Miracle-dz/UniFAR-FTUs huggingface dataset:
p53-Dependent Chk1 Phosphorylation is Required for Maintenance of Prolonged G2 Arrest

Abstract Wang, X. Q. , Stanbridge, E. J., Lao, X. Y. , Cai, Q. , Fan, S. T. and Redpath, J. L. p53-Dependent Chk1 Phosphorylation is Required for Maintenance of Prolonged G2 Arrest. Radiat. Res. 168, 706–715 (2007). Targeting checkpoint kinases has been shown to have a potential chemosensitizing effect in cancer treatment. However, inhibitors of such kinases preferentially abrogate the DNA damage-induced G2 checkpoint in p53−/− as opposed to p53+/+ cells. The mechanisms by which p53 (TP53) can prevent abrogation of the G2 checkpoint are unclear. Using normal human diploid p53+/+ and p53−/− fibroblasts as model systems, we have compared the effects of three checkpoint inhibitors, caffeine, staurosporine and UCN-01, on γ-radiation-induced G2 arrest. The G2 arrest in p53+/+ cells was abrogated by caffeine, but not by staurosporine and UCN-01, whereas the G2 arrest in p53−/− cells was sensitive to all three inhibitors. Chk2 (CHEK1) phosphorylation was maintained in the presence of all three inhibitors in both p53+/+ and p53−/− cells. Chk1 phosphorylation was maintained only in the presence of staurosporine and UCN-01 in p53+/+ cells. In the presence of caffeine Chk1 phosphorylation was inhibited regardless of p53 status. The pathway of Chk1 phosphorylation → Cdc25A degradation → inhibition of cyclin B1/Cdk1 activity → G2 arrest is accordingly resistant to staurosporine and UCN-01 in p53+/+ cells. Moreover, sustained phosphorylation of Chk1 in the presence of staurosporine and UCN-01 is strongly related to phosphorylation of p53. The present study suggests the unique role of Chk1 in preventing abrogation of the G2 checkpoint in p53+/+ cells.
Essays in monetary and international economics

This dissertation is comprised of three essays in monetary and international macroeconomics. The first essay, titled “A Dynamic Model of Exogenous Exchange Rate Pass-Through”, examines a two-country open economy model with sticky prices where exporters’ choice of invoicing currency is endogenous. Besides generating incomplete pass-through, the model yields four main results. First, firms’ invoicing strategy is generally time-varying. Second, instant pass-through into import prices is greater than into export prices when depreciation is caused by a domestic monetary expansion. Thirdly, average pass-through is asymmetric in times of persistent depreciation and appreciation. It is higher under depreciation when the destination market is more competitive. Finally, cross-country differences in money supply variability produce an origin-based asymmetry: different average pass-through rates into import and export prices. The second essay, titled “Limited Commitment, Inaction and Optimal Monetary Policy”, examines the optimal frequency of monetary policy meetings when their schedule is pre-announced. The contribution of this paper is twofold. First, we show that in the standard New Keynesian framework infrequent but periodic revision of monetary policy may be desirable even when there are no explicit costs of policy adjustment. Adjustment of policy on a pre-announced schedule de facto acts as a commitment not to adjust in intermediate periods. We find that at short horizons ii gains from such commitment outweigh welfare costs of central bank’s inaction. Second, we solve for the optimal frequency of policy adjustment and characterize its determinants. When applied to the U.S. economy, our analysis suggests that the Federal Open Market Committee should revise the federal funds target rate no more than twice a year. Finally, the third essay, titled “Does the Federal Reserve Do What It Says It Expects to Do? ”, studies the behavior of the Federal Open Market Committee in setting the federal funds target rate and making a bias announcement. The bias announcement states the likely direction of policy at the next meeting. The current bias concerning the next interest rate decision should be the optimal forecast based on the committee’s interest rate policy rule. Therefore, the interest rate implied by the estimated policy should be consistent not only with the observed rate, but also with the observed bias announcement. We jointly estimate interest rate and bias announcement decision rules and find strong consistency between the two decisions in their response to inflation. However, the response to measures of economic activity is found inconsistent.
The genetic landscape of breast carcinomas with neuroendocrine differentiation

Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2‐negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2−) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER+/HER2− NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair. Their mutational repertoire was compared with that of ER+/HER2− breast carcinomas (n = 240), PAM50‐defined luminal breast carcinomas (luminal A, n = 209; luminal B, n = 111) and invasive lobular carcinomas (n = 127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1–11) somatic mutations, similar to that of luminal B breast carcinomas (median = 3, range 0–17) but significantly higher than that of luminal A breast carcinomas (median = 3, range 0–18, p = 0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, and ARID1A (3/18, 17%), and PIK3CA, AKT1, and CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2−, luminal A and invasive lobular carcinomas (p < 0.05), and showed a significantly higher frequency of somatic mutations affecting ARID1A (17% versus 2%, p < 0.05) and the transcription factor‐encoding genes FOXA1 (17% versus 2%, p = 0.01) and TBX3 (17% versus 3%, p < 0.05) than common‐type ER+/HER2− breast carcinomas. No TP53 somatic mutations were detected in NBCs. As compared with common forms of luminal breast carcinomas, NBCs show a distinctive repertoire of somatic mutations featuring lower frequencies of TP53 and PIK3CA mutations, enrichment for FOXA1 and TBX3 mutations, and, akin to neuroendocrine tumours from other sites, ARID1A mutations. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Crohn’s Disease Activity Index and Vienna Classification – Is It Worthwhile to Calculate before Surgery?

Background: Crohn’s disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The ‘Crohn’s disease activity index’ (CDAI) and the ‘Vienna classification’ (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. ‘strictureplasty’ in ‘stricturing disease’, ‘colon surgery’ in ‘colon involvement’), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 ‘surgical sites’ 425 ± 25 vs. 223.3 ± 25) and complications (357.1 ± 36.9 (with) vs. 244.4 ± 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications.
Calcium chloride concentration, injection time, and aging period effects on tenderness, sensory, and retail color attributes of loin steaks from mature cows.

Calcium chloride (CaCl2) injection effects on retail color changes and sensory traits of loin steaks from mature cows were studied. Left side strip loins (SL) of 10 carcasses were divided into three portions within . 5 h postmortem. One was a control, and the other portions were injected with either 150 mM or 200 mM CaCl2. At 24 h postmortem, the chilled, right side SL was removed and the same treatments applied. Steaks from each treatment were evaluated for color changes during 5 d of retail display. Treatments were also divided into 7-d or 14-d aging periods. Warner-Bratzler shear (WBS) values and sensory evaluations of juiciness, tenderness, flavor intensity, flavor description, and overall palatability were obtained on all treatments. Concentration of CaCl2 had no effect on measures of color. However, injection at 24 h reduced colorimeter L values and visual color scores on d 1 and 2 of retail display and increased discoloration scores on d 3 (P < .05) compared with injection at . 5 h. All steaks had greater than 40% discoloration when measured beyond d 3. Steaks aged 14 d exhibited significantly lower WBS values than steaks aged 7 d (P < .05). Injections of CaCl2 increased scores for juiciness, tenderness, and overall palatability, and aging improved tenderness, flavor intensity, flavor description, and overall palatability (P < .05). Cuts injected at 24 h had 8.3% and 8.8% higher yields than cuts injected at . 5 h or controls, respectively (P < .05). (ABSTRACT TRUNCATED AT 250 WORDS)
Towards Comprehensive Clinical Abbreviation Disambiguation Using Machine-Labeled Training Data

Abbreviation disambiguation in clinical texts is a problem handled well by fully supervised machine learning methods. Acquiring training data, however, is expensive and would be impractical for large numbers of abbreviations in specialized corpora. An alternative is a semi-supervised approach, in which training data are automatically generated by substituting long forms in natural text with their corresponding abbreviations. Most prior implementations of this method either focus on very few abbreviations or do not test on real-world data. We present a realistic use case by testing several semi-supervised classification algorithms on a large hand-annotated medical record of occurrences of 74 ambiguous abbreviations. Despite notable differences between training and test corpora, classifiers achieve up to 90% accuracy. Our tests demonstrate that semi-supervised abbreviation disambiguation is a viable and extensible option for medical NLP systems.
Replitase: Complete machinery for DNA synthesis

