finally, we discuss the possibility of the use of these drugs to treat patients with WT.
- ArticleProtzko J, Schooler JW.PeerJ. 2020;8:e8014.What explanation is there when teams of researchers are unable to successfully replicate already established 'canonical' findings? One suggestion that has been put forward, but left largely untested, is that those researchers who fail to replicate prior studies are of low 'expertise and diligence' and lack the skill necessary to successfully replicate the conditions of the original experiment. Here we examine the replication success of 100 scientists of differing 'expertise and diligence' who attempted to replicate five different studies. Using a bibliometric tool (h-index) as our indicator of researcher 'expertise and diligence', we examine whether this was predictive of replication success. Although there was substantial variability in replication success and in the h-factor of the investigators, we find no relationship between these variables. The present results provide no evidence for the hypothesis that systematic replications fail because of low 'expertise and diligence' among replicators.
- ArticleAbdallah HO, Ohayon YP, Chandrasekaran AR, Sha R, Fox KR, Brown T, Rusling DA, Mao C, Seeman NC.Chem Commun (Camb). 2016 Jun 28;52(51):8014-7.The tensegrity triangle is a robust DNA motif that can self-assemble to generate macroscopic three-dimensional crystals. However, the stability of these crystals is dependent on the high ionic conditions used for crystal growth. Here we demonstrate that a triplex-forming oligonucleotide can be used to direct the specific intercalation, and subsequent photo-cross-linking, of 4,5',8-trimethylpsoralen to single or multiple loci within or between the tiles of the crystal. Cross-linking between the tiles of the crystal improves their thermal stability. Such an approach is likely to facilitate the removal of crystals from their mother liquor and may prove useful for applications that require greater crystal stability.
- ArticleSun C, VanRaden PM, O'Connell JR, Weigel KA, Gianola D.J Dairy Sci. 2013;96(12):8014-23.Computerized mating programs using genomic information are needed by breed associations, artificial-insemination organizations, and on-farm software providers, but such software is already challenged by the size of the relationship matrix. As of October 2012, over 230,000 Holsteins obtained genomic predictions in North America. Efficient methods of storing, computing, and transferring genomic relationships from a central database to customers via a web query were developed for approximately 165,000 genotyped cows and the subset of 1,518 bulls whose semen was available for purchase at that time. This study, utilizing 3 breeds, investigated differences in sire selection, methods of assigning mates, the use of genomic or pedigree relationships, and the effect of including dominance effects in a mating program. For both Jerseys and Holsteins, selection and mating programs were tested using the top 50 marketed bulls for genomic and traditional lifetime net merit as well as 50 randomly selected bulls. The 500 youngest genotyped cows in the largest herd in each breed were assigned mates of the same breed with limits of 10 cows per bull and 1 bull per cow (only 79 cows and 8 bulls for Brown Swiss). A dominance variance of 4.1 and 3.7% was estimated for Holsteins and Jerseys using 45,187 markers and management group deviation for milk yield. Sire selection was identified as the most important component of improving expected progeny value, followed by managing inbreeding and then inclusion of dominance. The respective percentage gains for milk yield in this study were 64, 27, and 9, for Holsteins and 73, 20, and 7 for Jerseys. The linear programming method of assigning a mate outperformed sequential selection by reducing genomic or pedigree inbreeding by 0.86 to 1.06 and 0.93 to 1.41, respectively. Use of genomic over pedigree relationship information provided a larger decrease in expected progeny inbreeding and thus greater expected progeny value. Based on lifetime net merit, the economic value of using genomic relationships was >$3 million per year for Holsteins when applied to all genotyped females, assuming that each will provide 1 replacement. Previous mating programs required transferring only a pedigree file to customers, but better service is possible by incorporating genomic relationships, more precise mate allocation, and dominance effects. Economic benefits will continue to grow as more females are genotyped.
