Miracle-dz/UniFAR-FTUs huggingface dataset:
Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location

von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age‐adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30‐kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Hum Mutat 23:40–46, 2004. © 2003 Wiley‐Liss, Inc.
‘Now without my car I don’t know what I’d do’: The transportation needs of older people in rural Lincolnshire

Britain is ageing. By 2035 the number of people aged 65 and over will account for 23% of the total population. This increase will have an impact on the economy, the provision of goods and services, and the resources needed to ensure a high quality of life into old age and active participation in society. The importance of transport in addressing social exclusion in rural communities has been acknowledged for some time and in this article we describe and report on the challenges faced by older people in rural Lincolnshire when trying to maintain active lifestyles. Drawing on a series of focus groups with older people (8–10 per group) who seldom accessed public or community transport, we examine the challenges faced by older people when trying to make journeys for social, leisure and health purposes. What becomes apparent is that, while community transport services play a vital role in rural communities, many older people are confused or unclear about what these services do, how they can be used, and how to access them. This article suggests that these services are often poorly publicised and underused in some areas of the county and therefore those most likely to benefit from them may be the ones least likely to use them.
Educational expansion, economic growth and antisocial behaviour: evidence from England

This paper investigates the impact of the increase in post‐compulsory schooling and economic growth on conviction rates for antisocial behaviour in England. I hypothesise that both educational and employment opportunities should lead to greater reductions in antisocial behaviour when they are combined than when they exist in isolation. I test this hypothesis empirically using three unique sources of area‐level data over time in England. Results show that expansion of post‐compulsory education is important for reductions in antisocial behaviour regardless of the additional impact of economic growth. Additionally, economic growth itself is found not to be associated with reductions in antisocial behaviour. Two possible explanations for these results are the diploma disease and the negative consequences of inequality.
Binomial Real Option Pricing for Restaurant Menu Analysis*

Numerous researchers have proposed methods to improve the profitability of restaurant menus. The profit-analysis techniques that have been proposed generally assess menu items according to popularity as against comparative contribution margin or a similar scheme that theoretically allows managers to apply a portfolio adjustment approach or simply to replace items that are low in profitability. However, none of the analytical models discussed in the literature consider the element of time, which is an essential consideration in planning for menu item replacement. This study uses a real option pricing model to construct time-axis profiles of menu items and to analyze their potential profitability given varying time constraints. The analysis applies a binomial real option pricing model, as applied to actual data, and a real option pricing model was used to compare the advantages and benefits of different menu items. A comparison of the binomial model’s results with those of other menu analysis models found that the time-based model was more effective in determining how to construct a menu portfolio.
Central Cities and Suburbs: Economic Rivals or Allies?

Theoretical models of urban development come to contradictory conclusions regarding the nature of central city-suburb interdependence. Unfortunately, empirical research into this relationship has been hampered by the lack of identifying information due to the endogeneity of factors affecting both central city and suburban growth. This paper resolves the identification problem by constructing an index that measures price shocks to export industries located in either center cities or their suburbs. The results indicate that positive export industry price shocks to one area have a positive spillover effect on the other. Interestingly, the cross-elasticity of suburban employment with respect to center city employment (1.18) significantly exceeds the cross-elasticity of central city employment with respect to suburban employment (0.24).
Independence and the State Auditor in Britain: A Constitutional Keystone or a Case of Reified Imagery?

The principles of state audit, in particular conceptions of independence, adhered to today in the major Westminster democracies originated in the British state audit reforms of the nineteenth century. State auditors prior to the nineteenth century were not expected to be independent of the executive. Instead, state audit was recognized as an executive function to be under the direct control of the executive. For a brief period in the mid-nineteenth century, parliament was able to take advantage of a succession of weak governments to redirect the loyalties of state audit from the executive to the legislature. Although parliament wanted to be served by a state auditor who would keep it informed of executive spending, it did not alter the dominance of the Treasury over state audit. The executive sought to sustain through a discourse of independence the perception that the controls exercised by the executive over the state auditor did not constitute either a threat to audit independence or result in capture of state audit by the executive. The discourse constructed the image of state audit as a function which was able to work unimpeded and independent of the executive despite a legislative framework which contained significant financial, procedural and staffing controls.
Köppen bioclimatic evaluation of CMIP historical climate simulations

