Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1)

Classical nonhomologous DNA end-joining (C-NHEJ), which is a major DNA double-strand break (DSB) repair pathway in mammalian cells, plays a dominant role in joining DSBs during Ig heavy chain (IgH) class switch recombination (CSR) in activated B lymphocytes. However, in B cells deficient for one or more requisite C-NHEJ factors, such as DNA ligase 4 (Lig4) or XRCC4, end-joining during CSR occurs by a distinct alternative end-joining (A-EJ) pathway. A-EJ also has been implicated in joining DSBs found in oncogenic chromosomal translocations. DNA ligase 3 (Lig3) and its cofactor XRCC1 are widely considered to be requisite A-EJ factors, based on biochemical studies or extrachromosomal substrate end-joining studies. However, potential roles for these factors in A-EJ of endogenous chromosomal DSBs have not been tested. Here, we report that Xrcc1 inactivation via conditional gene-targeted deletion in WT or XRCC4-deficient primary B cells does not have an impact on either CSR or IgH/c-myc translocations in activated B lymphocytes. Indeed, homozygous deletion of Xrcc1 does not impair A-EJ of I-SceI–induced DSBs in XRCC4-deficient pro–B-cell lines. Correspondingly, substantial depletion of Lig3 in Lig4-deficient primary B cells or B-cell lines does not impair A-EJ of CSR-mediated DSBs or formation of IgH/c-myc translocations. Our findings firmly demonstrate that XRCC1 is not a requisite factor for A-EJ of chromosomal DSBs and raise the possibility that DNA ligase 1 (Lig1) may contribute more to A-EJ than previously considered.
New evidence for self‐medication in bonobos: Manniophyton fulvum leaf‐ and stemstrip‐swallowing from LuiKotale, Salonga National Park, DR Congo

The swallowing of entire leaves by apes across Africa without chewing has been observed for over 40 plant species. Here we add evidence for (a) a new site, LuiKotale where leaf‐swallowing of Manniophyton fulvum (Euphorbiaceae) is observed in bonobos, (b) a so far unreported ingestion of unchewed stemstrips of M. fulvum, we name stemstrip‐swallowing; and (c) a test of some of the requirements put forward by Huffman for the assessment of plants ingested for medical purpose. As ecological correlates we analyzed M. fulvum phenological data and examined 1,094 dung piles collected between 2002 and 2009. By that we assessed availability and choice of leaves. In addition, we provide the first full description of the behavior related to this plant species' use by chimpanzees or bonobos using 56 bouts of M. fulvum ingestion observed between October 2007 and February 2010. With these data we tested and met 4 of the 6 requirements given by Huffman, supporting ingestion of this species as self‐medication. Despite species' year‐round availability and abundance, M. fulvum was ingested only at specific times, in very small amounts, and by a small proportion of individuals per party. In the absence of our own parasitological data, we used M. fulvum swallowing as evidence for parasite infestation, and seasonality as a proxy for stressors underlying seasonal fluctuation and impacting immune responses. Using these indirect factors available, we investigated conditions for a parasite to develop to its infective stage as well as conditions for the host to cope with infections. Both rain and temperature were good predictors for M. fulvum ingestion. We discuss the use of M. fulvum with respect to its hispidity and subsequent purging properties and provide insight into its ethnomedicinal uses by humans, stimulating speculations about potentially additional pharmacological effects. Am. J. Primatol. 76:146–158, 2014. © 2013 Wiley Periodicals, Inc.
A TEST OF A GENERAL EQUILIBRIUM STOCK OPTION PRICING MODEL