- ArticleMedepalli VM, Davis LS, Medepalli LC, Padala SA.Cureus. 2020 May 07;12(5):e8014.Calciphylaxis, also referred to as calcific uremic arteriolopathy, is a rare, life-threatening cutaneous systemic disease that typically occurs in the setting of end-stage renal disease (ESRD). ESRD is the most recognized risk factor for calciphylaxis but it is not the sole risk factor. Calciphylaxis has also been associated with liver cirrhosis with or without concurrent renal disease. The current case describes a patient who developed calciphylaxis in the setting of hemodialysis, liver cirrhosis, and atrial fibrillation managed with warfarin therapy, all risk factors for calciphylaxis. The need for alternatives to warfarin therapy, specifically in patients with atrial fibrillation on hemodialysis for ESRD who are at increased risk for calciphylaxis, is discussed. Specifically, the left atrial appendage occluder device is described and the need for interdisciplinary management of these patients is stressed.
- ArticleWang Y, Li F, Wei S, Li W, Wu J, Li S, Hu X, Tang T, Liu X.Int J Nanomedicine. 2024;19:7997-8014.Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.
Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.
Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.
Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury. - ArticleWu S, Han S, Han J, Su X.Chem Commun (Camb). 2014 Jul 28;50(59):8014-7.A photothermal pH-reporting nanoprobe was developed for intraoperative tumor detection by "turn-on" fluorescence of the probe inside viable tumor cells, photothermal tumor therapy, and in situ monitoring of tumor killing by non-fluorescence of the probe in damaged cells.
- ArticleManfredi F, Stasi L, Buonanno S, Marzuttini F, Noviello M, Mastaglio S, Abbati D, Potenza A, ... Show More Balestrieri C, Cianciotti BC, Tassi E, Feola S, Toffalori C, Punta M, Magnani Z, Camisa B, Tiziano E, Lupo-Stanghellini MT, Branca RM, Lehtiö J, Sikanen TM, Haapala MJ, Cerullo V, Casucci M, Vago L, Ciceri F, Bonini C, Ruggiero E.Sci Adv. 2023 12;9(48):eadg8014.To study and then harness the tumor-specific T cell dynamics after allogeneic hematopoietic stem cell transplant, we typed the frequency, phenotype, and function of lymphocytes directed against tumor-associated antigens (TAAs) in 39 consecutive transplanted patients, for 1 year after transplant. We showed that TAA-specific T cells circulated in 90% of patients but display a limited effector function associated to an exhaustion phenotype, particularly in the subgroup of patients deemed to relapse, where exhausted stem cell memory T cells accumulated. Accordingly, cancer-specific cytolytic functions were relevant only when the TAA-specific T cell receptors (TCRs) were transferred into healthy, genome-edited T cells. We then exploited trogocytosis and ligandome-on-chip technology to unveil the specificities of tumor-specific TCRs retrieved from the exhausted T cell pool. Overall, we showed that harnessing circulating TAA-specific and exhausted T cells allow to isolate TCRs against TAAs and previously not described acute myeloid leukemia antigens, potentially relevant for T cell-based cancer immunotherapy.
- ArticleAbu-Elnasr Awwad A, Hasan RA, Hablas MGA, Mohammad Mohammad Abdelhay O, Dawood YMA, ... Show More Ahmed Mohamed B, Rabou KAA, Salem TMM, Elhady M, Abd El-Aal GN, Ahmed AHE, Ibrahim Mostafa Hasan A, Elmadbouly AAE, Yahia MB, Ashry WMO, El Sayed SSMM, Algendy AMM, Alkot AMF, Farag MF, El Shenawy Emara AAA, Elbayoumy FMAE, Ali HF, Aldesoky MM, Abd-Eltwab RA, Manawy SM, Mohamed Faruk E.Sci Rep. 2023 05 17;13(1):8014.Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children's patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case-control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3-6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group (P < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group (P < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant (P = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group (P < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children.
- ArticleWang ZX, Shi WM, Bi HY, Li XH, Su GF, Mo DL.J Org Chem. 2016 09 02;81(17):8014-21.A metal-free method for synthesis of N-(2-hydroxyaryl)benzotriazoles via O-arylation of N-hydroxybenzotriazoles with readily available diaryliodonium salts and sequential N-O bond cleavage under mild conditions has been developed. The [3,3]-rearrangement of N-O bond cleavage could take place on the N instead of C atom. The reaction was compatible with diverse functional groups and a new type of P,N-ligand was synthesized in three steps.
- ArticleRavikumar A, Kladnik G, Müller M, Cossaro A, Bavdek G, Patera LL, Sánchez-Portal D, Venkataraman L, Morgante A, Brivio GP, Cvetko D, Fratesi G.Nanoscale. 2018 May 03;10(17):8014-8022.We compare the ultrafast charge transfer dynamics of molecules on epitaxial graphene and bilayer graphene grown on Ni(111) interfaces through first principles calculations and X-ray resonant photoemission spectroscopy. We use 4,4'-bipyridine as a prototypical molecule for these explorations as the energy level alignment of core-excited molecular orbitals allows ultrafast injection of electrons from a substrate to a molecule on a femtosecond timescale. We show that the ultrafast injection of electrons from the substrate to the molecule is ∼4 times slower on weakly coupled bilayer graphene than on epitaxial graphene. Through our experiments and calculations, we can attribute this to a difference in the density of states close to the Fermi level between graphene and bilayer graphene. We therefore show how graphene coupling with the substrate influences charge transfer dynamics between organic molecules and graphene interfaces.
- ArticleGanguli P, Singh B, Reddy NN, Raut A, Mishra D, Das BS.Sci Rep. 2022 05 15;12(1):8014.Most land surface system models and observational assessments ignore detailed soil characteristics while describing the drought attributes such as growth, duration, recovery, and the termination rate of the event. With the national-scale digital soil maps available for India, we assessed the climate-catchment-soil nexus using daily observed streamflow records from 98 sites in tropical rain-dominated catchments of peninsular India (8-25° N, 72-86° E). Results indicated that climate-catchment-soil properties may control hydrological drought attributes to the tune of 14-70%. While terrain features are dominant drivers for drought growth, contributing around 50% variability, soil attributes contribute ~ 71.5% variability in drought duration. Finally, soil and climatic factors together control the resilience and termination rate. The most relevant climate characteristics are potential evapotranspiration, soil moisture, rainfall, and temperature; temperature and soil moisture are dominant controls for streamflow drought resilience. Among different soil properties, soil organic carbon (SOC) stock could resist drought propagation, despite low-carbon soils across the Indian subcontinent. The findings highlight the need for accounting feedback among climate, soil, and topographical properties in catchment-scale drought propagations.
- ArticleEerkens HJ, Buters FM, Weaver MJ, Pepper B, Welker G, Heeck K, Sonin P, de Man S, Bouwmeester D.Opt Express. 2015 Mar 23;23(6):8014-20.For experimental investigations of macroscopic quantum superpositions and the possible role of gravitational effects on the reduction of the corresponding quantum wave function it is beneficial to consider large mass, low frequency optomechanical systems. We report optical side-band cooling from room temperature for a 1.5×10⁻¹⁰ kg (mode mass), low frequency side-band resolved optomechanical system based on a 5 cm long Fabry-Perot cavity. By using high-quality Bragg mirrors for both the stationary and the micromechanical mirror we are able to construct an optomechanical cavity with an optical linewidth of 23 kHz. This, together with a resonator frequency of 315 kHz, makes the system operate firmly in the side-band resolved regime. With the presented optomechanical system parameters cooling close to the ground state is possible. This brings us one step closer to creating and verifying macroscopic quantum superpositions.
