Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional mutagenesis reduces splicing fidelity in mammalian cells

Abstract Splicing fidelity is essential to the maintenance of cellular functions and viability, and mutations or natural variations in pre-mRNA sequences and consequent alteration of splicing have been implicated in the etiology and progression of numerous diseases. The extent to which transcriptional errors or lesion-induced transcriptional mutagenesis (TM) influences splicing fidelity is not currently known. To investigate this, we employed site-specific DNA lesions on the transcribed strand of a minigene splicing reporter in normal mammalian cells. These were the common mutagenic lesions O6-methylguanine (O6-meG) and 8-oxoguanine (8-oxoG). The minigene splicing reporters were derived from lamin A (LMNA) and proteolipid protein 1 (PLP1), both with known links to human diseases that result from deregulated splicing. In cells with active DNA repair, 1–4% misincorporation occurred opposite the lesions, which increased to 20–40% when repair was compromised. Furthermore, our results reveal that TM at a splice site significantly reduces in vivo splicing fidelity, thereby changing the relative expression of alternative splicing forms in mammalian cells. These findings suggest that splicing defects caused by transcriptional errors can potentially lead to phenotypic cellular changes and increased susceptibility to the development of disease.
Microwave complex permeability of magnetite using non-demagnetising and demagnetising cavity modes

This paper investigates the use of a cylindrical microwave cavity resonator to measure the complex permeability of mixtures of magnetite (Fe3O4) and silicon dioxide (SiO2) using different field orientations. The weight percentages of the mixtures are varied and the effective bulk permeability is measured at frequencies from 3.8GHz to 10.16GHz using the TM110 and TE0np modes. The calculated permeability using the TM110 mode (where the sample experiences demagnetisation owing to the perpendicular field orientation) is verified using TE0np modes (where the sample demagnetisation is small). The TM110 measurement follows the permeability and loss trends with frequency, demonstrating the effectiveness of this non-invasive technique for measuring the broadband magnetic properties of powder mixtures at microwave frequencies.
The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome.

BACKGROUND Hepatopulmonary syndrome (HPS) is a chronic hepatic complication characterized by defect in arterial oxygenation induced by pulmonary vascular dilatation and vasoactive substances in the setting of chronic liver disease (CLD). This study is to investigate the abnormality of hemodynamic and vasoactive substances in hepatopulmonary syndrome. PATIENTS AND METHODS From September 2007 to September 2012, 58 patients with HPS in the General Surgery Department and Transplantation Center of Renji Hospital were enrolled for the case-control study. HPS patients enrolled were referred to as group H, CLD without HPS to as group C and case controls to as group N. Hemodynamic parameters of the systemic and pulmonary circulations as well as vasoactive substances in the radial and pulmonary arteries were measured in all patients. Univariate and multiple regression analysis were performed afterwards. RESULTS The mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and pulmonary vascular resistance (PVR) in HPS patients were significantly lower than those in CLD patients without HPS (p < 0.05). The nitrite-to-nitrate ratio (NO2-/NO3-), endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) in the radial and pulmonary arteries differed significantly among group H, group C and case controls (group N) separately (p < 0.05). The vasoactive intestinal peptide and 6-keto-prostaglandin-F1α in the radial and pulmonary arteries of group H were significantly higher than those in group N (p < 0.05). The NO2(-)/NO3(-) levels correlated negatively with PVR (r = -0.535, p < 0.05) and Endothelin-1 (r = -0.624, p < 0.05). CO (p < 0.05), CI (p < 0.05), SI (p < 0.05) and TNF-α (p < 0.05) level are considered significantly when performed with multiple regression analysis. CONCLUSIONS The CO increases and PVR decreases in HPS patients. The abnormally elevated NO2-/NO3- level in the pulmonary circulation leads to pulmonary vasodilation. ET-1 may induce nitric oxide synthesis and correlated negatively with PVR in HPS. CO, CI, SI and TNF-α level are independent risk factors for HPS patients' survival.
Middle cerebral artery peak systolic velocity in fetuses with homozygous alpha-thalassemia-1: case series.

OBJECTIVES The objective of this study is to evaluate the potential usefulness of middle cerebral artery peak systolic velocity (MCA-PSV) as a non-invasive means of detecting an anemic fetus from homozygous alpha-thalassemia-1. MATERIAL AND METHOD We observed four cases of referrals with complicated pregnancies in which the fetuses were suspected with homozygous alpha-thalassemia-1. Three out of four cases involved hydrop fetalis, detected through previous ultrasounds, while the remaining case was referred for prenatal diagnosis. Subsequently, we performed a detailed ultrasound and fetal MCA-PSV in all cases, and to confirm the diagnosis, we also performed cordocentesis. RESULTS With all the four cases having the gestational age range from 18 to 27 weeks, three showed hydrop fetalis. The remaining case, the 18-week gestational age fetus referred for prenatal diagnosis, showed an increase in the cardiothoracic ratio without other signs of hydrop fetalis. MCA-PSV suggested the presence of fetal anemia in all cases (with the velocity ranging from 37.3 to 62.2 cm/sec). The results obtained from cordocentesis confirmed fetal anemia and homozygous alpha-thalassemia-1 in all cases. CONCLUSION Peak systolic velocity of fetal middle cerebral artery can predict anemia in fetus affected with homozygous alpha-thalassemia-1 disease.
Air-sea exchange of nitrous oxide and methane in the Arabian Sea: A simple model of the seasonal variability