An empirical version of the Cox, Ingersoll, and Ross (1985a) call option pricing model is derived, assuming execution price uncertainty in the options market. the pricing restrictions come in the form of moment conditions in the option pricing error. These can be estimated and tested using a version of the method of simulated moments (MSM). Simulation estimates, obtained by discretely approximating the risk-neutral processes of the underlying stock price and the interest rate, are substituted for analytically unknown call prices. the asymptotics and other aspects of the MSM estimator are discussed. the model is tested on transaction prices at 15-minute intervals. It substantially outperforms the Black-Scholes model. the empirical success of the Cox-Ingersoll-Ross model implies that the continuous-time interest rate implicit in synchronous transaction quotes of 90-day Treasury-bill futures contracts is an-albeit noisy-proxy for the instantaneous volatility on common stock. the process of the instantaneous volatility is found to be close to nonstationary. It is well approximated by a heteroskedastic unit-root process. With this approximation, the Cox-Ingersoll-Ross model only slightly overprices long-maturity options. Copyright 1993 Blackwell Publishers.
Single dose granulocyte colony-stimulating factor markedly enhances shear-dependent platelet function in humans

Granulocyte colony-stimulating factor (G-CSF) has been associated with the induction of a hypercoagulable state in patients as well as peripheral blood stem donors. Interestingly, sparse data exist on the kinetics of platelet and coagulation activation in response to G-CSF and it is unknown if G-CSF augments shear-dependent platelet function. These two issues are addressed in the current trial. Thirty-six healthy volunteers were enrolled into this study. All subjects received a single-dose of 5 µg/kg filgrastim intravenously. The effects of recombinant G-CSF on platelet and coagulation function were assessed by the platelet function analyzer PFA-100 (collagen/epinephrine (CEPI-CT), collagen/ADP (CADP-CT) closure times), von Willebrand factor activity (vWF : RiCO) ELISA, tissue factor (TF)-mRNA expression on circulating leukocytes and rotation thrombelastography (ROTEM). G-CSF time-dependently enhanced shear dependent platelet function measured by the PFA-100: CEPI-CT declined by 48% and CADP-CT by 31% with nadir values after 24 h (p < 0.001 as compared to baseline) and returned to near-baseline values after 72 hours. In accordance, VWF : RiCO increased by 59% after 24 h (p < 0.001) and returned to baseline 48 h later. TF-mRNA peaked after 4 hours (>6 fold increase p < 0.001) and reached near-baseline values after 24 hours. Nadir closure times were seen after 24 hours (−15%; p < 0.001). Single-dose administration of 5 µg/kg G-CSF significantly enhances shear-dependent platelet function and strongly induces leukocyte TF-mRNA, which translates into shortened clotting times ex vivo.
Building blocks for a new social architecture: the LEGO TM paradigm of an active society

English Social policy communities now often focus on ‘new social risks’. Despite a clear preference for controlling state spending, they also consider that these risks call for ‘social investments’. Concentration on investments, activation and the future is considered an optimal anchor for redesigning their welfare systems. Convergence around three ideas prompt us to speak of a shift towards a LEGOTM paradigm: learning over the life-course; a future orientation; and the collective benefits of an active society. Just as when Keynesianism was paradigmatic, however, we recognise that divergences exist in the ways that the paradigm is implemented.
Beam steering with nanoring reflectarray metasurfaces

One type of nanoring reflectarray metasurface is demonstrated to achieve high-efficiency beam steering in anomalous reflections. Rings with varied inner radius are designed to manipulate the phase front of the incident wave. The efficiency of anomalous reflections achieves more than 80% at the reflection angle of 53° under normal incidence. The light reflects along the surface of structure when the incident angle reaches to 12°. The anomalous reflection beams have the same polarization with the incoming light. This proposed structure can be applied in the high-efficiency waveplates, modulators, and couplers.
A DISCOURSE AND CONTENT ANALYSIS OF HOW NURSING IS FRAMED IN THE MAINSTREAM PRESS IN SOUTH AFRICA

4 Acknowledgements 6 List of figures 8 List of tables 8 List of abbreviations 9 Definitions 10 CHAPTER 1: INTRODUCTION 12 Overview 12 Theoretical framework 12 Literature review 14 Objectives 22 CHAPTER 2: METHODOLOGY 23 Study design 23 Study population 24 Sampling and sample size 25 Data collection and data sources 26 Data processing, analysis and management 26 Ethical considerations 29 CHAPTER 3: RESULTS 30 Quantitative results 30 Qualitative findings 53 CHAPTER 4: DISCUSSION 81
Assessment of Proliferative Activity in Colorectal Carcinomas by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)

