Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of A2E in Prevention or Enhancement of Light Damage in Human Retinal Pigment Epithelial Cells¶

Abstract The process of sight (photostasis) produces, as a by-product, a chromophore called 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E), whose function in the eye has not been defined as yet. In youth and adulthood, A2E is removed from human retinal pigment epithelial (h-RPE) cells as it is made, and so it is present in very low concentrations, but with advanced age, it accumulates to concentrations reaching 20 μM. In the present study we have used photophysical techniques and in vitro cellular measurements to explore the role of A2E in h-RPE cells. We have found that A2E has both pro- and antioxidant properties. It generated singlet oxygen (Φso = 0.004) much less efficiently than its precursor trans-retinal (Φso = 0.24). It also quenched singlet oxygen at a rate (108 M−1 s−1) equivalent to two other endogenous quenchers of reactive oxygen species in the eye: α-tocopherol (vitamin E) and ascorbic acid (vitamin C). The endogenous singlet oxygen quencher lutein, whose quenching rate is two orders of magnitude greater than that of A2E, completely prevented light damage in vitro, suggesting that singlet oxygen does indeed play a role in light-induced damage to aged human retinas. We have used multiphoton confocal microscopy and the comet assay to measure the toxic, phototoxic and protective capacity of A2E in h-RPE cells. At 1–5 μM, A2E protected these cells from UV-induced breaks in DNA; at 20 μM, A2E no longer exerted this protective effect. These results imply that the role of A2E is not simple and may change over the course of a lifetime. A2E itself may play a protective role in the young eye but a toxic role in older eyes.
Melatonin attenuates the focal cerebral ischemic injury by inhibiting the dissociation of pBad from 14‐3‐3

Abstract: It has recently been reported that melatonin protects neuronal cells from damage by enhancing Akt activation, thus mediating antiapoptosis signals. However, there is little information regarding the effects of melatonin on the activation of genes further downstream in the Akt signaling pathway in ischemic brain injury. This study investigated whether melatonin modulates the antiapoptotic signal through Akt and its downstream targets, Bad and 14‐3‐3. Adult male rats were treated with melatonin (5 mg/kg) prior to middle cerebral artery occlusion (MCAO). Brains were collected at 24 hr after MCAO and infarct volumes were analyzed. Our results confirm that melatonin significantly reduces infarct volume and decreases the positive reaction of TUNEL staining in the cerebral cortex. Signal pathway activation was measured by phosphorylation of Akt at Ser473 and Bad at Ser136 using Western blot analysis. Melatonin prevented the injury‐induced decrease of pAkt and pBad levels. However, melatonin did not affect the expression of 14‐3‐3, which acts as an antiapoptotic factor through interaction with Bad. Immunoprecipitation analysis showed that the interaction between pBad and 14‐3‐3 increased in the presence of melatonin, compared to that of control animals. Our findings suggest that melatonin prevents cell death because of brain injury and that these protective effects are mediated through maintaining the interaction between pBad and 14‐3‐3, thus blocking activation of the apoptotic pathway.
Explaining Returns through Valuation

This article develops an analytically coherent yet parsimonious framework which explains market returns in terms of contemporaneous information. It anchors on the idea that valuation (static perspective) can be connected to the dynamics that explain returns, and vice versa. The framework requires two components. First, an explicit function that maps information to an estimate of value—a valuation heuristic. Second, the framework assumes that the difference between a firm’s actual value and value-per-heuristic follows an autoregressive stochastic process with a contraction parameter and no intercept. The contraction parameter can be estimated efficiently and nonparametrically. This modeling suffices to derive implied returns. Using scaled Earnings Per Share (``EPS'') forecasts as valuation heuristics, we empirically evaluate the framework’s validity and robustness. Its explanatory power compares favorably to that of traditional ordinary least squares (``OLS'') regressions, despite only requiring a single parameter. In a setting with pooled annual data, the implied and realized returns correlations range between 64% and 73%.
A recent perspective on alcohol, immunity, and host defense.

BACKGROUND Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system. METHODS Medline and PubMed databases were used to identify published reports with particular interest in the period of 2000-2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity. RESULTS This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed. CONCLUSION Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects.
Load Adaptive Gate Driving Method for High Efficiency Under Light-Load Conditions

In this paper, a new gate driving method to improve light-load efficiency is proposed for the power conversion system with a standby converter. The proposed method reduces the gate driving voltage of power MOSFETs and the operating voltage of controller ICs under light-load conditions by adjusting the auxiliary output voltage of the standby converter. Therefore, the gate driving loss on MOSFETs and the loss on controller ICs are significantly reduced without the degradation of performance in the main power stage. To confirm the validity of this paper, the dc/dc server power supply with an input of 48 V, an output of 12 V/60 A for the dc/dc stage, and an output of 5 V/3 A for the standby stage is experimented.
Energy efficiency improvement of mobile terminals exploiting opportunistic scheduling and upper layers' queuing dynamics

