Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical compositions of solid particles present in the Greenland NEEM ice core over the last 110,000 years

This study reports the chemical composition of particles present along Greenland's North Greenland Eemian Ice Drilling (NEEM) ice core, back to 110,000 years before present. Insoluble and soluble particles larger than 0.45 µm were extracted from the ice core by ice sublimation, and their chemical composition was analyzed using scanning electron microscope and energy dispersive X‐ray spectroscopy and micro‐Raman spectroscopy. We show that the dominant insoluble components are silicates, whereas NaCl, Na2SO4, CaSO4, and CaCO3 represent major soluble salts. For the first time, particles of CaMg(CO3)2 and Ca(NO3)2•4H2O are identified in a Greenland ice core. The chemical speciation of salts varies with past climatic conditions. Whereas the fraction of Na salts (NaCl + Na2SO4) exceeds that of Ca salts (CaSO4 + CaCO3) during the Holocene (0.6–11.7 kyr B.P.), the two fractions are similar during the Bølling‐Allerød period (12.9–14.6 kyr B.P.). During cold climate such as over the Younger Dryas (12.0–12.6 kyr B.P.) and the Last Glacial Maximum (15.0–26.9 kyr B.P.), the fraction of Ca salts exceeds that of Na salts, showing that the most abundant ion generally controls the salt budget in each period. High‐resolution analyses reveal changing particle compositions: those in Holocene ice show seasonal changes, and those in LGM ice show a difference between cloudy bands and clear layers, which again can be largely explained by the availability of ionic components in the atmospheric aerosol body of air masses reaching Greenland.
New treatments for metastatic melanoma

35% of patients after several weeks of treatment with EGFR inhibitors, and is likely to be attributable to EGFR-induced abnormal keratinocyte differentiation, which leads to impairment of the stratum corneum barrier and to aberrant sebaceous-gland function. Eczema craquelé is a reactive xerotic pattern of the stratum corneum characterized by reticular cracks and superficial fissures in a so-called crazy-paving pattern. Unusual extensive forms of eczema craquelé have been reported to be associated with endocrine disorders, nutritional deficiency, malignancy and drugs. The development of eczema craquelé in this patient 2 days after the cession of erlotinib is unusual. One possible explanation may be the subsequent use of cisplatin and pemetrexed. Cisplatin is reported to induce EGFR degradation and pemetrexed can reduce Akt phosphorylation downstream of the EGFR pathway. Both mechanisms might amplify the cytotoxicity of erlotinib and make the occult eczema overt. The short duration of eczema craquelé might be due to the short residual effect of erltotinib, which allowed normal epidermopoiesis to be re-established within 2 weeks despite subsequent courses of cisplatin and pemetrexed. The radiation-field sparing phenomenon after erlotinib treatment has been reported previously with follicular rash, but not eczema craquelé. Previous reports suggested that chronic radiation-induced changes, such as depletion of the basal layer of stem cells, absence of hair follicles and sebaceous glands, and presence of transforming growth factor-b-mediated fibrosis, as possible causes. Bossi et al. hypothesized that the drug does not reach the irradiated area because of impairment of the microvascular function and altered skin sensitivity to EGFR inhibitors resulting from skin changes secondary to radiotherapy. The complex interplay of radiotherapy, targeted therapy and chemotherapy in the development of adverse cutaneous reactions awaits further clarification. Our report suggests that a break of a few days after erlotinib therapy could be beneficial before starting pemetrexed– cisplatin.
MRCGP CSA: are the examiners biased, favouring their own by sex, ethnicity, and degree source?