Replication of nuclear DNA in eukaryotes presents a tremendous challenge, not only due to the size and complexity of the genome, but also because of the time constraint imposed by a limited duration of S phase during which the entire genome has to be duplicated accurately and only once per cell division cycle. A challenge of this magnitude can only be met by the close coupling of DNA precursor synthesis to replication. Prokaryotic systems provide evidence for multienzyme and multiprotein complexes involved in DNA precursor synthesis and DNA replication. In addition, fractionation of nuclear proteins from proliferating mammalian cells shows co‐sedimentation of enzymes involved in DNA replication with those required for synthesis of deoxynucleoside triphosphates (dNTPs). Such complexes can be isolated only from cells that are in S phase, but not from cells in G0/G1 phases of cell cycle. The kinetics of deoxynucleotide metabolism supporting DNA replication in intact and permeabilized cells reveals close coupling and allosteric interaction between the enzymes of dNTP synthesis and DNA replication. These interactions contribute to channeling and compartmentation of deoxynucleotides in the microvicinity of DNA replication. A multienzyme and multiprotein megacomplex with these unique properties is called “replitase. ” In this article, we summarize some of the relevant evidence to date that supports the concept of replitase in mammalian cells, which originated from the observations in Dr. Pardee's laboratory. In addition, we show that androgen receptor (AR), which plays a critical role in proliferation and viability of prostate cancer cells, is associated with replitase, and that identification of constituents of replitase in androgen‐dependent versus androgen‐independent prostate cancer cells may provide insights into androgen‐regulated events that control proliferation of prostate cancer cells and potentially offer an effective strategy for the treatment of prostate cancer. J. Cell. Physiol. 209: 711–717, 2006. © 2006 Wiley‐Liss, Inc.
Advantages of focused helical computed tomographic scanning with rectal contrast only vs triple contrast in the diagnosis of clinically uncertain acute appendicitis: a prospective randomized study.

HYPOTHESIS Focused helical computed tomographic (CT) scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis. DESIGN Prospective randomized analysis of both CT scan modalities. INTERVENTIONS Only patients with uncertain diagnosis of acute appendicitis were entered in the study. The patients were then randomized to undergo the traditional triple-contrast CT scan or the new focused CT scan with rectal contrast only. Surgical management included operation or observation for 23 hours. RESULTS Ninety-one patients participated in the study, including 52 in the triple-contrast group and 39 in the rectal-contrast group. The demographics of the triple-contrast vs the rectal-contrast groups were similar. The triple-contrast group had a sensitivity of 97%, specificity of 86%, positive predictive value of 90%, and negative predictive value of 93%. The rectal-contrast group had a sensitivity of 88%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. There were 4 false-positive findings and 1 false-negative finding in the triple-contrast group compared with none in the rectal-contrast group. In the triple-contrast group, there were 13 perforated appendixes compared with 1 in the rectal-contrast group. The cost of a triple-contrast scan was 620 US dollars compared with 305 US dollars for a focused rectal-contrast scan. The negative appendectomy rate for the study was 8.0% (4 of 48 patients in the triple-contrast group vs 3 of 39 in the rectal-contrast group). CONCLUSIONS The demographics, sensitivity, specificity, and positive and negative predictive values were comparable in both groups. The focused rectal-contrast procedure was better tolerated by patients and demonstrated decreased morbidity, delay to diagnosis, perforation rate, and negative appendectomy rate with no missed diagnosis and decreased cost. Therefore, we believe that focused helical CT scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis.
MHC Class II Gene Silencing in Trophoblast Cells Is Caused by Inhibition of CIITA Expression

PROBLEM: Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)‐γ, a potent inducer of MHC class II genes. The suppression of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. The mechanism of this suppression is unknown.
Macro-Economic Factors in Credit Risk Calculations: Including Time-Varying Covariates in Mixture Cure Models

The prediction of the time of default in a credit risk setting via survival analysis needs to take a high censoring rate into account. This rate is because default does not occur for the majority of debtors. Mixture cure models allow the part of the loan population that is unsusceptible to default to be modeled, distinct from time of default for the susceptible population. In this article, we extend the mixture cure model to include time-varying covariates. We illustrate the method via simulations and by incorporating macro-economic factors as predictors for an actual bank dataset.
The role of inducible nitric oxide synthase and haem oxygenase 1 in growth and development of dental tissue'

In this study, the activity of the antioxidant enzyme network was assessed spectrophotometrically in samples of dental pulp and dental papilla taken from third‐molar gem extracts. The production of nitric oxide by the conversion of l‐(2,3,4,5)‐[3H] arginine to l‐(3H) citrulline, the activity of haem oxygenase 1 (HO‐1) through bilirubin synthesis and the expression of inducible nitric oxide synthase (iNOS), HO‐1 proteins and messenger RNA by Western blot and reverse‐transcribed polymerase chain reaction were also tested. The objective of this study was to evaluate the role of two proteins, iNOS and HO‐1, which are upregulated by a condition of oxidative stress present during dental tissue differentiation and development. This is fundamental for guaranteeing proper homeostasis favouring a physiological tissue growth. The results revealed an over‐expression of iNOS and HO‐1 in the papilla, compared with that in the pulp, mediated by the nuclear factor kappa B transcription factor activated by the reactive oxygen species that acts as scavengers for the superoxide radicals. HO‐1, a metabolically active enzyme in the papilla, but not in the pulp, seems to inhibit the iNOS enzyme by a crosstalk between the two proteins. We suggest that the probable mechanism through which this happens is the interaction of HO‐1 with haem, a cofactor dimer indispensible for iNOS, and the subsequent suppression of its metabolic activity. Copyright © 2011 John Wiley & Sons, Ltd.
Coinfections Acquired from Ixodes Ticks

SUMMARY The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in Ixodes ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among Ixodes ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected Ixodes ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of ≤28%. In North America and Europe, the majority of tick-borne coinfections occur among humans with diagnosed LD. Humans coinfected with LD and babesiosis appear to have more intense, prolonged symptoms than those with LD alone. Coinfected persons can also manifest diverse, influenza-like symptoms, and abnormal laboratory test results are frequently observed. Coinfecting pathogens might alter the efficiency of transmission, cause cooperative or competitive pathogen interactions, and alter disease severity among hosts. No prospective studies to assess the immunologic effects of coinfection among humans have been conducted, but animal models demonstrate that certain coinfections can modulate the immune response. Clinicians should consider the likelihood of coinfection when pursuing laboratory testing or selecting therapy for patients with tick-borne illness.
Electrophysiological characteristics of neurones in the guinea‐pig deep cerebellar nuclei in vitro.

The properties of neurones of the guinea‐pig deep cerebellar nuclei in a slice preparation were investigated by intracellular recording. The recorded population of cells did not differ morphologically from nuclear cells in vivo as judged from neurones stained with Lucifer Yellow. Fifty‐two out of sixty cells were spontaneously active with a regular firing pattern and a mean frequency of 26 +/‐ 14 (mean +/‐ S.D.) impulses/s. The action potentials lasted 0.41 +/‐ 0.07 ms (n = 60) with an amplitude of 58 +/‐ 8 mV. Input resistance was 44 +/‐ 10 M omega and the time constant of the membrane 13 +/‐ 3 ms. When stimulated with intracellularly injected depolarizing current pulses the cells responded with trains of action potentials. Near the threshold for the spike the stimulation produced firing of constant frequency and from more hyperpolarized levels an initial acceleration sometimes followed by a deceleration was seen. At levels less than 15 mV from the spike threshold there was a rebound train of spikes as a response to a hyperpolarizing current injection. At more hyperpolarized levels there was only a small depolarizing potential after the hyperpolarizing stimulation. Three types of subthreshold potentials were recorded. Spikelets rose from base line as 3‐10 mV depolarizing wavelets with a duration between 5 and 10 ms. They served as trigger potentials for the action potential. Plateau potentials were slow depolarizing potentials often reaching the spike threshold and thus generating long trains of action potentials. After‐hyperpolarizations followed each spike with a time course dependent on the previous activity of the cell. Plots of the firing frequency versus injected current were linear at the first and second interspike interval, after 50 ms of activity and at steady state. Plots of the voltage versus injected current were upward concave demonstrating anomalous rectification of the cell membrane. It is concluded that neurones in the deep cerebellar nuclei in vitro are spontaneously active because of the electroresponsive properties of their membranes. The physiological importance may be that the cerebellar output from these cells can be rapidly and efficiently modulated by synaptic potentials generated by Purkinje cells and mossy and climbing fibres.
High school and university students' knowledge and attitudes regarding biotechnology

Biotechnology has a considerable importance in Turkish biology curriculum. This study was designed to explore or indicate Turkish high school and university students' knowledge and attitudes toward biotechnology. A total number of 352 high school and 276 university students were invited to the study. The Biotechnology Knowledge Questionnaire (BKQ) with 16 items and Biotechnology Attitude Questionnaire (BAQ) with 37 items were used as data collection instruments. The statistically significant correlation was observed between the level of biotechnology knowledge and the subdimensions of attitudes toward biotechnology. We found no statistically significant difference between high school and university students' knowledge of biotechnology. In contrast, university students showed more positive attitudes toward biotechnology than did high school students. However, the effect of gender was equivocal; therefore, it did not support a “gender paradox” hypothesis. Our results suggest that although students' appreciation of (agricultural) biotechnology is relatively positive, the understanding of biotechnology processes is superficial and attitudes toward shopping genetically modified products are therefore negative. The possible impact of current science and biology curriculum, and also biotechnology news given in media on Turkish students' views of biotechnology is discussed.