Energy efficient link adaptation can significantly increase energy efficiency on the uplink of cell users. However, `far' users, users that face unfavorable radio conditions on their uplink, have limited room for improvement with respect to link adaptation. This paper investigates extra ways of increasing energy efficiency for both `far' and `near' users, without sacrificing system performance, utilizing properties of the MAC and the upper layers of the network protocols stack and specifically queuing dynamics at the Session Layer. In contrast to common intuition, we show that under a dynamic setting of active flows energy efficiency, especially at high loads, is significantly increased under the Proportional Fair (PF) Scheduling. Moreover, we elaborate on extra transmission opportunities that are apparent due to different service completion times of near and far users, coming up with a simple priority opportunistic strategy that outperforms PF with regards to energy efficiency, without sacrificing throughput. In fact throughput of both far and near users is increased under practically relevant conditions when far users are significantly more than near users.
Horizontal Transfer of CS1 Pilin Genes of Enterotoxigenic Escherichia coli

ABSTRACT CS1 is one of a limited number of serologically distinct pili found in enterotoxigenic Escherichia coli (ETEC) strains associated with disease in people. The genes for the CS1 pilus are on a large plasmid, pCoo. We show that pCoo is not self-transmissible, although our sequence determination for part of pCoo shows regions almost identical to those in the conjugative drug resistance plasmid R64. When we introduced R64 into a strain containing pCoo, we found that pCoo was transferred to a recipient strain in mating. Most of the transconjugant pCoo plasmids result from recombination with R64, leading to acquisition of functional copies of all of the R64 transfer genes. Temporary coresidence of the drug resistance plasmid R64 with pCoo leads to a permanent change in pCoo so that it is now self-transmissible. We conclude that when R64-like plasmids are transmitted to an ETEC strain containing pCoo, their recombination may allow for spread of the pCoo plasmid to other enteric bacteria.
Non-cooperative Binding of the MAP-2 Microtubule-binding Region to Microtubules (*)

Microtubule-associated protein (MAP)-2 is a multidomain cytoskeletal protein that copurifies with brain microtubules (MTs) through repeated cycles of warm polymerization and cold disassembly. Recent equilibrium binding studies of high molecular weight MAP-2ab to taxol-stabilized MTs suggest that the interactions are highly cooperative, as indicated by sigmoidal binding curves, non-linear Scatchard plots, and an apparent all-or-none response in MAP binding in titration experiments (Wallis, K. T., Azhar, S., Rho, M. B., Lewis, S. A., Cowan, N. J., and Murphy, D. B.(1993) J. Biol. Chem. 268, 15158-15167). To learn more about the mechanism of MAP-2 binding to MTs, we investigated the binding properties of bacterially expressed MT-binding region (MTBR) of bovine brain MAP-2. Scatchard plots of the binding data showed no evidence of cooperativity, as reflected by the linear plots of t;ex2html_html_special_mark_amp;ngr;/[MTBR] versus t;ex2html_html_special_mark_amp;ngr;. The stoichiometry was 1-1.1 mol of MTBR/mol of tubulin dimer, and the dissociation constant for the MTBR was 1.1 μM. Bovine brain tau protein competitively inhibited MAP-2 binding, as evidenced by an increased K value for MTBR binding to MTs. Although the second repeat peptide m2 (VTSKCGSLKNIRHRPGGG) is thought to play a dominant role in MAP-2 binding to MTs, a MTBR mutant (with m2 replaced by the third octadecapeptide repeat m3) displays an K of 2.8 ± 0.1 μM and stoichiometry of 0.9 ± 0.05 mol of MTBR/mol of tubulin dimer. Another mutant with additional copies of the second repeat, designated by us as MTBR[mm2m], displayed noncooperative binding with a K of 0.53 ± 0.05 μM and a stoichiometry of 2.2 ± 0.2 mol of mutant MTBR/tubulin dimer. Equilibrium sedimentation experiments demonstrated that the wild-type MTBR is monomeric, whereas MTBR[mm2m] selfassociates to a stable dimer over the concentration range used in our MT binding studies. This finding indicates that only one of the two MT-binding sites on the dimer is probably linked to a microtubule at any given time.
Proteolytic DNA for mapping protein-DNA interactions.

We describe a technique to determine sites on proteins involved in protein-DNA interactions. DNA was synthesized via polymerase chain reaction (PCR) to produce four polynucleotide products with phosphorothioate nucleotides at the A, T, G, or C residues. Limited conjugation with the chemical protease FeBABE results in the surface of DNA being randomly labeled at the phosphorothioate sites with this protein-cleaving reagent. After formation of a protein-DNA complex, the proteolytic DNA can be activated to cleave the protein backbone at sites near the DNA. This technique was used to study the bacterial RNA polymerase/lacUV5 DNA open promoter complex, about which significant structural information is available. Cleavage sites on the two largest subunits of RNA polymerase, beta and beta', agree well with a recent model based on the crystal structure of the core enzyme alpha(2)betabeta' [Naryshkin, N. , Revyakin, A. , Kim, Y. , Mekler, V. , and Ebright, R. H. (2000) Cell 101, 601-611]. The cleavage site present on alpha supports previous studies regarding DNA binding regions of the alpha subunit. Cleavage sites identified throughout the sigma(70) subunit help to orient it with respect to the open promoter complex.
Effect of glucagon on peripheral utilization of glucose in man.

GLUCAGON (HGF) is known to produce hyperglycemia by stimulating hepatic glycogenolysis (1, 2, 3). However, the influence of this substance on utilization of glucose by peripheral cells has not been clearly defined (4, 5). De Duve (4) has referred to glucagon as a “powerful insulin antagonist,” and has stated that in this regard glucagon is at least as effective as epinephrine. Pincus and Rutman (5) have demonstrated that glucagon can prevent the fall in blood glucose concentration following administration of small doses of insulin. Yet, in order for this protective effect to occur, the animal studied must have been well fed, and the glucagon must be given by repeated injection or continuous infusion. Evidence from other sources (6, 7) also indicates that the hyperglycemic effect of infused glucagon is evanescent and that any effect glucagon might have on peripheral glucose utilization necessarily must be transient in nature as well.
Diagnostic Strategies for Heart Disease in Women: An Update on Imaging Techniques for Optimal Management

Significant progress has been made toward increasing awareness of the risks of heart disease in women and in the area of sex-specific cardiovascular research. Yet, coronary artery disease remains the leading cause of death of women in the western world. Over the last decade, the increased research focus of women at risk for ischemic heart disease has helped in defining and delineating some of the sex-specific factors, which have adversely affected the accuracy of imaging techniques in women. A focused body of clinical research has been published over the last few years, and there now exists a growing body of evidence on the diagnostic and prognostic accuracy of contemporary cardiovascular imaging techniques in women. Recent publications specifically addressing this issue [namely the 2005 American Heart Association Statement on Cardiac Imaging in Women, and the 2006 Women's Ischemia Syndrome Evaluation (WISE) study] are now changing the existing paradigm of ischemic heart disease from one representing a “man's disease,” to one including sex-specific algorithms. In this article we review the literature regarding the diagnostic and prognostic evaluation of coronary artery disease in women with respect to imaging.
LIN-41 inactivation leads to delayed centrosome elimination and abnormal chromosome behavior during female meiosis in Caenorhabditis elegans

An RNAi screen in the Caenorhabditis elegans gonad identifies new regulators for centrosome behavior in oogenesis. LIN-41 is found to be a promoter for centrosome elimination in oocytes. Moreover, LIN-41 depletion results in ectopic activation of centrosomes and abnormal chromosome behavior in female meiosis.
Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate

Duplexes of 21–23 nucleotide (nt) RNAs are the sequence‐specific mediators of RNA interference (RNAi) and post‐transcriptional gene silencing (PTGS). Synthetic, short interfering RNAs (siRNAs) were examined in Drosophila melanogaster embryo lysate for their requirements regarding length, structure, chemical composition and sequence in order to mediate efficient RNAi. Duplexes of 21 nt siRNAs with 2 nt 3′ overhangs were the most efficient triggers of sequence‐specific mRNA degradation. Substitution of one or both siRNA strands by 2′‐deoxy or 2′‐O‐methyl oligonucleotides abolished RNAi, although multiple 2′‐deoxynucleotide substitutions at the 3′ end of siRNAs were tolerated. The target recognition process is highly sequence specific, but not all positions of a siRNA contribute equally to target recognition; mismatches in the centre of the siRNA duplex prevent target RNA cleavage. The position of the cleavage site in the target RNA is defined by the 5′ end of the guide siRNA rather than its 3′ end. These results provide a rational basis for the design of siRNAs in future gene targeting experiments.
Neural correlates of “Theory of Mind” in very preterm born children

Very preterm (VPT) birth (<32 weeks’ gestational age) has been implicated in social‐cognitive deficits including Theory of Mind (ToM); the ability to attribute mental states to others and understand that those beliefs can differ from one's own or reality. The neural bases for ToM deficits in VPT born children have not been examined. We used magnetoencephalography (MEG) for its excellent spatial and temporal resolution to determine the neural underpinnings of ToM in 24 VPT and 24 full‐term born (FT) children (7–13 years). VPT children performed more poorly on neuropsychological measures of ToM but not inhibition. In the MEG task, both FT children and VPT children recruited regions involved in false belief processing such as the rIFG (VPT: 275–350 ms, FT: 250–375 ms) and left inferior temporal gyrus (VPT: 375–450 ms, FT: 325–375 ms) and right fusiform gyrus (VPT: 150–200 ms, FT: 175–250 ms). The rIPL (included in the temporal‐parietal junction) was recruited in FT children (475–575 ms) and the lTPJ in VPT children (500–575 ms). However, activations in all regions were reduced in the VPT compared to the FT group. We suggest that with increasing social‐cognitive demands such as varying the type of scenarios in the standardized measure of ToM, reduced activations in the rIFG and TPJ in the VPT group may reflect the decreased performance. With access to both spatial and temporal information, we discuss the role of domain general and specific regions of the ToM network in both groups. Hum Brain Mapp 38:5577–5589, 2017. © 2017 Wiley Periodicals, Inc.
Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance: a comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome.

BACKGROUND Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in donor-specific T cell frequencies also occurs after clinical lung transplantation and if such a decrease lowers the risk for bronchiolitis obliterans syndrome (BOS), a hallmark of chronic graft dysfunction. Therefore, we compared changes in posttransplant donor-specific cytotoxic T lymphocyte (CTLp) and helper T lymphocyte precursor (HTLp) frequencies in lung allograft recipients with good graft function and in recipients with BOS. METHODS Donor and third party specific CTLp and HTLp frequencies were determined by limiting dilution assay in pre- and posttransplant (1 year) peripheral blood samples of lung allograft recipients with good graft function (n = 13) and BOS (n = 10). RESULTS In recipients with good graft function, mean donor-specific CTLp frequencies decreased after transplantation (183 vs. 16 precursors before and after transplantation, respectively). Additionally, HTLp frequencies decreased but this was not specific for donor alloantigens because third party-specific HTLp frequencies decreased also. Surprisingly, recipients with BOS also showed a decrease in mean donor-specific CTLp frequencies after transplantation (332 vs. 49 precursors before and after transplantation, respectively). Again, HTLp frequencies decreased nonspecifically. CONCLUSIONS We conclude that donor-specific CTLp frequencies decrease after lung transplantation, but that this does not result in transplantation tolerance protecting the lung against the development of chronic graft dysfunction.
Low molecular weight of fluid in an alloy of EPDM/SIR [insulator applications]

Ethylene propylene diene rubber (EPDM), silicone rubber (SIR) and their alloys have good performance when used as outdoor insulators. The hydrophobicity of the surface is maintained in wet and polluted conditions as a result of the presence of silicone fluid on the surface. This is sustained by the diffusion of low molecular weight (LMW) fluid from the bulk to the surface. The amount of LMW fluid on the surface and in the bulk of the material determines the hydrophobicity during the lifetime of the alloy of EPDM/SIR used as insulators. A study of the amount, loss and generation of the LMW fluid in an alloy of EPDM/SIR used for outdoor insulators has been performed as a function of temperature in order to simulate the effects of the heat generated by the dry band arcing on the surface. From an infrared (IR) spectroscopy study, the LMW fluid extracted from the virgin specimen is found to be composed of two kinds of fluids, one comes from the EPDM and the other comes from the SIR components of the alloy. The component of the fluid from the SIR initially decreases with sequential heating at 200/spl deg/C for 32 h in air and extraction by immersion in hexane at 44/spl deg/C for 96 h, but then the component of the fluid from EPDM finally becomes predominant.
Improved fusion protein expression of EGFP via the mutation of both Kozak and the initial ATG codon

Since its discovery, green fluorescence protein (GFP) has been used as a reporter in a broad range of applications, including the determination of gene expresion in diverse organisms, and subcellular protein localization. pEGFP-N1 is a eukayotic expression vector encoding EGFP, the MCS of which locates at the N terminus of EGFP. In this study, the cDNA sequence of scorpion toxin BmKK2 was inserted into the XhoI-HindIII cut of pEGFP-N1 to construct a toxin-EGFP fusion gene (named pEGFP-BmKK2). Fluorescence imaging revealed that HEK 293T cells that were transfected by pEGFP-BmKK2 emitted green fluorescence. Transcription of pEGFP-BmKK2 was confirmed by RT-PCR. However, western blotting analysis showed that the transfected HEK 293T cells expressed mostly EGFP, but little toxin-EGFP fusion protein, implying that pEGFP-N1 cannot be used as a fusion expression vector for subcellular protein localization for the BmKK2 gene. Consequently, two modified recombinant vectors (pEGFP-BmKK2-M1 and pEGFP-BmKK2-M2) were constructed based on pEGFP-BmKK2. This greatly improved the expression of toxin-EGFP fusion protein from pEGFP-BmKK2-M2.