BACKGROUND Concern exists regarding differential performance of candidates in postgraduate clinical assessments by ethnicity, sex, and country of primary qualification. Could examiner bias be responsible? AIM To explore whether candidate demographics affect examiners' judgements, by investigating candidates' case performances by candidates' and examiners' demographics. DESIGN AND SETTING Data on 4000 candidates (52,000 cases) sitting the MRCGP clinical skills assessment in 2011-2012. METHOD Univariate analyses were undertaken of subgroup performance (male/female, white/black and minority ethnic (BME), UK/non-UK graduates) by parallel examiner demographics. Due to confounding of variables, these were complemented by multivariate ANOVA and multiple regression analyses. RESULTS Univariate analysis showed some differences between outcomes between the same-group and other-group examiners: these were contradictory regarding examiners 'favouring their own', for example, males received higher marks from female examiners than from males: maximum effect size was 3.6%. A six-way ANOVA confirmed all three candidate and examiner variables as having significant effects individually, identifying one significant interaction (examiner sex by examiner ethnicity). Stepwise regression showed candidate variables predicting 12% of score variance, parallel examiner demographics adding little (approximately 0.2% of variance). One 'transactional' variable proved significant, explaining 0.06% of score variance. CONCLUSION Examiners show no general tendency to 'favour their own kind'. With confounding between variables, as far as the impact on candidates' case scores, substantial effects relate to candidate and not examiner characteristics. Candidate-examiner interaction effects were inconsistent in their direction and slight in their calculated impact.
Anti-atherogenic Antioxidants Regulate the Expression and Function of Proteasome α-Type Subunits in Human Endothelial Cells*

It has been proposed that phenolic antioxidants such as probucol exert their anti-atherogenic effects through scavenging lipid-derived radicals. In this study the potential for genomics to reveal unanticipated pharmacological properties of phenolic antioxidants is explored. It was found that two anti-atherogenic compounds, BO-653 and probucol, inhibited the expression of three α-type proteasome subunits, PMSA2, PMSA3, and PMSA4 in human umbilical vein endothelial cells. Here we report that both BO-653 and probucol caused not only inhibition of the mRNA levels of these three subunits but also inhibition of both the gene expression and protein synthesis of the α-type subunit, PMSA1. Other subunit components of the proteasome such as the β-type subunits (PMSB1, PMSB7), the ATPase subunit of 19 S (PMSC6), the non-ATPase subunit of 19 S (PMSD1), and PA28 (PMSE2) were not significantly affected by treatment with these compounds. The specific inhibition of α-type subunit expression in response to these antioxidants resulted in functional alterations of the proteasome with suppression of degradation of multiubiquitinated proteins and IκBα. These results suggest that certain compounds previously classified solely as antioxidants are able to exert potentially important modulatory effects on proteasome function.
Acetylation of Lysine 56 of Histone H3 Catalyzed by RTT109 and Regulated by ASF1 Is Required for Replisome Integrity*

In budding yeast, acetylation of histone H3 lysine 56 (H3-K56) is catalyzed by the Rtt109-Vps75 histone acetyltransferase (HAT) complex, with Rtt109 being the catalytic subunit, and histone chaperone Asf1 is required for this modification. Cells lacking Rtt109 are susceptible to perturbations in DNA replication. However, how Asf1 regulates acetylation of H3-K56 and how loss of H3-K56 acetylation affects DNA replication are unclear. We show that at low concentrations the Rtt109-Vps75 HAT complex acetylates H3-K56 in vitro when H3/H4 is complexed with Asf1, but not H3/H4 tetramers, recapitulating the in vivo requirement of Asf1 for H3-K56 acetylation using recombinant proteins. Moreover, the Rtt109-Vps75 complex interacts with Asf1-H3/H4 but not Asf1. In vivo, the Rtt109-Asf1 interaction is also dependent on the ability of Asf1 to bind H3/H4. Furthermore, the Rtt109 homolog in Schizosaccharomyces pombe (SpRtt109) also displayed an Asf1-dependent H3-K56 HAT activity in vitro. These results indicate that Asf1 regulates H3-K56 acetylation by presenting histones H3 and H4 to Rtt109-Vps575 for acetylation, and this mechanism is likely to be conserved. Finally, we have shown that cells lacking Rtt109 or expressing H3-K56 mutants exhibited significant reduction in the association of three proteins with stalled DNA replication forks and hyper-recombination of replication forks stalled at replication fork barriers of the ribosomal DNA locus compared with wild-type cells. Taken together, these studies provide novel insight into the role of Asf1 in the regulation of H3-K56 acetylation and the function of this modification in DNA replication.
Towards a calculator-aware number curriculum