Köppen bioclimatic classification relates generic vegetation types to characteristics of the interactive annual-cycles of continental temperature (T) and precipitation (P). In addition to predicting possible bioclimatic consequences of past or prospective climate change, a Köppen scheme can be used to pinpoint biases in model simulations of historical T and P. In this study a Köppen evaluation of Coupled Model Intercomparison Project (CMIP) simulations of historical climate is conducted for the period 1980–1999. Evaluation of an example CMIP5 model illustrates how errors in simulating Köppen vegetation types (relative to those derived from observational reference data) can be deconstructed and related to model-specific temperature and precipitation biases. Measures of CMIP model skill in simulating the reference Köppen vegetation types are also developed, allowing the bioclimatic performance of a CMIP5 simulation of T and P to be compared quantitatively with its CMIP3 antecedent. Although certain bioclimatic discrepancies persist across model generations, the CMIP5 models collectively display an improved rendering of historical T and P relative to their CMIP3 counterparts. In addition, the Köppen-based performance metrics are found to be quite insensitive to alternative choices of observational reference data or to differences in model horizontal resolution.
Buyer Power and Vertically Differentiated Retailers

We consider a model of vertical competition where retailers purchase an upstream input from a monopolist and are able to differentiate from each other in terms of quality. Our primary focus is to study the price, quality and welfare effects of introducing a large retailer, such as Costco or a Wal-Mart Supercenter, which is able to obtain lower wholesale prices (i.e., countervailing buyer power). We obtain two main results. First, the store with no buyer power (a “traditional retailer”) responds to the presence of the large retailer by increasing its quality, a finding that is consistent with recent efforts by traditional retailers to enhance consumers’ shopping experience. Second, the presence of a large retailer causes consumer welfare to increase through two different channels: a) the upstream discount obtained by the large retailer is partially passed on to the retail price, and b) a greater quality offered by the traditional retailer. Contrary to conventional wisdom, at low levels of countervailing power, most of the consumer welfare gains accrue to consumers with the highest willingness to pay for quality, due to the latter channel.
Glutathione S-transferases. The first enzymatic step in mercapturic acid formation.

Abstract The purification of homogeneous glutathione S-transferases B and C from rat liver is described. Kinetic and physical properties of these enzymes are compared with those of homogeneous transferases A and E. The letter designations for the transferases are based on the reverse order of elution from carboxymethylcellulose, the purification step in which the transferases are separated from each other. Transferase B was purified on the basis of its ability to conjugate iodomethane with glutathione, whereas transferase C was purified on the basis of conjugation with 1,2-dichloro-4-nitrobenzene. Although each of the four enzymes can be identified by its reactivity with specific substrates, all of the enzymes are active to differing degrees in the conjugation of glutathione with p-nitrobenzyl chloride. Assay conditions for a variety of substrates are included. All four glutathione transferases have a molecular weight of 45,000 and are dissociable into subunits of approximately 25,000 daltons. Despite the similar physical properties and overlapping substrate specificities of these enzymes, only transferases A and C are immunologically related.
Eau des villes : repenser des services en mutation. Introduction

Plan : LES SERVICES URBAINS DE L'EAU / LES GRANDS PPP : UN MODELE DE MOINS EN MOINS EXEMPLAIRE / AU-DELA DES MODELES INSTITUTIONNELS, REPENSER L'ARTICULATION VILLES - RESEAUX / UNE MODERNISATION DES SERVICES PUBLICS SOUS CONTRAINTE / LE FOISONNEMENT DES OFFRES NON CONVENTIONNELLES / CONCLUSION
The impracticality of an international “one size fits all” corporate governance code of best practice

Purpose - The purpose of this paper is to review corporate governance literature from an international perspective in terms of having a global code of corporate governance. Design/methodology/approach - Using a wide ranging literature review, the paper looks at the issue of a global corporate governance code of best practice from legal, corporate ownership structure and financial systems perspectives and the consequent/divergence issues that arise. Findings - The paper supports the hypothesis that the “one size fits all” approach to corporate governance, particularly the Anglo Saxon model, is not necessarily the right approach from a global perspective. Convergence on fundamental features of shareholder protection, independence of directors and establishment of committees may be the preferred way forward. Practical implications - The acceptance of a global corporate governance code is limited due to the adaptations in the business environment, investor confidence and corporate successes and failures. Originality/value - The analysis of the framework provides an interesting paper for corporate governance researchers.
Influence of typhoons on annual CO2 flux from a subtropical, humic lake

The Intergovernmental Panel on Climate Change predicts dramatic changes in precipitation patterns over the next century. One potential method for inferring how these changes in annual precipitation and intensity of storm events will influence aquatic ecosystems is to study and model present‐day lakes that share climatic characteristics with future climate scenarios. A small lake in north‐central Taiwan provided an excellent opportunity to explore the influence of intense meteorological events on CO2 exchange between surface waters and the atmosphere. Each year Yuan Yang Lake (YYL) is influenced by multiple typhoons that pass near the island of Taiwan. This lake has been instrumented with a sensor network that monitors water column and meteorological parameters at a high temporal resolution (2–10 min intervals). Using this high‐resolution data and manually collected CO2 samples, a mass‐balance model of CO2 dynamics in YYL was developed. In addition, a generalized simulation model was used to explore how typhoon frequency, intensity, and timing impact CO2 efflux to the atmosphere. Our findings suggest that increased annual precipitation and frequency of storm events results in greater epilimnetic interaction with the watershed and hypolimnion. These interactions resulted in elevated epilimetic CO2 concentrations and therefore greater evasion of CO2 to the atmosphere.
TOWARDS AN INSTITUTIONS-THEORETIC FRAMEWORK COMPARING SOLAR PHOTOVOLTAIC DIFFUSION PATTERNS IN JAPAN AND THE UNITED STATES