- ArticleVinck E, Carter E, Murphy DM, Van Doorslaer S.Inorg Chem. 2012 Aug 06;51(15):8014-24.The interactions of a weak organic acid (acetic acid, HOAc) with a toluene solution of the Co(II)-Schiff base type complex, (R,R')-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamino Co(II) (labeled [Co(1)]), was investigated using EPR, HYSCORE, and DFT computations. This activated [Co(II)(1)] system is extremely important within the context of asymmetric catalysts (notably the hydrolytic kinetic resolution of epoxides) despite the lack of detailed structural information about the nature of the paramagnetic species present. Under anaerobic conditions, the LS [Co(II)(1)] complex with a |yz, (2)A(2)〉 ground state is converted into a low-spin (LS) and a high-spin (HS) complex in the presence of the acid. The newly formed LS state is assigned to the coordinated [Co(II)(1)]-(HOAc) complex, possessing a |z(2), (2)A(1)〉 ground state (species A; g(x) = 2.42, g(y) = 2.28, g(z) = 2.02, A(x) = 100, A(y) = 120, A(z) = 310 MHz). The newly formed HS state is assigned to an acetate coordinated [Co(II)(1)]-(OAc(-)) complex, possessing an S = 3/2 spin ground state (species B, responsible for a broad EPR signal with g ≈ 4.6). These spin ground states were confirmed with DFT calculations using the hybrid BP86 and B3LYP functionals. Under aerobic conditions, the LS and HS complexes (species A and B) are not observed; instead, a new HS complex (species C) is formed. This complex is tentatively assigned to a paramagnetic superoxo bridged dimer (AcO(-))[Co(II)(1)···O(2)(-)Co(III)(1)](HOAc), as distinct from the more common diamagnetic peroxo bridged dimers. Species C is characterized by a very broad HS EPR signal (g(x) = 5.1, g(y) = 3.9, g(z) = 2.1) and is reversibly formed by oxygenation of the LS [Co(II)(1)]-(HOAc) complex to the superoxo complex [Co(III)(1)O(2)(-)](HOAc), which subsequently forms the association complex C by interaction with the HS [Co(II)(1)](OAc(-)) species. The LS and HS complexes were also identified using other organic acids (benzoic and propanoic acid). Thermal annealing-quenching experiments revealed the additional presence of [Co(III)(1)O(2)(-)](HOAc) adducts, corroborating the presence of species C and the presence of diamagnetic dimer complexes in the solution, such as the EPR silent (HOAc)[Co(III)(1)(O(2)(2-))Co(III)(1)](HOAc). Overall, it appears that a facile interconversion of the [Co(1)] complex, possessing a LS ground state, occurs in the presence of acetic acid, producing both HS and LS Co(II) states, prior to formation of the oxidized active form of the catalyst, [Co(III)(1)](OAc(-)).
- ArticlePal KB, Basnet BB, Pant RR, Bishwakarma K, Kafle K, Dhami N, Sharma ML, Thapa LB, Bhattarai B, Bhatta YR.Heliyon. 2021 Sep;7(9):e08014.The academic sectors are badly affected by the COVID-19 pandemic globally. The studies regarding the implications of COVID-19 in education in Nepal were minimal, thus, this paper aims to highlight the impacts of the pandemic on the education sector of Nepal. It is revealed that the Nepalese academia has been facing problems due to lack of adequate and appropriate sustainable infrastructure for the online system, including skilled human resources. In addition, limited internet facilities in remote and rural areas were the other challenging tasks for virtual academic activities. Therefore, the concerned stakeholders should provide necessary services and appropriate strategies for virtual means of the education system to compensate the repercussion caused by the pandemic. This study could be helpful to identify the critical needs emerged due to the pandemic at present and in future and also contribute to adopt appropriate policy for the revival of educational institutions.
- ArticleYi Z, Trellenkamp S, Offenhäusser A, Mayer D.Chem Commun (Camb). 2010 Nov 14;46(42):8014-6.Electrostatically linked ferrocene junctions were assembled and their conductance was investigated on the level of individual molecules by means of an electrochemical mechanical break junction. Conductance histograms of repeatedly formed molecular junctions showed peaks at multiples of 3.4 × 10(-5) G(0), which is one order of magnitude smaller than the conductance reported for covalently linked cysteamine-ferrocene-cysteamine.