While many current position papers and policy documents advocate a place for the use of calculators in elementary education, and point to their potential to enhance mathematical learning, there is continuing professional uncertainty over how to realise such aspirations. This paper reviews a pioneering effort to craft a 'calculator- aware' number curriculum. It examines pedagogical strategies based on Diagnose- Explain-Reinforce and Observe-Predict-Surpass sequences, and the wider use of calculators for purposes of Computation-Implementing, Result-Checking, Trial- Improving and Structure-Modelling. The paper then reports on research which examined the long-term impact of such a curriculum. It identifies the complexities of supporting pupils' development of personal methods of calculation, and of systematising such a curriculum to support progression in children's learning. The major long-term impact of the curriculum was on pupils' attitude to mental calculation and proficiency in it. Pupils proved more prone to calculate mentally, and more liable to adopt relatively powerful and efficient strategies. Analysis of pupils' calculator use in tackling a realistic number problem shows how effective use of the machine calls not only for mastery of operating procedures but a grasp of underlying mathematical ideas and the development of distinctive calculator methods. Finally, implications for policy and practice are suggested, emphasising that a calculator-aware approach cannot simply be improvised around a conventional curriculum.
Circularly Polarized Waveguide Antenna With Dual Pairs of Radiation Slots at Ka-Band

In this letter, a circularly polarized (CP) waveguide antenna with dual pairs of slots is presented for Ka-band applications. Circular polarization is realized by combining two orthogonal linear polarizations, which are generated by two pairs of radiation slots on a cavity surface, respectively. Two approaches of radiation slots, i.e., edge slots and corner slots, are discussed. The corner slots approach is employed to design a CP waveguide antenna at Ka-band. The measured axial ratio (AR) is below 3 dB from 29.69 to 30.06 GHz, or 1.2% relative bandwidth, with a minimal value of 0.4 dB at 29.9 GHz. The measured antenna gain is 9.8 dBi at 30 GHz, and the return loss is below –13 dB within the 3 dB AR bandwidth. The all-metal structure of the proposed antenna is very appropriate for tough environment applications.
An Unusual Cause of Intestinal Obstruction in a Young Adult Patient: Inflammatory Fibroid Polyp

Inflammatory fibroid polyps are uncommon benign lesions that originate in the submucosa of the gastrointestinal tract. The stomach and the ileum are the most commonly affected sites. Although inflammatory fibroid polyp is one of the rare conditions leading to intestinal obstruction in adults, it should be considered as a possible diagnosis in obstructive tumors of the small bowel causing intussusceptions. We present one case of inflammatory fibroid polyp as a rare cause of intussusception in a young adult patient.
Conscientiousness, Protective Behavioral Strategies, and Alcohol Use: Testing for Mediated Effects

The purpose of this study was to determine if use of protective behavioral strategies mediated the relationship between conscientiousness and alcohol use and alcohol-related problems. Participants were 186 college students at a state university campus in the Northeastern United States participating in a study examining the effectiveness of a brief alcohol intervention. Data were collected during the 2006–2007 academic years. Results indicated that use of protective behavioral strategies mediated the relationship between conscientiousness and both alcohol use and alcohol-related problems. Implications of the findings for researchers and clinicians in the area of preventing high-risk drinking among college students are discussed.
Significance of whole-pelvic radiotherapy for high-risk prostate cancer patients after radical prostatectomy.

Evaluation of: Spiotto MT, Hancock SL, King CR: Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients.Int. J. Radiat. Oncol. Biol. Phys.69, 54–61 (2007). Although most patients with localized prostate cancer are successfully treated with radical prostatectomy, high-risk patients often manifest biochemical and/or clinical relapse. Adjuvant or salvage radiotherapy is utilized for the treatment of these patients. For definitive radiotherapy for untreated prostate cancer, a randomized clinical study (radiation therapy oncology group [RTOG] 94–13), suggested superior effects of whole-pelvic radiotherapy to prostate-only radiotherapy. On the contrary, for adjuvant or salvage radiotherapy after radical prostatectomy, the role of whole-pelvic radiotherapy has not been extensively investigated. This retrospective study demonstrated better biochemical relapse-free survival in high-risk patients receiving adjuvant or salv.
Comparison of caloric reactivity between migraineurs and non-migraineurs

