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  • Article
    Xochipiltecatl D, Baixeras J, Cordero CR.
    PeerJ. 2021;9:e12499.
    Monandrous species are rare in nature, especially in animals where males transfer nutrients to females in the ejaculate. The proximate mechanisms responsible for monandry are poorly studied. In butterflies and moths, the male transfers a nutritious spermatophore into the corpus bursae (CB) of the female. The CB is a multifunctional organ that digests the spermatophore and has partial control of the post-mating sexual receptivity of the female. The spermatophore distends the CB and the post-mating sexual receptivity of the female is inversely proportional to the degree of distension. The CB of many butterfly species has a muscular sheath whose contractions mechanically contribute to digest the spermatophore. As the contents of the CB are absorbed, the degree of distension decreases and the female recovers receptivity. We studied the monandrous butterfly Leptophobia aripa (Boisduval, 1836) (Pieridae) and found that females do not digest the spermatophores. We investigated the structure of the CB and found that a muscular sheath is absent, indicating that in this butterfly females lack the necessary "apparatus" for the mechanical digestion of the spermatophore. We propose that female monandry in this species is result of its incapability to mechanically digest the spermatophore, which results in a constant degree of CB distension after mating and, thus, in the maintenance of the sexually unreceptive state of females. Hypotheses on the evolution of this mechanism are discussed.
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  • Article
    Schuurman HJ, Bühler L.
    Xenotransplantation. 2019 01;26(1):e12499.
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  • Article
    Saeidi C, van der Weide D.
    Opt Express. 2014 May 19;22(10):12499-504.
    Modeling a nanoparticle array (NPA) inside a thin glass slab as a lumped optical resonator, we propose a systematic approach to design for an efficient optical filter with bandwidth tunability. The quality factor and bandwidth of the resonator are related to the physical, geometrical, and electrical parameters of an NPA and its surrounding medium, whose permittivity is varied to change the bandwidth. We propose a structure amenable to our design approach consisting of an NPA slab surrounded by liquid crystal whose permittivity can be altered. We validate the design procedure with examples of tunable-bandwidth filters at different frequency regimes from NIR to blue.
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  • Article
    Negri R, Baranyai Z, Tei L, Giovenzana GB, Platas-Iglesias C, Bényei AC, Bodnár J, Vágner A, Botta M.
    Inorg Chem. 2014 Dec 01;53(23):12499-511.
    The heptadentate ligand OBETA (2,2'-oxybis(ethylamine)-N,N,N',N'-tetraacetic acid) was reported to form complexes with Ln(3+) ions more stable than those formed by the octadentate and more popular congener EGTA (ethylene glycol O,O'-bis(ethylamine)-N,N,N',N'-tetraacetic acid). The structural features leading to this puzzling coordination paradox were investigated by X-ray diffraction, solution state NMR, molecular modeling, and relaxometric studies. The stability constant of Gd(OBETA) (log KGdL = 19.37, 0.1 M KCl) is 2 orders of magnitude higher than that of the higher denticity analogue Gd(EGTA) (log KGdL = 17.66, 0.1 M KCl). The half-lives (t1/2) for the dissociation reactions of Gd(OBETA) and Gd(EGTA) ([Cu(2+)]tot = 0.2 mM, [Cit(3-)]tot = 0.5 mM, [PO4(3-)]tot = 1.0 mM, and [CO3(2-)]tot = 25 mM at pH = 7.4 and 25 °C in 0.1 M KCl solution) are 6.8 and 0.63 h, respectively, reflecting the much higher inertness of Gd(OBETA) near physiological conditions. NMR studies and DFT calculations using the B3LYP functional and a large-core ECP indicate that the [Gd(OBETA)(H2O)2](-) complex most likely exists in solution as the Δ(λλ)(δδδδ)A/Λ(δδ)(λλλλ)A enantiomeric pair, with an activation free energy for the enantiomerization process of ∼40 kJ·mol(-1). The metal ion is nine-coordinate by seven donor atoms of the ligand and two inner-sphere water molecules. The X-ray crystal structure of [C(NH2)3]3[Lu(OBETA)(CO3)]·2H2O is in agreement with the predictions of DFT calculations, the two coordinated water molecules being replaced by a bidentate carbonate anion. The (1)H NMRD and (17)O NMR study revealed that the two inner-sphere water molecules in Gd(OBETA) are endowed with a relatively fast water exchange rate (kex(298) = 13 × 10(6) s(-1)). The higher thermodynamic stability and inertness of Ln(OBETA) complexes, peaking in the center of the 4f series, combined with the presence of two coordinated water molecules suggests that Gd(OBETA) is a promising paramagnetic probe for MRI applications.