The monoclonal antibody Ki-67 and the isospecific monoclonal antibody MIB-1 are routinely used in oncology to assess the proliferation index of tumor cells. A more objective and sensitive method is the determination of the of Ki-67 protein-specific mRNA by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In 25 resected colorectal adenocarcinomas of different stages and grades we determined between 0.2 and 4.4 amol (10−18 mol) Ki-67 protein-specific mRNA per microgram total RNA (median = 0.88 amol). The corresponding Ki-67 indices (expressing the percentage of Ki-67/MIB-1 positive tumor cells) ranged from 41 to 81% (median = 61%). We found a good correlation between Ki-67 index and mRNA expression (r = 0.75), a significant correlation between both data and tumor stage (primary tumor, regional nodes, metastasis [pTNM] staging classification) (p < 0.001), but not between both data and tumor grade. Both Ki-67 indices (p = 0.05) and mRNA levels (p = 0.014) correlated significantly to the patients' survival. These results demonstrate that the Ki-67 protein-specific quantitative RT-PCR is a useful method for the characterization of tumor cell proliferation.
Coronary MDCT and cardiac MR imaging: a revolution in radiology?

Despite all the progress made in diagnosis and treatment, cardiovascular diseases remain the main cause of death worldwide. The total cost of health care and lost productivity is estimated at $ 200 billion annually, making cardiovascular disease one of the most significant medical problems in our society. With recent advances in technology, cardiac multidetector row computed tomography (MDCT) and cardiac MR imaging (CMR) open up new avenues in diagnosis and are being increasingly utilized to manage patients with cardiovascular diseases. Cardiac imaging is a very interesting and rapidly growing field for radiologists who now consider this old specialty with renewed interest. However, because these new technologies offer a wider choice of examinations for the same patient, there is also the potential increase in cost to consider, so we must therefore be familiar with the technical advances and the recognized indications in order to ask for the appropriate examination. This paper will give a brief overview of technical skills involved in cardiac MDCT and CMR and a review of the clinical applications and indications of cardiac MDCT and CMR imaging in the assessment of coronary artery disease.
Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas.

BACKGROUND & AIMS Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways. METHODS Through a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of the p16-Rb and ATM-ATR DNA damage response pathways. We performed whole-exome sequencing of 20 unrelated subjects with multiple SSAs; most had features of serrated polyposis. We compared sequences with those from 4300 subjects matched for ethnicity (controls). We also used an integrative genomics approach to identify additional genes involved in senescence mechanisms. RESULTS We identified mutations in genes that regulate senescence (ATM, PIF1, TELO2,XAF1, and RBL1) in 5 of 20 subjects with multiple SSAs (odds ratio, 3.0; 95% confidence interval, 0.9–8.9; P =.04). In 2 subjects,we found nonsense mutations in RNF43, indicating that it is also associated with multiple serrated polyps (odds ratio, 460; 95% confidence interval, 23.1–16,384; P = 6.8 x 10(-5)). In knockdown experiments with pancreatic duct cells exposed to UV light, RNF43 appeared to function as a regulator of ATMATRDNA damage response. CONCLUSIONS We associated germline loss-of-function variants in genes that regulate senescence pathways with the development of multiple SSAs.We identified RNF43 as a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing SSAs.
Review Paper. Interest–rate term–structure pricing models: a review

The paper presents a review of interest–rate term structure modelling from the early short–rate–based models to the current developments. The emphasis of the paper is on the use of models for pricing complex derivatives or for relative–value option trading. Therefore, relative–pricing models are given a greater emphasis than equilibrium models. The paper argues that the current state of modelling owes a lot to how models have historically developed in the industry, and stresses the importance of ‘technological’ developments (such as faster computers or more efficient Monte Carlo techniques) in guiding the direction of theoretical research. In particular, the importance of the joint practices of vega hedging and daily model–recalibration is analysed in detail. The relevance of market incompleteness and of the possible informational inefficiency of derivatives markets for calibration and pricing is also discussed.
Are we inhibited? Renal insufficiency should not preclude the use of ACE inhibitors for patients with myocardial infarction and depressed left ventricular function.