- ArticleSantos RMD, Sousa LE, Galvão DS, Ribeiro LA.Sci Rep. 2020 May 15;10(1):8014.Penta-graphene is a quasi-two-dimensional carbon allotrope consisting of a pentagonal lattice in which both sp2 and sp3-like carbons are present. Unlike graphene, penta-graphene exhibits a non-zero bandgap, which opens the possibility of its use in optoelectronic applications. However, as the observed bandgap is large, gap tuning strategies such as doping are required. In this work, density functional theory calculations are used to determine the effects of the different number of line defects of substitutional nitrogen or silicon atoms on the penta-graphene electronic behavior. Our results show that this doping can induce semiconductor, semimetallic, or metallic behavior depending on the doping atom and targeted hybridization (sp2 or sp3-like carbons). In particular, we observed that nitrogen doping of sp2-like carbons atoms can produce a bandgap modulation between semimetallic and semiconductor behavior. These results show that engineering line defects can be an effective way to tune penta-graphene electronic behavior.
- ArticleSawadikiat P, Setwipattanachai P, Chaiseri S, Hongsprabhas P.J Food Sci Technol. 2015 Dec;52(12):8014-22.This study investigated the effects of evaporating temperature during molecular distillation (MD) process employed to deodorizer distillate (DD) on the retention of rice phytochemicals in the unevaporated fraction (UMDs), which were then further used as co-surfactants in the fabrication of water-dispersible vesicles. The pilot-scale MD unit was operated at 120, 140 or 160 °C and 0.1 Pa to concentrate rice phytosterols from 1540.8 mg in 100 g DD to 3990.2-4904.8 mg in 100 g UMDs by evaporating out free fatty acids. Although γ-oryzanol content was increased from 598.9 mg in 100 g DD to 870.0-1018.1 mg in 100 g UMDs when the temperature was raised to 160 °C, such high temperature decreased tocols from 2185.7 mg in 100 g DD to 850.5 mg in 100 g UMDs and antioxidant capacity of UMDs measured as 2,2-diphenyl-1-picrylhydrazyl scavenging capacity. The UMD obtained after distillation at 140 °C was used as co-surfactant with soy lecithin, sucrose palmitate or polyoxyethylene sorbitan monooleate (Tween 80) to fabricate vesicles in pH 7.0 phosphate buffered saline (PBS). This study showed potential use of the UMD as a source of rice phytochemicals and a co-surfactant when used with Tween80 in small vesicle fabrication. The fabricated Tween 80/UMD vesicles in PBS had the size range of 200-300 nm and were stable within a temperature range of 4 to 37 °C for 96 h.
- ArticleHaidl H, Pohl S, Leschnik B, Gallistl S, Muntean W, Schlagenhauf A.Sci Rep. 2019 05 29;9(1):8014.Healthy neonates exhibit a well-functioning haemostatic system despite peculiarities regarding composition of clotting factors and inhibitors as well as impaired platelet aggregation. Thrombocytopenia and severe bleeding events are feared in sick infants. Recombinant factor VIIa (rFVIIa) is a haemostatic agent used as a last resort in neonates with refractory bleedings. Aim of this study was to investigate in-vitro (i) changes in thrombin generation with different platelet counts, (ii) effects of rFVIIa under conditions of thrombocytopenia and (iii) potentially differing dose-response of rFVIIa in cord blood as a surrogate for neonatal blood compared to adult blood. Thrombin generation parameters were observed in cord blood plasma and adult plasma with various platelet counts, with or without addition of rFVIIa, respectively. Low platelet counts did not influence thrombin generation in cord blood in contrast to adult blood. RFVIIa primarily affected lag time throughout all platelet concentrations. Interestingly, peak height was reduced exclusively in cord blood plasma after addition of rFVIIa. No significant differences regarding dose-response were observed between cord blood and adult blood. In contrast to adult blood, thrombocytopenia in cord blood does not significantly influence thrombin generation. Even at very low platelet counts there is enough negatively charged surface to support rFVIIa action in plasma from cord blood and adult blood in-vitro.