Miracle-dz/UniFAR-FTUs huggingface dataset:
Macroautophagy and ERK phosphorylation counteract the anti-proliferative effect of proteasome inhibitor in gastric cancer cells

The ubiquitin-proteasome system and macroautophagy are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for the treatment of cancer. In this study, we show that proteasome inhibitor MG-132 suppressed gastric cancer cell proliferation and induced macroautophagy. The induction of macroautophagy was evidenced by the formation of LC3+ autophagosomes and the accumulation of acidic vesicular organelles and autolysosomes and was accompanied by the suppression of mammalian target of rapamycin complex 1 activity. Abolition of macroautophagy by knockdown of Class III phosphatidylinositol-3 kinase Vps34 or ATG5/7 sensitized gastric cancer cells to the anti-proliferative effect of MG-132 by promoting G2/M cell cycle arrest. In addition, MG-132 increased ERK phosphorylation whose inhibition by MEK inhibitor significantly enhanced the anti-proliferative effect of proteasome inhibition. To conclude, this study demonstrates that macroautophagy and ERK phosphorylation serve as protective mechanisms to counteract the anti-proliferative effect of proteasome inhibition. This discovery may have implications for the application of proteasome-directed therapy for the treatment of cancer.
Comparison of starch granule development and physicochemical properties of starches in wheat pericarp and endosperm.

BACKGROUND The objectives of this study were: (i) to characterize structural development of starch granule in pericarp and endosperm during wheat caryopsis growth; (ii) to compare physicochemical properties of starches in pericarp and endosperm; (iii) to further discover the relationships between pericarp starches and endosperm starches. Wheat pericarp and endosperm at different development stages were observed by light microscopy and scanning electron microscopy, respectively. Structural properties of starches were determined using X-ray power diffraction and (13) C solid nuclear magnetic resonance. RESULTS Pericarp starch granules (PSG) accumulated in amyloplasts and chloroplasts, and showed a typical accumulation peak at 5 days after fertilization (DAF), and then gradually decomposed during 5-22 DAF. PSG in the abdominal region showed a higher rate of decomposition compared to the dorsal region of pericarp. Endosperm starch granules (ESG) accumulated in amyloplasts, and occurred in endosperm cells at 5 DAF, then rapidly enriched the endosperm cells until 22 DAF. Compared with ESG, PSG were compound granules of irregular shape and small size distribution. The results also suggested lower amylose content and V-type single-helix content and higher proportions of double helices for PSG compared to ESG. CONCLUSION Based on the structural development of PSG and ESG, we speculated that the saccharides resulting from decomposition of PSG, on one hand, enabled the pericarp to survive before maturity of wheat caryopsis and, on the other hand, provided extra nutrition for the growth of ESG.
Health Insurance Costs and Employee Compensation: Evidence from the National Compensation Survey

This paper examines the relationship between rising health insurance costs and employee compensation. I estimate the extent to which total compensation decreases with a rise in health insurance costs and decompose these changes in compensation into adjustments in wages, non-health fringe benefits, and employee contributions to health insurance premiums. I examine this relationship using the National Compensation Survey, a panel dataset on compensation and health insurance for a sample of establishments across the USA. I find that total hourly compensation reduces by $0.52 for each dollar increase in health insurance costs. This reduction in total compensation is primarily in the form of higher employee premium contributions, and there is no evidence of a change in wages and non-health fringe benefits. These findings show that workers are absorbing at least part of the increase in health insurance costs through lower compensation and highlight the importance of examining total compensation, and not just wages, when examining the relationship between health insurance costs and employee compensation. Copyright © 2016 John Wiley & Sons, Ltd.
A newsvendor problem with boundedly rational strategic customers