With a simple box model the seasonal variability of N₂O and CH₄ were simulated in surface layers in the central and western Arabian Sea. The model was able to reproduce the N₂O measurements except for times when cold water filaments occur (i.e., during the SW monsoon). Based on the comparison of model results and measurements, it is concluded that the saturation of N₂O in the surface layer of the Arabian Sea is mainly controlled by (i) the wind-driven air-sea exchange during the SW monsoon, (ii) entrainment of N₂O from the subsurface layer, and (iii) sea surface temperature variability. However, the contribution of the factors listed above to the seasonality of the N₂O saturations is different in the selected areas. The overall good agreement of model results and the majority of N₂O measurements suggest that N₂O formation in the surface layer of the Arabian Sea is negligible. The comparison of model’s results and CH₄ measurements revealed a more complex situation, partly due to considerable inconsistencies in the available CH₄ data. Thus, the situation for CH₄ remains unresolved and inconclusive.
Low RV from Circumstellar Dust around Supernovae

The effective extinction law for supernovae surrounded by circumstellar dust is examined with Monte Carlo simulations. Grains with light scattering properties as for interstellar dust in the Milky Way (MW) or the Large Magellanic Clouds (LMC), but surrounding the explosion site, would cause a semidiffusive propagation of light up to the edge of the dust shell. Multiple scattering of photons predominantly attenuates photons with shorter wavelengths, thus steepening the effective extinction law as compared to the case of single scattering in the interstellar medium. Our simulations yield typical values for the total-to-selective extinction ratio RV ∼ 1.5–2.5, as seen in recent studies of Type Ia supernova colors, with a steepening differential extinction toward shorter wavelengths.
Phosphorylation of Ribosomal Protein RPS6 Integrates Light Signals and Circadian Clock Signals

The translation of mRNA into protein is tightly regulated by the light environment as well as by the circadian clock. Although changes in translational efficiency have been well documented at the level of mRNA-ribosome loading, the underlying mechanisms are unclear. The reversible phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6) has been known for 40 years, but the biochemical significance of this event remains unclear to this day. Here, we confirm using a clock-deficient strain of Arabidopsis thaliana that RPS6 phosphorylation (RPS6-P) is controlled by the diel light-dark cycle with a peak during the day. Strikingly, when wild-type, clock-enabled, seedlings that have been entrained to a light-dark cycle are placed under free-running conditions, the circadian clock drives a cycle of RPS6-P with an opposite phase, peaking during the subjective night. We show that in wild-type seedlings under a light-dark cycle, the incoherent light and clock signals are integrated by the plant to cause an oscillation in RPS6-P with a reduced amplitude with a peak during the day. Sucrose can stimulate RPS6-P, as seen when sucrose in the medium masks the light response of etiolated seedlings. However, the diel cycles of RPS6-P are observed in the presence of 1% sucrose and in its absence. Sucrose at a high concentration of 3% appears to interfere with the robust integration of light and clock signals at the level of RPS6-P. Finally, we addressed whether RPS6-P occurs uniformly in polysomes, non-polysomal ribosomes and their subunits, and non-ribosomal protein. It is the polysomal RPS6 whose phosphorylation is most highly stimulated by light and repressed by darkness. These data exemplify a striking case of contrasting biochemical regulation between clock signals and light signals. Although the physiological significance of RPS6-P remains unknown, our data provide a mechanistic basis for the future understanding of this enigmatic event.
Psychosocial and demographic predictors of quality of life in a large sample of cancer patients