CONTEXT Angiotensin-converting enzyme (ACE) inhibitors have been shown to decrease mortality in patients with myocardial infarction and depressed left ventricular function, but physicians may be reluctant to prescribe ACE inhibitors to patients with concomitant renal insufficiency. OBJECTIVE To evaluate whether patients with depressed left ventricular ejection fraction following acute myocardial infarction have a similar reduction in mortality from ACE inhibitors regardless of their renal function. DESIGN Retrospective cohort study using medical record data. SETTING All nonfederal acute care hospitals. PATIENTS A cohort of 20,902 Medicare beneficiaries aged 65 years and older directly admitted to the hospital from February 1, 1994, through July 30, 1995, and with a documented left ventricular ejection fraction of less than 40% measured by echocardiography, radionuclide scintigraphy, or angiography following a confirmed acute myocardial infarction. MAIN OUTCOME MEASURES One-year survival for patients who received or who did not receive an ACE inhibitor at hospital discharge, stratified by the patient's level of renal function. RESULTS For the entire cohort, the receipt of an ACE inhibitor on hospital discharge was associated with greater 1-year survival (hazards ratio, 0.84; 95% confidence interval, 0.77-0.91) after adjusting for patient demographic characteristics, comorbidity, severity of illness (including left ventricular ejection fraction), and the receipt of other therapies. In stratified models, the receipt of an ACE inhibitor was associated with a 37% (16%-52%) lower mortality for patients who had poor renal function (serum creatinine level,<265 micromol/L [<3 mg/dL]) and a 16% (8%-23%) lower mortality for patients who had better renal function. Use of aspirin therapy attenuated the benefit of ACE inhibitors in patients with poor renal function. CONCLUSIONS Moderate renal insufficiency should not be considered a contraindication to the use of ACE inhibitors in patients with depressed left ventricular ejection fraction following myocardial infarction. Use of aspirin therapy may attenuate the benefit of ACE inhibitors in patients with high serum creatinine levels; therefore, further studies are needed to determine whether treatment with aspirin, alternative antiplatelet agents, or anticoagulation is indicated for these patients.
Trait Anxiety and Tamoxifen Effects on Bone Mineral Density and Sex Hormone- Binding Globulin

Objective Tamoxifen therapy preserves BMD of the lumbar spine and increases levels of SHBG. We assessed whether trait anxiety, a factor linked with a reactive endocrine system, is associated with differential changes in BMD and SHBG levels in response to tamoxifen therapy. Methods Postmenopausal women (N = 140) with axillary-node-negative breast cancer participated in a 2-year randomized, double-blind, placebo-controlled trial of tamoxifen (10 mg twice a day). Levels of BMD and SHBG were assessed at baseline and at 3, 6, 12, 18, and 24 months. Results Trait anxiety predicted tamoxifen-induced changes in lumbar spine BMD; high levels of trait anxiety were associated with significantly greater lumbar spine BMD at 3, 12, and 24 months (p values < .05) for women on tamoxifen therapy. High anxiety also was associated with lower levels of SHBG for women using tamoxifen at 3, 12, 18, and 24 months (p values < .05). Conclusions Trait anxiety is associated with greater preservation of lumbar spine BMD in response to tamoxifen and with a suppression of tamoxifen-induced increases in SHBG. Trait anxiety and other affective traits may serve as indicators of underlying physiological processes that moderate the effects of estrogen receptor modulators (such as tamoxifen) in clinical trials. Such data may help to elucidate the physiological mechanisms responsible for some of the variation in individual responses to treatment.
Exploring Customer Experiential Components and the Conceptual Framework of Customer Experience, Customer Satisfaction, and Actual Behavior

This study explored the college student's on-campus foodservice experiential components and investigated the interrelationships among customer experience, customer satisfaction, and actual behavior. A sample of 566 respondents was collected at a large, public university in the southwestern United States. Findings showed respondent's customer experience positively influenced customer satisfaction and, subsequently, customer satisfaction positively influenced respondent's actual behavior. However, there was no direct effect of customer experience on actual behavior. The findings indicate that on-campus foodservice operators should pay additional attention to customer experience and customer satisfaction to increase customer visits. Limitations of the study and future research are also addressed.
Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase.

Immunoaffinity chromatography has been used to study the determinants of sterol efflux and net transport from cultured fibroblasts to human plasma medium. Sterol efflux was highly (approximately 80%) dependent upon a minor lipoprotein fraction containing apolipoprotein A-I unassociated with other apolipoproteins. The remaining activity was associated with the lipoprotein-free fraction of plasma and could be replaced by apoprotein-free albumin. Efflux was independent of lecithin:cholesterol acyltransferase (EC 2.3.1.43) activity. Net transport (i.e., the excess of efflux over influx) was completely inhibited by inhibition of lecithin:cholesterol acyltransferase or its removal by affinity chromatography on immobilized antibodies to apolipoprotein A-I or D (components of the transfer complex in human plasma). In uninhibited plasma, efflux and net transport rates had similar kinetics, suggesting that these were linked functions and that net transport was initiated by a carrier-dependent efflux step that, in the absence of lecithin:cholesterol acyltransferase activity, was associated with an equivalent influx of free sterol to the cells and that, in the presence of lecithin:cholesterol acyltransferase, was associated with esterification and transfer protein activity. The cholesterol carrier lipoprotein function (approximately 5% of plasma apolipoprotein A-I) appears to be the first step of lecithin:cholesterol acyltransferase-linked sterol transport from cells.
Evaluation of three-dimensional changes after sinus floor augmentation with different grafting materials.

OBJECTIVE The aim of this retrospective investigation was to assess the dimensional stability of different grafting materials after maxillary sinus floor augmentation with computed tomography (CT) scans. MATERIALS AND METHODS Two postoperative CT scans were available from 16 patients who had undergone maxillary sinus lift procedures. The first scan was made within a few days after the surgical intervention and the second one >6 months later. A total of 25 maxillary sinuses were augmented with different materials before implant insertion by lateral antrostomy in a staged approach. The volume of bone formation was calculated using the Somaris Sienet Magic View software. RESULTS Based on volumetric measurements of the augmented domes derived from the image sections, shrinkage was about 26%. The mean of the augmented bone volume was 3.02 cm(3) (1.4-5.56 cm(3); SD+/-1.18 cm(3)) as determined in the first CT scan. The respective mean volume in the second CT scan amounted to 2.28 cm(3) (0.92-4.46 cm(3); SD+/-1.07 cm(3)). CONCLUSION Within the limits of our descriptive and analytic study, the results indicate a significant reduction of the graft volume after maxillary sinus augmentation. Further prospective studies will have to evaluate the quantitative changes of different bone graft materials for maxillary sinus augmentation procedures in order to improve long-term implant stability.
Exchange rate variability as an OCA criterion: Are the candidates ripe for the euro?

One measure of whether the candidate countries in Central Europe should join the euro is the degree of real exchange rate variability they are experiencing at present. If it is high one could argue that they 'need' still some exchange rate flexibility to absorb asymmetric shocks. Our results suggest that the still remaining variability of real exchange rates in Central Europe might be mostly due to the fact that nominal exchange rates are still a source of shocks. The candidate countries have already now a lower degree of exchange rate variability (after taking into account the different degree of nominal variability) than the 'Club Med' countries during the early 1990. Moreover, the traditional OCA criteria, e.g. trade structure, do not seem to be related to real exchange rate variability. This reinforces the argument that there is little concrete evidence that the candidate countries would need to undergo a lengthy period of real convergence before they should join the euro.