This work considers a newsvendor system with strategic customers who are boundedly rational in terms of buying during the selling season or waiting for a discount in the savage market. The newsvendor’s decisions are to determine the selling price and order quantity. An optimisation problem is formulated with the incorporation of a game for interaction between strategic customers. We use the quantal choice framework to characterise the behaviour of strategic customers. It is shown that when the bounded rationality parameter is large, the quantal response equilibrium is unique; otherwise, multiple equilibria may exist. For the unique equilibrium case, it is not difficult to determine the optimal decisions for the newsvendor. For the multiple equilibria case, we give theoretical analyses and numerical calculations to provide implications to the newsvendor. Additionally, based on the special case (with perfectly rational strategic customers), some important results are also observed.
In Vivo Magnetic Resonance Imaging of Large Spontaneous Aortic Aneurysms in Old Apolipoprotein E-Deficient Mice

Abstract:Old ApoE-deficient mice were studied in vivo by magnetic resonance imaging (MRI) to prospectively evaluate vascular remodeling associated with atherosclerotic lesions. Material and Methods:Old female ApoE−/− mice on a normal diet were followed by MRI at 2 Tesla for a 3-month period and killed for histopathology. Aortic dimensions were measured and compared. Results:High-quality in vivo MR images were obtained at 2 Tesla with in plane spatial resolution of 86 × 86 &mgr;m2. On MRI, aortic lumen enlargement (>1.5-fold dilation) was seen in 10 of 13 mice, located predominantly in the suprarenal portion of the aorta. The mean maximal diameter of the aneurysms and of the aorta above and below the aneurysm were, respectively, 1.12±0.32 mm and 0.53±0.08 mm by MRI and 1.3±0.41 mm and 0.55±0.15 mm by histology. Matched histologic cross-sections of the aortic wall showed medial degradation with rupture of the internal elastic lamina at multiple sites, associated with fibrolipidic plaque containing cholesterol crystals. Conclusions:Aortic lumen enlargement was diagnosed in old ApoE−/− mice at sites with advanced atherosclerotic plaques. MRI has potential both as an in vivo imaging technique for screening mouse models for vascular wall pathology and to follow arterial remodeling associated with the disease progression.
Immediate Maternal and Neonatal Effects of Forceps and Vacuum-Assisted Deliveries

OBJECTIVE: To estimate the differences in immediate maternal and neonatal effects of forceps and vacuum-assisted deliveries. METHODS: We conducted a medical record review of all forceps and vacuum-assisted deliveries that occurred from January 1, 1998, to August 30, 1999, at Winthrop-University Hospital. Maternal demographics and delivery characteristics were recorded. Maternal outcomes, such as use of episiotomy and presence of lacerations, were studied. Neonatal outcomes evaluated were Apgar scores, neonatal intensive care unit admissions, cephalohematomas, instrument marks and bruising, and caput and molding. RESULTS: Of 508 operative vaginal deliveries, 200 were forceps and 308 were vacuum assisted. Forceps were used more often than vacuum for prolonged second stage of labor (P = .001). There was a higher rate of epidural (P = .02) and pudendal (P < .001) anesthesia, episiotomies (P = .01), maternal third- and fourth-degree perineal (P < .001) and vaginal lacerations (P = .004) with the use of forceps, whereas periurethral lacerations were more common in vacuum-assisted (P = .026) deliveries. More instrument marks and bruising (P < .001) were found in the neonates delivered by forceps, whereas there was a greater incidence of cephalohematomas (P = .03) and caput and molding (P < .001) in the neonates delivered with vacuum. Multivariable logistic regression analysis showed that forceps use was associated with an increase in major perineal and vaginal tears (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.27, 2.69; P = .001), an increase in instrument marks and bruising (OR 4.63; 95% CI 2.90, 7.41; P < .001) and a decrease in cephalohematomas (OR 0.49; 95% CI 0.29, 0.83; P = .007) compared with the vacuum. CONCLUSIONS: Maternal injuries are more common with the use of forceps. Neonates delivered with forceps have more facial injuries, whereas neonates delivered with vacuum have more cephalohematomas. LEVEL OF EVIDENCE: II-3
Synthesis and Structure-Activity Relationships of Fenbufen Amide Analogs

The previous discoveries of butyl fenbufen amide analogs with antitumor effects were further examined. The amide analogs with 1, 3, 4 and 8 carbons chains were prepared in 70–80% yield. Fenbufen had no cytotoxic effects at concentrations ranging from 10 to 100 μM. Methyl fenbufen amide had significant cytotoxic effects at a concentration of 100 μM. As the length of the alkyl amide side chain increased, the cytotoxic effects increased, and the octyl fenbufen amide had the greatest cytotoxic effect. After treatment with 30 μM octyl fenbufen amide, nearly seventy percent of the cells lost their viability. At the concentration of 10 μM, fenbufen amide analogs did not show cytotoxicity according to the MTT assay results. The NO scavenging activities of the fenbufen amide analogs were not significantly different from those of fenbufen.
Electronic Transport in Molecular Self-Assembled Monolayer Devices

A review on the mechanisms and characterization methods of electronic transport through self-assembled monolayers (SAMs) is presented. Using SAMs of alkanethiols in a nanometer-scale-device structure, tunneling is unambiguously demonstrated as the main intrinsic conduction mechanism for defect-free large bandgap SAMs, exhibiting well-known temperature and length dependencies. In-elastic electron tunneling spectroscopy exhibits clear vibrational modes of the molecules in the device, presenting direct evidence of the presence of molecules in the device.
(Mis)conceptions and reconceptioons about traditional science

“Traditional” science (ie, scientific work that has evolved from the natural sciences) is still said to rely on theory-neutral facts, quantitative data, and the search for universal laws. This depiction of science is incongruent with much contemporary thinking. This article examines three shifts in recent philosophy that are relevant for nursing science philosophy: the move from foundationalism to an understanding of the fallibility of science, the shift in emphasis from verification to justification of knowledge claims, and the recent examination of explanation by scientific realists. It is suggested that scientific realism may be a fruitful area of inquiry for philosophers of nursing science.
Diversity in mechanism and function of tRNA methyltransferases

tRNA molecules undergo extensive post-transcriptional processing to generate the mature functional tRNA species that are essential for translation in all organisms. These processing steps include the introduction of numerous specific chemical modifications to nucleotide bases and sugars; among these modifications, methylation reactions are by far the most abundant. The tRNA methyltransferases comprise a diverse enzyme superfamily, including members of multiple structural classes that appear to have arisen independently during evolution. Even among closely related family members, examples of unusual substrate specificity and chemistry have been observed. Here we review recent advances in tRNA methyltransferase mechanism and function with a particular emphasis on discoveries of alternative substrate specificities and chemistry associated with some methyltransferases. Although the molecular function for a specific tRNA methylation may not always be clear, mutations in tRNA methyltransferases have been increasingly associated with human disease. The impact of tRNA methylation on human biology is also discussed.
Small Interfering RNAs Mediate Sequence-Independent Gene Suppression and Induce Immune Activation by Signaling through Toll-Like Receptor 31

Small interfering (si) and short hairpin (sh) RNAs induce robust degradation of homologous mRNAs, making them a potent tool to achieve gene silencing in mammalian cells. Silencing by siRNAs is used widely because it is considered highly specific for the targeted gene, although a recent report suggests that siRNA also induce signaling through the type I IFN system. When human embryonic kidney 293 (HEK293) or keratinocyte (HaCaT) cell lines or human primary dendritic cells or macrophages were transfected with siRNA or shRNAs, suppression of nontargeted mRNA expression was detected. Additionally, siRNA and shRNA, independent of their sequences, initiated immune activation, including IFN-α and TNF-α production and increased HLA-DR expression, in transfected macrophages and dendritic cells. The siRNAs induced low, but significant, levels of IFN-β in HEK293 and HaCaT cells. Secretion of these cytokines increased tremendously when HEK293 cells overexpressed Toll-like receptor 3 (TLR3), and the increased secretion of IFN-β was inhibited by coexpression of an inhibitor of TIR domain-containing adapter-inducing IFN-β, the TLR3 adaptor protein linked to IFN regulatory factor 3 signaling. Although siRNA and shRNA knockdown of genes represents a new and powerful tool, it is not without nonspecific effects, which we demonstrate are mediated in part by signaling through TLR3.
A MODEL OF STRATEGIC APPROVAL VOTING IN A LARGE ELECTORATE

The article considers Approval Voting for a large population of voters. It is supposed that voters evaluate the relative likelihood of pairwise ties among candidates based on statistical information about candidate scores. This leads them to vote sincerely and according to a simple behavioral rule we call the 'Leader Rule'. At equilibrium, if a Condorcet-winner exists, this candidate is elected.
A new rate control scheme using quadratic rate distortion model

A new rate control scheme is used to calculate the target bit rate for each frame based on a quadratic formulation of the rate distortion function. The distortion measure are assumed to be either the average quantization scale of a frame or mean square error. The rate distortion function is modeled as a second order function of the inverse of the distortion measure. We presented a closed form solution for the target bit allocation which applies to both the digital storage media (DSM) applications (e.g., MPEG-2) and very low bit rate (VLBR) applications (e.g., MPEG-4). We perform experiments on a wavelet-based coder to demonstrate the versatility of our scheme. Model parameters are estimated using statistical linear regression analysis. Since the estimation uses the past encoded frames of the same picture prediction type (I, P and B pictures), the proposed approach is a single pass rate control technique. For the MPEG-2 coder the fluctuations of the bit counts are significantly reduced by 20 percent to 65 percent in the standard deviation of the bit count while the picture quality remains the same. For the MPEG-4 VM coder, the PSNR is improved by almost one dB as compared to the best MPEG-4 VM rate control using exhaustive combinations of quantization scale parameters.
Yeast 18S rRNA Dimethylase Dim1p: a Quality Control Mechanism in Ribosome Synthesis?

ABSTRACT One of the few rRNA modifications conserved between bacteria and eukaryotes is the base dimethylation present at the 3′ end of the small subunit rRNA. In the yeast Saccharomyces cerevisiae, this modification is carried out by Dim1p. We previously reported that genetic depletion of Dim1p not only blocked this modification but also strongly inhibited the pre-rRNA processing steps that lead to the synthesis of 18S rRNA. This prevented the formation of mature but unmodified 18S rRNA. The processing steps inhibited were nucleolar, and consistent with this, Dim1p was shown to localize mostly to this cellular compartment. dim1-2 was isolated from a library of conditionally lethal alleles of DIM1. In dim1-2strains, pre-rRNA processing was not affected at the permissive temperature for growth, but dimethylation was blocked, leading to strong accumulation of nondimethylated 18S rRNA. This demonstrates that the enzymatic function of Dim1p in dimethylation can be separated from its involvement in pre-rRNA processing. The growth rate ofdim1-2 strains was not affected, showing the dimethylation to be dispensable in vivo. Extracts of dim1-2 strains, however, were incompetent for translation in vitro. This suggests that dimethylation is required under the suboptimal in vitro conditions but only fine-tunes ribosomal function in vivo. Unexpectedly, when transcription of pre-rRNA was driven by a polymerase II PGKpromoter, its processing became insensitive to temperature-sensitive mutations in DIM1 or to depletion of Dim1p. This observation, which demonstrates that Dim1p is not directly required for pre-rRNA processing reactions, is consistent with the inhibition of pre-rRNA processing by an active repression system in the absence of Dim1p.
Improving the quality of care for Medicare patients with acute myocardial infarction: results from the Cooperative Cardiovascular Project.

CONTEXT Medicare has a legislative mandate for quality assurance, but the effectiveness of its population-based quality improvement programs has been difficult to establish. OBJECTIVE To improve the quality of care for Medicare patients with acute myocardial infarction. DESIGN Quality improvement project with baseline measurement, feedback, remeasurement, and comparison samples. SETTING All acute care hospitals in the United States. PATIENTS Preintervention and postintervention samples included all Medicare patients in Alabama, Connecticut, Iowa, and Wisconsin discharged with principal diagnoses of acute myocardial infarctions during 2 periods, June 1992 through December 1992 and August 1995 through November 1995. Indicator comparisons were made with a random sample of Medicare patients in the rest of the nation discharged with acute myocardial infarctions from August 1995 through November 1995. Mortality comparisons involved all Medicare patients nationwide with inpatient claims for acute myocardial infarctions during 2 periods, June 1992 through May 1993 and August 1995 through July 1996. INTERVENTION Data feedback by peer review organizations. MAIN OUTCOME MEASURES Quality indicators derived from clinical practice guidelines, length of stay, and mortality. RESULTS Performance on all quality indicators improved significantly in the 4 pilot states. Administration of aspirin during hospitalization in patients without contraindications improved from 84% to 90% (P< .001), and prescription of beta-blockers at discharge improved from 47% to 68% (P < .001). Mortality at 30 days decreased from 18.9% to 17.1% (P = .005) and at 1 year from 32.3% to 29.6% (P < .001). These improvements in quality occurred during a period when median length of stay decreased from 8 days to 6 days. Performance on all quality indicators except reperfusion was better in the pilot states than in the rest of the nation in 1995, and the differences were statistically significant for aspirin use at discharge (P < .001), beta-blocker use (P < .001), and smoking cessation counseling (P = .02). Postinfarction mortality was not significantly different between the pilot states and the rest of the nation during the baseline period, although it was slightly but significantly better in the pilot states during the follow-up period (absolute mortality difference at 1 year, 0.9%; P = .004). CONCLUSIONS The quality of care for Medicare patients with acute myocardial infarction has improved in the Cooperative Cardiovascular Project pilot states. Performance on the defined quality indicators appeared to be better in the pilot states than in the rest of the nation in 1995 and was associated with reduced mortality.
Exposures to lead

Abstract The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities.
Increased prevalence of severe malaria in HIV-infected adults in South Africa.

BACKGROUND Conflicting reports exist regarding the impact of human immunodeficiency virus (HIV) infection on the risk of severe malaria. We aimed to assess the effect of HIV infection status, advancing immunosuppression, and antimalarial immunity on the severity of malaria. METHODS A prospective cohort study was conducted. Consecutive hospitalized adult patients with falciparum malaria were tested for HIV antibodies and to determine CD4+ T cell count. Immunity to malaria was assessed by obtaining a history of childhood residence in an area where malaria is endemic. Patients were assessed for features of severe malaria. RESULTS Three hundred thirty-six patients were enrolled in the study, of whom 32 (10%) had severe malaria. The prevalence of HIV infection was 33%, and 111 patients (33%) were nonimmune to malaria. HIV-infected patients complained more frequently about respiratory and abdominal symptoms and less frequently about rigors and headache. Risk factors for severe malaria determined by multivariate analysis included being nonimmune to malaria, having a positive HIV serostatus, having an elevated parasite count, and having an increased white blood cell count. Risk of severe malaria was increased in HIV-infected patients with a CD4+ T cell count of < 200 x 10(6) cells/L (P < or = .001). Nonimmune HIV-infected patients were significantly more likely to have severe malaria (13 [36%] of 36 patients) than were nonimmune non-HIV-infected patients (9 [12%] of 75 patients; odds ratio, 4.15 [95% confidence interval, 1.57-10.97]; P = .003). HIV serostatus did not affect risk of severe malaria in the group from an area with endemicity (5 [7%] of 74 HIV-infected patients had severe malaria, and 5 [3%] of 151 non-HIV-infected patients had malaria; P = .248). CONCLUSIONS HIV-infected nonimmune adults are at increased risk of severe malaria. This risk is associated with a low CD4+ T cell count. This interaction is of great public health importance.