In recent years, there has been increasing emphasis on understanding how the cancer experience affects individuals' quality of life (QOL). The goal of this study was to assess the QOL and to identify psychosocial predictors of QOL among a large sample of patients with a variety of cancers. Specifically, we assessed the unique contribution of demographic variables, medical variables, and social support on patients' QOL and psychological adjustment. Three hundred and fifty‐one participants completed measures of social support, depression, anxiety, and QOL at their follow‐up medical visits. Analyses indicated that patients who were older and had better social support reported less anxiety (p<0.001), and patients who were older, married or who had more social support reported less depressive symptoms (p<0.01). Men, individuals whose cancer had not recurred, and those not undergoing active treatment reported better QOL in the physical health domain (p<0.05). Patients who were older, married, with more formal education, less advanced disease, and better social support reported better QOL in the mental health domain (p<0.05). Demographic variables (age, gender, marital status, education) were generally associated with measures of adjustment and QOL whereas medical variables (time since diagnosis, recurrence status, treatment variables, stage of disease) were not. Patients with more support reported less anxiety and depression and better QOL in the mental health domain, independent of demographic and medical variables. Assessing patients' level of social support may help to identify patients at risk for distress. Copyright © 2002 John Wiley & Sons, Ltd.
Gait Optimization in AIBO Robots Using an Estimation of Distribution Algorithm

In this paper we deal with the problem of automatically optimizing the gait of a robot for forward walking speed. Each different walking surface and/or the wear and tear of the robots determines the speed of the robot. This means that a specific gait for one surface may not be valid on another surface or even on the same surface some time later. Given a parametrized walk designed for the robot and one specific robot, we approach the problem of searching over the space of gaits for this robot by using an estimation of distribution algorithm and our knowledge of the problem, which allows us to considerably reduce the space of gaits over which the algorithm searches. We have implemented and tested our method using the Sony AIBO ERS-7 robot, significantly improving on our previous gait in a short period of training time.
Sedimentology and numerical modelling of aeolian sediment dispersal, McMurdo Sound, southwest Ross Sea, Antarctica

Large volumes of aeolian sand and dust are deflated from unconsolidated till deposits, and supraglacial debris surrounding McMurdo Sound, Antarctica. This material is transported offshore with windblown snow onto extensive winter-formed sea ice in the southwest Ross Sea, and is subsequently released into the water-column during summer sea ice breakup. Aeolian sediment samples were collected from a ~600 km² area of sea ice in western McMurdo Sound to determine the magnitude of deposition and identify sediment sources. A new 2-dimensional numerical aeolian sediment transport model (NaMASTE) tuned specifically for the McMurdo Sound area, was used to explore the ability of the local wind system to move sediment from source areas to sea ice and to determine the pattern and extent of aeolian sediment dispersal to the southwest Ross Sea. Debris deposits on the McMurdo Ice Shelf debris bands are the most dominant sediment source for the area. Unconsolidated deposits between Cape Bernacchi and Spike Cape, and the Taylor Valley mouth are significant secondary deposits. Mass accumulation rates varied between 0.15 g m⁻² y⁻¹ and 54.6 g m⁻² y⁻¹, equating to a background aeolian sediment accumulation rate, excluding extremely high values, of 1.14 ± 0.59 g m⁻² y⁻¹ for the McMurdo Sound coastal sea ice zone. This is 3–5 orders of magnitude more than global background dust fallout for the Ross Sea. Modal grain size is very-fine sand to coarse silt. Notably, much of this material is distributed in localised, high sand content plumes that are oriented downwind from source, with finer deposits found outside these zones. An average seafloor linear sedimentation rate of 0.2 cm ky⁻¹ is calculated for McMurdo Sound, which is minor compared to biogenic sedimentation for the region. This equates to ~0.7 Gg y⁻¹ aeolian sediment entering McMurdo Sound during sea ice melt. Application of NaMASTE successfully simulated the general aeolian sediment distribution pattern. Testing of model variables suggests that aeolian material is mainly transported during strong (>20 m s⁻¹) wind events. Modelling also suggests aeolian material from McMurdo Sound can be transported north to the Drygalski Ice Tongue, ~250 km from source, but only in very trace quantities.
ITCZ Splitting and the Influence of Large-Scale Eddy Fields on the Tropical Mean State

A spectral aqua-planet atmospheric general circulation model (AGCM) is forced with a series of zonally constant sea surface temperature (SST) distributions which are symmetric about the equator. For every oceanic forcing, the AGCM is run twice; a first time keeping all spectral modes and a second time with only the zonally symmetric ones. Parameterizations and boundary conditions remain the same in all cases thus allowing a consistent comparison of 3-D and 2-D flows. The comparative study shows that the structure of the tropical mean state of the full model is basically captured by the zonally symmetric model and that eddy fields merely modify this structure. This shows that the structure of the tropical mean state is mainly determined by the shape of the effective SST forcing. We confirm previous studies where the shape and strength of the Hadley circulation is comparable in the 3-D and 2-D experiments for cases with a well pronounced single ITCZ. So the underestimation of the Hadley circulation often found in idealized zonally symmetric models is not only due to the neglect of large-scale eddy fields. A new result is that both the full as well as the zonally symmetric model show the phenomenon of ITCZ splitting if the SST distribution gets flat enough at the equator. So ITCZ splitting can be explained by purely zonally symmetric mechanisms and is not necessarily induced by eddy fields. Eddies seem to stabilize single ITCZ circulation regimes. For SST distributions where ITCZ splitting occurs, multiple states exist in the zonally symmetric model. The atmosphere switches, for the same SST, between a single and double ITCZ state introducing a long-term variability in the tropics without the influence of mid-latitudes and without atmosphere-ocean
High Glucose Inhibits the Aspirin-Induced Activation of the Nitric Oxide/cGMP/cGMP-Dependent Protein Kinase Pathway and Does Not Affect the Aspirin-Induced Inhibition of Thromboxane Synthesis in Human Platelets