Abstract Objective: To demonstrate that the elevated prevalence of migraine in patients with vertigo disorders is due to enhanced sensitivity to dizziness, which could cause migraineurs to seek more, or earlier, medical care for vertigo disorders, confounding the ability to show causation. Methods: This case–control study investigated whether migraineurs perceive dizziness more intensely than non-migraineurs by comparing caloric responses in migraineurs, non-migraineurs and possible migraineurs. The summed caloric responses in the best responding ear were reviewed. Results: The migraine group had higher caloric response values, with a mean of 37.97 degrees per second, which was statistically significant when compared to the values for the possible migraine group (30.74 degrees per second (p < 0.05)) and the non-migraine group (30.70 degrees per second (p < 0.001)). Conclusion: The findings suggest that migraineurs experience vestibular stimuli more intensely compared to non-migraineurs, which might explain the association of migraine with vestibular disorders in general.
Baseline Estimates of Diarrhea-associated Mortality Among United States Children Before Rotavirus Vaccine Introduction

Objectives: Deaths due to diarrhea among US children declined substantially from the 1960s through the 1980s, but have not been recently assessed. We examined diarrhea-associated mortality among young US children from 1992 to 2006 to establish baseline estimates through which the effect of rotavirus vaccines, introduced in 2006, can be assessed. Methods: National Center for Health Statistics multiple cause-of-death mortality data were used to examine diarrhea-associated deaths and death rates among US children 1 to 59 months of age during 1992–2006. The winter residual method was used to indirectly estimate the annual number of diarrhea-associated deaths attributable to rotavirus. Results: An average of 369 diarrhea-associated deaths/year (3320 total deaths) occurred among US children 1 to 59 months of age during 1992–1998 and 2005–2006. The diarrhea-associated death rate increased 40% between the first 3 and last 2 years of the study period, from an average of 1.6 deaths per 100,000 to 2.3 deaths per 100,000. Black children died at almost 4 times the rate of white children. Diarrhea-associated deaths showed a winter seasonal pattern similar to that of rotavirus, particularly among children 4 to 23 months of age. Using indirect methods, we estimated 25 yearly rotavirus-associated deaths during the study period. Rotavirus vaccination could potentially prevent 21 of these deaths annually. Conclusions: Diarrhea-associated mortality among US children stabilized but appears to be increasing in recent years. Rotavirus was associated with a small but significant number of preventable deaths. The national multiple cause-of-death data should prove useful for assessing mortality impact of rotavirus vaccination in the United States.
A generic simulation model for planning critical care resource requirements

Intensive care capacity planning based on factual or forecasted mean admission numbers and mean length of stay without taking non‐linearity and variability into account is fraught with error. Simulation modelling may allow for a more accurate assessment of capacity needs. We developed a generic intensive care simulation model using data generated from anonymised patient records of all admissions to four different hospital intensive care units. The model was modified and calibrated stepwise to identify important parameters and their values to obtain a match between model predictions and actual data. The most important characteristic of the final model was the dependency of admission rate on actual occupancy. Occupancy, coverage and transfers of the final model were found to be within 2% of the actual data for all four simulated intensive care units. We have shown that this model could provide accurate decision support for planning critical care resource requirements.
Hemolytic and thrombocytopathic characteristics of extracorporeal membrane oxygenation systems at simulated flow rate for neonates*

Objective: A state-of-the-art centrifugal pump combined with hollow-fiber oxygenator for extracorporeal membrane oxygenation has potential advantages such as smaller priming volumes and decreased potential to cause tubing rupture as compared with the traditional roller head/silicone membrane systems. Adoption of these state-of-the-art systems has been slow in neonates as a result of past evidence of severe hemolysis that may lead to renal failure and increased mortality. Extracorporeal systems have also been linked to platelet dysfunction, a contributing factor toward intracranial hemorrhage, a leading cause of infant morbidity. Little data exist comparing the centrifugal systems with the roller systems in terms of hemolysis and platelet aggregation at low flow rates commonly used in neonatal extracorporeal membrane oxygenation. Design: Prospective, comparative laboratory study. Setting: University research laboratory. Subjects: Centrifugal pump, roller pump, hollow-fiber oxygenator, and silicone membrane oxygenator. Interventions: Comparative study using two pumps, the centrifugal Jostra Rotaflow (Maquet, Wayne, NJ) and the roller-head (Jostra, Maquet, Wayne, NJ), and two oxygenators, polymethlypentene Quadrox-D (Maquet) and silicone membrane (Medtronic, Minneapolis, MN). Five test runs of four circuit combinations were examined for hemolysis and platelet aggregation during 6 hrs of continuous use in a simulated in vitro extracorporeal membrane oxygenation circuit circulating whole swine blood at 300 mL/min. Measurements and Main Results: Hemolysis was assessed by spectrophometric measurement of plasma-free hemoglobin. Platelet aggregation was evaluated using monoclonal CD61 antibody fluorescent flow cytometry profiles. All of the extracorporeal membrane oxygenation systems created plasma-free hemoglobin at a similar rate compared with static blood control. There was no difference in the mean normalized index of hemolysis of the centrifugal/hollow-fiber oxygenator system as compared with the roller-head/silicone membrane systems (0.0032 g/100 L vs. 0.0058 g/100 L, p ≥ .7). None of the extracorporeal membrane oxygenation systems had a significant increase in platelet aggregation above baseline. Conclusions: In a low-flow neonatal environment, a state-of-the-art centrifugal pump combined with new fiber-type oxygenators appear to be safe in regard to hemolysis and platelet aggregation.
Characterization of Rain Microphysics based on Disdrometer and Polarimetric Radar Observations