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  • Article
    Mohajane C, Manjoro M.
    Heliyon. 2022 Dec;8(12):e12499.
    Sediment contamination by heavy metals poses one of the worst environmental risks to aquatic ecosystems worldwide. The study explored sediment-associated heavy metal contamination and potential ecological risk along the Molopo River in Mahikeng, South Africa. Total concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn) were analysed using inductively coupled plasma mass spectrometry. Various indices were applied to assess the level of contamination and ecological risk. Most heavy metal concentrations at selected upstream and downstream sites were below average shale, except Cr, Cu, Hg, Pb, and Zn. The contamination factor (CF) indicates that the level of contamination was low (CF < 1) at most sampling sites, except Cr, Cu, Pb and Zn, which varied from moderate (1 CF < 3) to considerable (3 ≤ CF < 6) contamination. The enrichment factor (EF) shows that Cd, Cr, Cu, and Zn were moderate (2 EF < 5) to significantly enriched (5 EF < 20) at the affected sites. The results suggest anthropogenic enrichment (EF > 2) of Cd, Cr, Cu, and Zn. The threshold effect concentration and probable effect concentration sediment quality guidelines predicted that Cr, Cu, and Ni concentrations were more likely to have harmful effects on bottom-dwelling organisms. Pearson correlation and principal component analysis reveal that Cd, Cr, Cu, Ni, Pb, and Zn had a common anthropogenic source. We attribute the source to industrial and wastewater effluent, vehicle traffic, and runoff from various urban surfaces in the city. The study provides baseline data for heavy metal monitoring in the study area. Future research and monitoring should focus on heavy metals that cause concern because of their concentrations (Cr, Cu, Pb, and Zn) and potential ecological risk (Cr, Cu, and Ni).
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  • Article
    Calanni JS, Aranda ML, Dieguez HH, Dorfman D, Schmidt TM, Rosenstein RE.
    Sci Rep. 2024 05 31;14(1):12499.
    In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > >  > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.
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  • Article
    Sturza M, Daviero-Minaud S, Huvé M, Renaut N, Tiercelin N, Mentré O.
    Inorg Chem. 2011 Dec 19;50(24):12499-507.
    The (Ba,Sr)FeO(3-δ) system is known for its strong tendency for oxygen and vacancies to order into several forms including fully ordered pseudobrownmillerites, hexagonal perovskites with segregation of the vacancies in particular anionic layers and low deficient (pseudo)cubic compounds (generally δ < 0.27, Fe(3/4+)). We show for the first time, using a simple chemical process, the easy access to a large amount of vacancies (δ ≈ 0.5, Fe(3+)) within the room-temperature stable tetragonal (pseudocubic) Sr(0.8)Ba(0.2)FeF(~0.1)(O,F)(~2.5.) The drastic effect of the incorporation of a minor amount of fluoride passes through the repartition of local O/F/□ constraints shifting the tolerance factor into the pseudocubic range for highly deficient compounds. It is stable up to 670 K, where an irreversible reoxidation process occurs, leading to the cubic-form. The comparison with the cubic oxide Sr(0.8)Ba(0.2)FeO(~2.7) shows the increase of the resistivity (3D-VRH model) by two decades due to the almost single valent Fe(3+) of the oxofluoride. In addition, the G-type magnetic ordering shows relatively weak moment for Fe(3+) cations (M(Fe) ≈ 2.64(1) μB at room temperature) attributed to incoherent magnetic components expected from local disorder in such anionic-deficient compounds.
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  • Article
    Aono AH, Ferreira RCU, Moraes ADCL, Lara LAC, Pimenta RJG, Costa EA, Pinto LR, Landell MGA, Santos MF, Jank L, Barrios SCL, do Valle CB, Chiari L, Garcia AAF, Kuroshu RM, Lorena AC, Gorjanc G, de Souza AP.
    Sci Rep. 2022 07 21;12(1):12499.
    Poaceae, among the most abundant plant families, includes many economically important polyploid species, such as forage grasses and sugarcane (Saccharum spp.). These species have elevated genomic complexities and limited genetic resources, hindering the application of marker-assisted selection strategies. Currently, the most promising approach for increasing genetic gains in plant breeding is genomic selection. However, due to the polyploidy nature of these polyploid species, more accurate models for incorporating genomic selection into breeding schemes are needed. This study aims to develop a machine learning method by using a joint learning approach to predict complex traits from genotypic data. Biparental populations of sugarcane and two species of forage grasses (Urochloa decumbens, Megathyrsus maximus) were genotyped, and several quantitative traits were measured. High-quality markers were used to predict several traits in different cross-validation scenarios. By combining classification and regression strategies, we developed a predictive system with promising results. Compared with traditional genomic prediction methods, the proposed strategy achieved accuracy improvements exceeding 50%. Our results suggest that the developed methodology could be implemented in breeding programs, helping reduce breeding cycles and increase genetic gains.
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  • Article
    Liang Q, Chang B, Brulois KF, Castro K, Min CK, Rodgers MA, Shi M, Ge J, Feng P, Oh BH, Jung JU.
    J Virol. 2013 Nov;87(22):12499-503.
    Autophagy is an important innate safeguard mechanism for protecting an organism against invasion by pathogens. We have previously discovered that Kaposi's sarcoma-associated herpesvirus (KSHV) evades this host defense through tight suppression of autophagy by targeting multiple steps of autophagy signal transduction. Here, we report that KSHV K7 protein interacts with Rubicon autophagy protein and inhibits the autophagosome maturation step by blocking Vps34 enzymatic activity, further highlighting how KSHV deregulates autophagy-mediated host immunity for its life cycle.
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  • Article
    Müller M, Kessler B.
    Langmuir. 2011 Oct 18;27(20):12499-505.
    Deposition from dopamine (DA) solutions at germanium (Ge) model substrates was monitored under stationary conditions using surface sensitive in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR spectra of the interfacial organic layer formed upon contact of TRIS buffered aqueous DA solutions to a Ge internal reflection element (IRE) showed conveniently strong diagnostic IR absorption bands, which were increasing with deposition time up to at least 6 h. Comparison of IR spectra of unreacted pristine DA, surface reacted, and bulk reacted material confirmed chemical reactions of DA to a polymerizate according to the literature. The found IR bands could be assigned to aromatic as well as C-O single bond moieties. The kinetic courses of the diagnostic band integrals showed an initial increase and saturation of the deposition after around 300 min, which could be empirically represented by an exponential damping function revealing a rather small kinetic constant. Highest deposition levels were found at pH = 8.5 (TRIS buffer or NaOH) in contrast to pH = 6.2, where no deposition occurred. Minor deposition was found in the presence of salt or at ZnSe instead of Ge due to the absence of reactive hydroxyl groups. The concentration dependence of DA deposition showed an initial increase and a saturation beginning at around 0.4 mg/mL (0.0022 M), where around 50 nm thick films featuring granular surface morphologies are formed. The adsorbed species are suggested to be smaller bulk reacted DA polymerizate particles with reactive end groups. Rinsing the formed films by pure TRIS buffer resulted in a time dependent release of deposited organic material by ≈23%, which could be represented by an exponential decay function. A saturation of the release after around 100 min and a larger kinetic constant compared to deposition could be determined. The released material is suggested to be larger aggregated bulk reacted DA polymerizate particles loosely bound to the surface by weak interaction forces.
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  • Article
    He C, Duan X, Guo N, Chan C, Poon C, Weichselbaum RR, Lin W.
    Nat Commun. 2016 08 17;7:12499.
    Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.
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  • Article
    Viana PF, Ezaz T, de Bello Cioffi M, Liehr T, Al-Rikabi A, Goll LG, Rocha AM, Feldberg E.
    Sci Rep. 2020 07 27;10(1):12499.
    Most of snakes exhibit a ZZ/ZW sex chromosome system, with different stages of degeneration. However, undifferentiated sex chromosomes and unique Y sex-linked markers, suggest that an XY system has also evolved in ancestral lineages. Comparative cytogenetic mappings revealed that several genes share ancestry among X, Y and Z chromosomes, implying that XY and ZW may have undergone transitions during serpent's evolution. In this study, we performed a comparative cytogenetic analysis to identify homologies of sex chromosomes across ancestral (Henophidia) and more recent (Caenophidia) snakes. Our analysis suggests that, despite ~ 85 myr of independent evolution, henophidians and caenophidians retained conserved synteny over much of their genomes. However, our findings allowed us to discover that ancestral and recent lineages of snakes do not share the same sex chromosome and followed distinct pathways for sex chromosomes evolution.
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  • Article
    Bai Y, Wang G, Cheng Y, Shi P, Yang C, Yang H, Xu Z.
    Sci Rep. 2019 08 29;9(1):12499.
    Studying the obstacles associated with continuous cropping is necessary for sustainable agricultural production. Phenolic acids play an important role in continuous cropping systems, although their mechanism of action in these systems remains unclear. Using High-performance Liquid Chromatography, we characterized the changes in phenolic acid contents in soils that had been continuously cropped with tobacco for different time periods and evaluated the interactions between soil physicochemical properties, bacterial community structure and diversity, and phenolic acids. Prolonged continuous cropping was associated with a significant increase in the content of phenolic acids and a significant decrease in soil pH and bacterial diversity. A significant negative correlation between pH and phenolic acids content was observed, suggesting that soil acidification potentially leads to the accumulation of phenolic acids. The Mantel test indicated that phenolic acids were positively associated with relative bacterial abundance (R = 0.480, P < 0.01), signifying that the accumulation of phenolic acids is a potential factor leading to changes in bacterial community structure. Continuous cropping lowered the soil pH, which stimulated phenolic acid accumulation and consequently altered the bacterial community structure and diversity, ultimately impacting tobacco plant growth.
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  • Article
    López-Alarcón M, Inda-Icaza P, Márquez-Maldonado MC, Armenta-Álvarez A, Barbosa-Cortés L, Maldonado-Hernández J, Piña-Aguero M, Barradas-Vázquez A, Núñez-García BA, Rodríguez-Cruz M, Fernández JR.
    Pediatr Obes. 2019 05;14(5):e12499.
    BACKGROUND: Paediatric obesity and insulin resistance (IR) are potentially reversible inflammatory conditions. Long chain polyunsaturated fatty acids omega-3 (LCPUFA-ω3) show anti-inflammatory and metabolic properties, but their clinical efficacy is unclear.
    OBJECTIVE: The objective of this study is to evaluate whether supplementation with LCPUFA-ω3 for 3 months reduces insulin resistance and weight to adolescents with obesity.
    METHODS: Double-blind trial of 366 adolescents with obesity randomly assigned to 1.2-g LCPUFA-ω3 (DO3) or 1-g sunflower oil (DP) daily for 3 months; both groups received an energy-restricted diet. Children attended monthly for anthropometric, dietary, and clinical measurements. Basal and final blood samples were obtained to measure metabolic markers and erythrocytes fatty acids. Regression models were used for analysis.
    RESULTS: A total of 119 DO3 and 126 DP children completed follow-up. At baseline, 92% of children presented IR, 66% hypertriglyceridemia, 37% low-grade inflammation, and 32% metabolic syndrome. Despite erythrocytes LCPUFA-ω3 increased more in DO3 (Median differences = 0.984 w/w%; 95 IC = 0.47, 1.53, P < 0.001), body weight, insulin, and HOMA changed similarly in both groups at the end of intervention. Adjusting for basal values, changes in weight, insulin, and HOMA was not related with supplementation.
    CONCLUSIONS: Supplementation with LCPUFA-ω3 does not affect body weight or insulin in adolescents with obesity.
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  • Article
    Simon DM, Nidiffer AR, Wallace MT.
    Sci Rep. 2018 08 21;8(1):12499.
    Asynchronous arrival of audiovisual information at the peripheral sensory organs is a ubiquitous property of signals in the natural environment due to differences in the propagation time of light and sound. As these cues are constantly changing their distance from the observer, rapid adaptation to asynchronies is crucial for their appropriate integration. We investigated the neural basis of rapid recalibration to asynchronous audiovisual speech in humans using a combination of psychophysics, drift diffusion modeling, and electroencephalography (EEG). Consistent with previous reports, we found that perception of audiovisual temporal synchrony depends on the temporal ordering of the previous trial. Drift diffusion modelling indicated that this recalibration effect is well accounted for by changes in the rate of evidence accumulation (i.e. drift rate). Neural responses as indexed via evoked potentials were similarly found to vary based on the temporal ordering of the previous trial. Within and across subject correlations indicated that the observed changes in drift rate and the modulation of evoked potential magnitude were related. These results indicate that the rate and direction of evidence accumulation are affected by immediate sensory history and that these changes contribute to single trial recalibration to audiovisual temporal asynchrony.
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  • Article
    Robotis J, Tsiodras S, Rokkas T.
    Helicobacter. 2018 Aug;23(4):e12499.
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  • Article
    Nitta T, Hofacre A, Hull S, Fan H.
    J Virol. 2009 Dec;83(23):12499-511.
    Jaagsiekte sheep retrovirus (JSRV) is a simple betaretrovirus causing a contagious lung cancer of sheep. JSRV encodes unspliced and spliced viral RNAs, among which unspliced RNA encodes Gag and Pol proteins and a singly spliced mRNA encodes Env protein. In another study we found that JSRV encodes a regulatory protein, Rej, that is responsible for synthesis of Gag polyprotein from unspliced viral RNA. Rej is encoded in the 5' end of env, and it enhances nuclear export or accumulation of cytoplasmic unspliced viral RNA in 293T cells but not in most other cell lines (A. Hofacre, T. Nitta, and H. Fan, J. Virol. 83:12483-12498, 2009). In this study, we found that mutations in the 3' end of env in the context of a cytomegalovirus-driven full-length JSRV expression construct abolished Gag protein synthesis and released viruses in 293T cells. These mutants also showed deficits in accumulation of unspliced viral RNA in the cytoplasm. These mutants defined a Rej-responsive element (RejRE). Inhibition of CRM1 but not Tap function prevented nuclear export/accumulation of cytoplasmic unspliced RNA in 293T cells, similarly to other complex retroviruses that express analogous regulator proteins (e.g., human immunodeficiency virus Rev). Structural modeling of the RejRE with Zuker M-fold indicated a region with a predicted stable secondary structure. Mutational analysis in this region indicated the importance of both secondary structures and primary nucleotide sequences in a central stem-bulge-stem structure. In contrast to 293T cells, mutations in the RejRE did not affect the levels of cytoplasmic unspliced RNA in 293 cells, although the unspliced RNA showed partial degradation, perhaps due to lack of translation. RejRE-containing RNA relocalized Rej protein from the nucleus to the cytoplasm in 293 and rat 208F cells, suggesting binding of Rej to the RejRE.
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  • Article
    Blanco-Rojo R, Perez-Martinez P, Lopez-Moreno J, Martinez-Botas J, Delgado-Lista J, van-Ommen B, Yubero-Serrano E, Camargo A, Ordovas JM, Perez-Jimenez F, Gomez-Coronado D, Lopez-Miranda J.
    Sci Rep. 2017 10 02;7(1):12499.
    This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495-0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511-0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (β = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function.
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  • Article
    Kesserwani H.
    Cureus. 2021 Jan 05;13(1):e12499.
    The thalamus is a complex structure with over 40 named nuclei. Ischemic lesions of the thalamus exhibit a panorama of phenomena ranging from facial numbness to ocular and visual field disturbances to hemiplegia, behavioral disorders, and stupor. It is a dense neuronal hub with a bewildering variety of connections and functions. We present an intriguing case of intermittent vertical diplopia due to an artery of Percheron ischemic infarct of the bilateral paramedian thalami. We seize upon this opportunity to simplify the thalamic nuclei sub-divisions and their vascular supply. In this process, we outline the phenotypic variability of thalamic diplopia and ophthalmoplegia and their various underlying mechanisms.
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  • Article
    Filippov V, Kerttula J, Chamorovskii Y, Golant K, Okhotnikov OG.
    Opt Express. 2010 Jun 07;18(12):12499-512.
    The results of theoretical and experimental studies of active tapered double-clad fibers, intending the optimization of its imperative parameters--tapering ratio, longitudinal profile, core/cladding diameters ratio, are presented. Using a refined taper geometry we have demonstrated power scaling of a ytterbium fiber laser pumped by low-brightness, cost-effective laser diodes up to 750 W, with 80% efficiency.
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