Since hyperglycemia is involved in the “aspirin resistance” occurring in diabetes, we aimed at evaluating whether high glucose interferes with the aspirin-induced inhibition of thromboxane synthesis and/or activation of the nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (PKG) pathway in platelets. For this purpose, in platelets from 60 healthy volunteers incubated for 60 min with 5–25 mmol/L d-glucose or iso-osmolar mannitol, we evaluated the influence of a 30-min incubation with lysine acetylsalicylate (L-ASA; 1–300 μmol/L) on 1) platelet function under shear stress; 2) aggregation induced by sodium arachidonate or ADP; 3) agonist-induced thromboxane production; and 4) NO production, cGMP synthesis, and PKG-induced vasodilator-stimulated phosphoprotein phosphorylation. Experiments were repeated in the presence of the antioxidant agent amifostine. We observed that platelet exposure to 25 mmol/L d-glucose, but not to iso-osmolar mannitol, 1) reduced the ability of L-ASA to inhibit platelet responses to agonists; 2) did not modify the L-ASA–induced inhibition of thromboxane synthesis; and 3) prevented the L-ASA–induced activation of the NO/cGMP/PKG pathway. Preincubation with amifostine reversed the high-glucose effects. Thus, high glucose acutely reduces the antiaggregating effect of aspirin, does not modify the aspirin-induced inhibition of thromboxane synthesis, and inhibits the aspirin-induced activation of the NO/cGMP/PKG pathway. These results identify a mechanism by which high glucose interferes with the aspirin action.
Bone Marrow Involvement in Patients With Nodular Lymphocyte Predominant Hodgkin Lymphoma

The significance of bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma is unknown. Of 275 patients diagnosed as lymphocyte predominant Hodgkin lymphoma at our institution (1983–2003), we identified 7 patients with purely nodular disease in the diagnostic lymph node biopsy specimen who also had bone marrow involvement. The latter was detected at the time of initial diagnosis in four patients, after one cycle of chemotherapy in one patient, and at relapse in two patients. There were six men and one woman with a median age of 37 years (range, 25–47 years). In all cases, the bone marrow was involved by large B cells, representing <10% of all cells, associated with a prominent T-cell and histiocytic background. All patients had laboratory, radiologic, and/or morphologic evidence of aggressive disease at the time of detection of bone marrow involvement. At last follow-up, four patients had died of their disease and three were alive following therapy. In conclusion, a small subset of patients in whom lymph node biopsy shows nodular lymphocyte predominant Hodgkin lymphoma with a purely nodular pattern also may have lymphoma in the bone marrow. Bone marrow involvement is associated with laboratory, radiologic, or morphologic evidence of aggressive disease and poor prognosis. Although the best terminology for these bone marrow lymphomas is uncertain, the aggressive clinical behavior of these neoplasms supports the need for intensive therapy.
Combining landscape approximation and local search in global optimization

Local search techniques have been applied in variant global optimization methods. The effect of local search to the function landscape can make multimodal problems easier to solve. For evolutionary algorithms, the usage of the step size control concept normally will result in failure by the individual to escape from the local optima during the final stage. We propose an algorithm combining landscape approximation and local search (LALS) which is designed to tackle those difficult multimodal problems. We demonstrate that LALS can solve problems with very rough landscapes and also that LALS has very good global reliability.
Evaluation of Long-Term Changes in Radiation, Cloudiness, and Surface Temperature on the Territory of the Former Soviet Union

Abstract Regular measurements of solar radiation carried out in the network of actinometric stations of the former Soviet Union (FSU) have shown a decreasing tendency in the time series of direct and global solar radiation during last decades. A statistically significant decrease has been found in 60% of the time series of global radiation annual totals obtained from 160 actinometric stations. Three large areas, where this decrease exceeded 2% per 10 years, were found (in the European part of the FSU, in West Siberia, and in the Far East). As the main reason for changes in solar radiation, increased cloudiness and atmospheric turbidity are considered. A more detailed analysis of long-term changes in radiation budget components obtained from two stations situated in rather different conditions (Moscow Meteorological Observatory in a large town and Toravere Actinometric Station in a rural area) allows us to point out the influence of a large town as a source of air pollution on the radiation transfer in the.
A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types

The vaginal microbiota is important in women’s reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an “intermediate” CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts.