Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of mutant BRAF splice variant signaling by next‐generation, selective RAF inhibitors

Vemurafenib and dabrafenib block MEK‐ERK1/2 signaling and cause tumor regression in the majority of advanced‐stage BRAFV600E melanoma patients; however, acquired resistance and paradoxical signaling have driven efforts for more potent and selective RAF inhibitors. Next‐generation RAF inhibitors, such as PLX7904 (PB04), effectively inhibit RAF signaling in BRAFV600E melanoma cells without paradoxical effects in wild‐type cells. Furthermore, PLX7904 blocks the growth of vemurafenib‐resistant BRAFV600E cells that express mutant NRAS. Acquired resistance to vemurafenib and dabrafenib is also frequently driven by expression of mutation BRAF splice variants; thus, we tested the effects of PLX7904 and its clinical analog, PLX8394 (PB03), in BRAFV600E splice variant‐mediated vemurafenib‐resistant cells. We show that paradox‐breaker RAF inhibitors potently block MEK‐ERK1/2 signaling, G1/S cell cycle events, survival and growth of vemurafenib/PLX4720‐resistant cells harboring distinct BRAFV600E splice variants. These data support the further investigation of paradox‐breaker RAF inhibitors as a second‐line treatment option for patients failing on vemurafenib or dabrafenib.
Beyond Opioid Patient-Controlled Analgesia: A Systematic Review of Analgesia After Major Spine Surgery

Abstract Postoperative pain control in patients undergoing spine surgery remains a challenge for the anesthesiologist. In addition to incisional pain, these patients experience pain arising from deeper tissues such as bones, ligaments, muscles, intervertebral disks, facet joints, and damaged nerve roots. The pain from these structures may be more severe and can lead to neural sensitization and release of mediators both peripherally and centrally. The problem is compounded by the fact that many of these patients are either opioid dependent or opioid tolerant, making them less responsive to the most commonly used therapy for postoperative pain (opioid-based intermittent or patient-controlled analgesia). The purpose of this review was to compare all published treatment options available that go beyond intravenous opiates and attempt to find the best possible treatment modality.
Asian Industrialization in Latin American Perspective: The Limits to Institutional Analysis

Kang, David C. Crony Capitalism: Corruption and Development in South Korea and the Philippines. Cambridge: Cambridge University Press, 2002. Figures, tables, notes, bibliography, index, 220 pp.; hardcover $60, paperback $27.99. Chibber, Vivek. Locked in Place: State-Building and Late Industrialization in India. Princeton: Princeton University Press, 2003. Figures, tables, abbreviations, notes, bibliography, index, 360 pp.; hardcover $49.50, paperback $22.95.
Bone mineral density in professional female dancers.

OBJECTIVES: To measure the long term effects of dance training and the contribution of the timing and duration of any menstrual disruption on bone mineral density (BMD). DESIGN: Measurement of BMD in 57 premenopausal, previously professionally dance trained women and the relationship to menstrual and training history. MAIN OUTCOME MEASURES: Bone density measurements at lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: The average Z score for BMD at the lumbar spine in the amenorrhoeic dancers was significantly below that for the normal population. The average Z score for BMD at the femoral neck in the eumenorrhoeic dancers was significantly above that for the normal population. There was a significant difference between the average Z score for BMD at both the lumbar spine and femoral neck between the amenorrhoeic and eumenorrhoeic dancers. Significant negative relationships were found between BMD at the lumbar spine and (1) age at menarche, (2) duration of amenorrhoea, (3) BMD at the femoral neck, and (4) the variable of ideal minus lowest weight, which was independent of amenorrhoea. No significant relationships were found between duration of oral contraceptive pill usage and BMD at either the lumbar spine or the femoral neck in eumenorrhoeic or amenorrhoeic dancers. In order to quantify the effect of a combination of these significant factors, a model of BMD was constructed using multiple regression incorporating the variables duration of amenorrhoea, age at menarche, and ideal minus lowest body weight. In this model R2 was 33.6%, in other words 33.6% of the total variation in the Z score for BMD at the lumbar spine could be accounted for by these factors. CONCLUSION: Professional female dancers with a history of delayed menarche and amenorrhoea have been identified as another group of premenopausal women potentially at risk of developing osteoporosis because of a decrease in BMD at the lumbar spine. The femoral neck in dancers with a history of amenorrhoea was partially protected from loss of BMD by virtue of being the major weight bearing site in previous dance training, and in eumenorrhoeic dancers BMD was significantly increased at this site.
Mucinous adenocarcinoma of the appendix in a hernia of Morgagni: a unique case report

Primary carcinoma of the appendix is a rare tumour, representing less than 0.5% of all gastrointestinal malignancies. A hernia of Morgagni is also a rare congenital anatomical abnormality. We report a unique case of a mucinous adenocarcinoma of the appendix contained within a hernia of Morgagni. To our knowledge, this is the first such case described. A previously well 50-year-old man presented to his general practitioner with 3 weeks of increasing constipation, abdominal discomfort and fatigue. Abdominal examination revealed hepatomegaly and a possible mass in the right upper quadrant. Computed tomography (CT) colonography identified a large right diaphragmatic hernia of Morgagni, occupying more than half of the right hemithorax. The right colon was contained within this hernia. A 19-mm caecal mass was identified. There were enlarged regional lymph nodes, and a small, indeterminate nodule in the right lung base. On questioning, the patient reported being made aware of a diaphragmatic hernia from a plain chest radiograph some years previously. Colonoscopy was not performed because of potential difficulty and adverse physiological effects with distension of the right colon in the chest cavity. Given this and the abnormality at the right lung base, positron emission tomography/CT was used to fully stage the patient. This demonstrated a fluorodeoxyglucose (FDG) avid lesion in the caecal pole (Fig. 1). There was no other evidence of FDG activity, including at the right lung base. CEA was normal at 2.1 ng/L. The patient came forward directly for right hemicolectomy and diaphragmatic hernia repair. A rooftop incision was performed. Excellent views were obtained of the diaphragm and hernia (Fig. 2). The hernia was reduced with gentle traction on the content. The adherent sac was then excised enbloc with the tumour. A standard right hemicolectomy was performed with a functional side-to-side stapled anastomosis. The diaphragmatic defect was repaired primarily with interrupted 0.0 Ethibond sutures. Post–operatively, the patient was managed on an enhanced recovery pathway and discharged on day 4. Histology revealed an appendiceal mucinous adenocarcinoma with a micrometastasis to one lymph node. Adjuvant chemotherapy was commenced 4 weeks post-operatively. Tumours of the appendix occur in 0.9–1.4% of appendicectomy specimens, and account for less than 0.5% of all gastrointestinal tract neoplasms. Tumours of this type are rarely diagnosed preoperatively. Mucinous adenocarcinomas account for 37–55% of all malignant appendiceal neoplasms. Fig. 1. Positron emission tomography computed tomography demonstrating an FDG-avid lesion in colon within hernia of Forgagni in right thorax.
THE NINTH DATA RELEASE OF THE SLOAN DIGITAL SKY SURVEY: FIRST SPECTROSCOPIC DATA FROM THE SDSS-III BARYON OSCILLATION SPECTROSCOPIC SURVEY

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z ∼ 0.52), 102,100 new quasar spectra (median z ∼ 2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with Teff < 5000 K and in metallicity estimates for stars with [Fe/H] > -0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SEGUE-2. The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the APOGEE along with another year of data from BOSS, followed by the final SDSS-III data release in 2014 December.
ID4 regulates mammary gland development by suppressing p38MAPK activity

The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.
Information Strategies and the Theory of the Firm

Information costs play a key role in determining the relative efficiency of alternative organisational structures. The choice of locations at which information is stored in a firm is an important determinant of its information costs. A specific example of information use is modelled in order to explore what factors determine whether information should be stored centrally or locally and if it should be replicated at different sites. This provides insights into why firms are structured hierarchically, with some decisions and tasks being performed centrally and others at different levels of decentralisation. The effects of new information technologies are also discussed. These can radically alter the patterns and levels of information costs within a firm and so can cause substantial changes in organisational structure
Agricultural policy in Russia and WTO accession

This article analyzes the implications of World Trade Organization (WTO) accession for Russian agricultural policy. Using Organisation for Economic Co-operation and Development (OECD) data on producer support from 2010, we identify two major characteristics of Russian agricultural and trade policy (a) reliance on sizeable differences between world and domestic prices to generate two-thirds of agricultural producer support and (b) highly distortionary budget support. We then consider whether the disciplines introduced by WTO accession will constrain or even roll back these distortionary policies, thereby substantially changing the nature of agricultural policies in Russia. Using data from OECD-FAO (Food and Agriculture Organization of the United Nations) and Russian Ministry of Agriculture projections, we conclude that the structure of OECD-type producer support in 2020 will be very similar to its current state. Market price support will continue to dominate the Producer Support Estimate, and the projected Current Total Aggregate Measure of Support (AMS) will approach the WTO Bound Total AMS (the ceiling on production-distorting support) only in 2018. For the reasons above, we conclude that although WTO accession provides opportunities for important changes in Russian sanitary, phytosanitary, food safety, trade, and tariff policies, membership is not a guarantee of systemic change. In fact, a serious look at Russian WTO commitments makes a minimum-change scenario quite possible and even likely.
Radioactive release from VVER-1000 reactors after a terror attack

One of the terror scenarios for nuclear power plants is a severe damage of the reactor containment caused by a plane crash or a missile. Owing to the loss of electric power the cooling of the core would not be maintained, leading to a core melt accident. Normally in the course of severe accidents an intact containment has the ability to retain a large part of the radioactive inventory. The goal of this work is the investigation of the behaviour of the radioactive releases from a VVER-1000 reactor during a severe accident with a large containment leak from the beginning of the accident. The results are compared with the release in a severe accident via a very small leakage due to the looseness of the containment.
Monetary Policy Transmission in Ghana: Does the Interest Rate Channel Work?

This paper analyzes interest rate pass-through in Ghana. Time series and bank-specific data are utilized to highlight linkages between policy, wholesale market, and retail market interest rates. Our analysis shows that responses to changes in the policy interest rate are gradual in the wholesale market. Prolonged deviation in the interbank interest rate from the prime rate illustrate the challenges the Bank of Ghana faces when targeting a short-term money market interest rate. Asymmetries in the wholesale market adjustment possibly relate to monetary policy signaling, weak policy credibility, and liquidity management. In the retail market, pass-through to deposit and lending interest rates is protracted and incomplete.1
The 3D reconstruction and visualization of Seokguram Grotto World Heritage Site

Seokguram Grotto is the most notable heritage site of the Shilla dynasty, representing the Buddhist rock art with various architectural, mathematical and geometrical skills. Owing to its universal value and a representative masterpiece of Buddhist culture around the world, it was listed as a World Heritage Site in December 1995 under the UNESCO World Heritage Criteria for Selection. Due to its enormous cultural significance and diverse location, the site witnesses various environmental conditions and tourism pressure which affects its prestigious status and sustainability. This raises the need of a 3D reconstruction and visualization, and presentation. 3D scanning approach is a generally accepted technique for the collection of 3D representation of heritage sites. For this reason, the laser scan technology was extensively used by measuring 3D surface coordinates to produce a complete 3D digital replica of Seokguram Grotto. Particularly, laser scanning technique was used to collect various 3D scan data, featuring high data acquisition rates, good accuracy and high 3D data density. The scan data were then optimized to produce geometric accuracy and visual quality of the collected textured 3D models. Our approach has enabled us to produce a complete 3D stereoscopic exhibition of Seokguram Grotto.
Genetic Engineering Applied to Agriculture: Opportunities and Concerns

Genetic engineering (also known as recombinant DNA technology) is the purposeful rearrangement of the genetic information of an organism. A little over a decade ago, scientists discovered that they could cut and tie together pieces of deoxyribonucleic acid (DNA) with certain enzymes. DNA contains the genetic code. Each gene is made up of DNA and codes for a specific protein. A chromosome is a linear array of tens of thousands of different genes. It is the combination of proteins that permit a cell to undergo the thousands of reactions (metabolism) required for life in the cell's specific environment. When a cell obtains the proper nutrients, it grows and doubles (makes a replica of itself). The new cell synthesizes the correct proteins through the code written in the individual genes, which are duplicated and transferred to the newly formed cell.
Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses.

OBJECTIVE To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS 6 healthy mature horses. PROCEDURES A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.
Asymmetric information content of the YTL/US$ exchange rate return: new evidence from the post-crisis data using arma-egarch-m modeling

In this paper, the volatility content of the YTL/US$ exchange rate return has been examined for the post-2001 crisis period till the early periods of 2008. Using exponential GARCH (EGARCH) methodology, estimation results indicate that volatility shocks on exchange rate return seem to be persistent so that the forecasts of the conditional variance converge to the steady state quite slowly. Besides, conditional variance of the exchange rate return reacts differently to equal magnitude negative and positive innovations. Plotting the News Impact Curve reveals that an unanticipated increase in exchange rate return would lead to more uncertainty when compared with the case of an unanticipated decrease.
Nasopharyngeal carcinoma: relationship between 18F-FDG PET-CT maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis and TNM classification

PurposeWe aimed to evaluate the relationships between primary tumour; maximum standardized uptake value (SUVmax), metabolic tumour volume (TV) and total lesion glycolysis (TLG) and tumour-node metastases (TNM) classification in nasopharyngeal carcinoma (NPC) patients. MethodsFluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography scans of 57 consecutive newly diagnosed NPC patients (age range, 15–80 years) were retrospectively reviewed. SUVmax, TV and TLG were recorded. Two-tailed Spearman's correlation was used to analyse the relationships between the metabolic parameters and the TNM staging system. ResultsPositive correlations were observed between SUVmax (P<0.001, R=0.516), TV (P<0.001, R=0.504) and TLG (P<0.001, R=0.620) and T-stage, and both TV and SUVmax were independent variables that significantly affected T-stage (P<0.001, adjusted R2=0.370). No other significant correlations were found between the metabolic parameters and TNM classification system. ConclusionThe metabolic parameters derived from fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography were positively correlated with T-stage in primary NPC. Our findings may suggest a complementary role of these parameters to TNM staging in prognostication of NPC patients.
Measuring Populism: Comparing Two Methods of Content Analysis

The measurement of populism – particularly over time and space – has received only scarce attention. In this research note two different ways to measure populism are compared: a classical content analysis and a computer-based content analysis. An analysis of political parties in the United Kingdom, the Netherlands, Germany and Italy demonstrates that both methods can be used to measure populism across countries and over time. Recommendations are presented on how to combine these methods in future comparative research on populism.
An importance performance analysis of performance dimensions in public hospitals

The purpose of this paper is to understand physicians’ perspectives on performance dimensions in public hospitals in the state of Kerala and to identify critical areas of concern. A survey was conducted in 23 district hospitals using an instrument developed on Likert’s scale. Responses were obtained on the perceived ‘importance’ and actual ‘performance’ of the identified dimensions. Importance performance analysis (IPA) conducted on the data brought into focus, several areas of functioning of public hospitals wherein, both managerial and policy interventions are required. Functioning of the intensive care unit (ICU), casualty, adequate beds, autonomy, uninterrupted supply chain and availability of funds were some of the governance issues that needed urgent remedial action. Redressing these issues will increase the motivation of physicians leading to better clinical outcomes. The findings argue well for major administrative and policy interventions. Further, this would strengthen the argument for more funds for health sector within the government.
Asset Price Based Estimates of Sterling Exchange Rate Risk Premia

In this paper we report estimates of the effective sterling, sterling/Deutsche mark and sterling/US dollar risk premia over a monthly 1987-2001 sample, generated using a conditional factor model for the stochastic discount factor of a representative 'worldwide' investor. The model relates this stochastic discount factor to the real return on a 'worldwide' stock portfolio, with the model parameters varying with variations in the slope of the 'world' term structure of interest rates. Econometric tests indicate that this model is accepted by the data. The corresponding parameter estimates are used to compute the risk premium for the three aforementioned sterling exchange rates. A graphical analysis indicates that, in terms of magnitude, our measure of the exchange rate risk premium is mainly of importance for the sterling/Deutsche mark exchange rate. Risk-adjusted test regressions for uncovered interest rate parity vis-`a-vis the major European currencies provide some confirmation for this.
INTRA DAY AND INTER MARKET VOLATILITY IN FOREIGN EXCHANGE RATES

Four foreign exchange spot rate series, recorded on an hourly basis for a six-month period in 1986 are examined. A seasonal GARCH model is developed to describe the time-dependent volatility apparent in the percentage nominal return of each currency. Hourly patterns in volatility are found to be remarkably similar across currencies and appear to be related to the opening and closing of the worlds major markets. Robust LM tests designed to deal with the extreme leptokurtosis in the data fails to uncover any evidence of misspecification or the presence of volatility spillover effects between the currencies or across markets.