Characterization of rain microphysics requires information on raindrop size distributions (DSDs). DSD measurements and retrievals, however, contain errors. In this paper, data from side-by-side disdrometer comparisons are presented to provide information that is not possible from single disdrometer measurements alone, allowing error effects to be quantified and a rain DSD model for radar retrieval to be improved. We also propose methods to mitigate sampling errors by filtering with sorting and averaging and by fitting to a Gamma DSD model with truncation and extrapolation. The Constrained- Gamma DSD model has thus been refined for the Southern Great Plains region of the United States.
Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment

Background BILB 1941 is a potent and specific non-nucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase in vitro. Methods In a double-blind sequential group comparison, 96 male HCV genotype 1 patients with minimal to mild liver fibrosis (Ishak or Metavir score 0–2) were randomized (8 to active treatment and 2 to placebo per dose group) and treated with 10–450 mg BILB 1941 every 8 h over 5 days. Viral load (VL) was measured using Roche Cobas TaqMan® assays. Results VL decreased by ≥1 log10 IU/ml in 2/8, 2/8, 1/8, 2/7, 0/8, 2/8 and 4/5 patients on 60, 80, 100, 150, 200, 300 and 450 mg, respectively. No response was seen with placebo. HCV subtype 1b showed better response than 1a, the effect of other covariables including prior interferon treatment was not significant. NS5B population sequencing and phenotyping identified baseline samples with reduced BILB 1941 susceptibility, but did not detect an on-treatment emergence of resistant mutants. Plasma drug levels were linear until 300 mg. No serious adverse events (AEs) were reported. AEs were mainly gastrointestinal-related (most frequent diarrhoea) and frequency increased with dose. On 450 mg, all five active-treated patients discontinued (four for gastrointestinal intolerance and one for increased aspartate aminotransferase and alanine aminotransferase levels) and the trial was discontinued. Conclusions BILB 1941 monotherapy demonstrated antiviral activity against HCV genotype 1, but gastrointestinal intolerance precluded testing of higher doses.
The Escherichia coli heat shock gene htpY: mutational analysis, cloning, sequencing, and transcriptional regulation

We have identified a new heat shock gene, designated htpY, located 700 bp upstream of the dnaK dnaJ operon. We cloned it and showed that it is transcribed clockwise vis-à-vis the Escherichia coli genetic map, in the same direction as the dnaK dnaJ operon. The htpY gene encodes a 21,193-Da polypeptide. Promoter mapping experiments and Northern (RNA) analysis showed that the htpY gene belongs to the classical heat shock gene family, because the transcription from its major promoter is under the positive control of the rpoH gene product (sigma 32) and resembles canonical E sigma 32-transcribed consensus promoter sequences. This conclusion has been strengthened by the construction and analysis of a phtpY-lacZ promoter fusion. Despite the fact that htpY null bacteria are viable, the expression of various E sigma 32 heat shock promoters is significantly decreased, suggesting that HtpY plays an important role in the regulation of the heat shock response. Consistent with this interpretation, overproduction of the HtpY protein results in a generalized increase of the heat shock response in E. coli.