This paper studies and compares the actual historic solar photovoltaic (PV) installation data in Japan and the United States and proposes two deployment models to account for the differences. Deployment, along with research, development and demonstration, constitutes what is known as the RD3 (PCAST — President's Council of Advances in Science and Technology, United States) innovative chain of a new technology. Japan deploys PV focusing on the niche of utility grid-tied small-scale system (90 per cent of which is standardised roof-top residential PV system) using highly integrated value chain; this seems to draw upon her strong manufacturing culture and associated social technology and institutions for suppliers-dominated innovations.The United States deploys PV as a broadly defined innovation emphasising user-oriented customisation in both on and off grid, residential and industrial applications using small independent and intermediary system integrators. Empirical analysis of the diffusion patterns in the grid-tied small system category in respective contexts suggests that Japan's institutions seem to match her mass deployment strategy while the United States' combination of fragmented industry structure and diversity deployment gives rise to a complex diffusion pattern calling for continual institutional innovation or co-evolution. Our research, therefore, highlights that commercialisation of new technology or technical change, in general, is not an autonomous process and has strong institutional underpinnings. We formalise and generalise this "match" (Perez, 1983) argument in accordance with Nelson and Sampat's (2001) framework of physical technology vs social technology and their interactions. Some potential future extensions regarding utilities for this model are then highlighted.
Market Proxies as Factors in Linear Asset Pricing Models: Still Living with the Roll Critique

A new model misspecification measure for linear asset pricing models is proposed for the case where misspecification maps to latency of one of the pricing factors; in this case, the market return. This measure is suited both for testing models that include the market return as a pricing factor in a traditional sense (i.e., whether the chosen model does or does not price a collection of risky assets) and ranking those models (i.e., determining which model performs best). The proposed measure is used in pricing portfolios reflecting the size, value, and momentum premia. The conditional CAPM of Jagannathan and Wang (1996) is found to best the performance of both the simple CAPM and the ICAPM of Petkova (2006). Moreover, it is discovered that winner stocks in a momentum portfolio may have higher market betas than loser stocks.
Patents, Innovation and Growth

New growth theories emphasize the role played by innovation in promoting economic growth. Since it is difficult to quantify the amount of innovation undertaken in an economy, there is little available empirical evidence assessing the contribution made by innovation to growth, in contrast to abundant evidence on the role of physical capital accumulation in the growth process. In this paper patent data are used to proxy the amount of innovation undertaken in an economy. The patent data are used to explore two questions. First, how important is innovation to economic growth in Australia, and second, are reductions in innovations sourced in Australia offset by increases in foreign sourced innovations in Australia? Copyright 2000 by The Economic Society of Australia.
Cell wall and protoplast isoperoxidases in relation to injury, indoleacetic Acid, and ethylene effects.

In tobacco (Nicotiana Tabacum) pith, sweet potato (Ipomoea batatas), and carrot (Daucus carota) storage roots, differences were found between cell wall and protoplast peroxidases in their isoenzyme patterns, activity, and reaction to tissue injury.In the pith of elongating tobacco internodes, 90% of total activity was associated with the walls, 80% of which was due to the ionically and covalently bound fractions. With senescence, the increase in activity occurred mainly in the protoplast and the free fraction in the walls. The major protoplast isoperoxidases formed the free wall fraction, and the minor ones formed the wall bound fractions. The minor isoperoxidases were the only ones whose activities were affected by cut injury. Neither senescence nor injury caused qualitative changes in the cell isoperoxidase pattern. In the potato root cells, the isoperoxidases were also distinctive in their distribution and in their reactions to injury as well as to ethylene.In potato and carrot roots, the wall fractions contributed 30 and 95%, respectively, to total peroxidase activity. The injury-induced increase in peroxidase activity occurred mainly in the protoplast of tobacco pith and potato roots and almost entirely in the ionically bound fraction of the walls in carrot roots. Ethylene stimulated peroxidase development in potato roots, especially in the protoplast, but had no effect in either tobacco pith or carrot roots. Ethylene did not affect the inhibiting action of indoleacetic acid on peroxidase activity in tobacco pith, nor did indoleacetic acid significantly affect the stimulating action of ethylene in potato roots.Actinomycin D inhibited the injury-dependent development of peroxidase in tobacco pith, stimulated the injury- and ethylene-dependent peroxidase development in potato root, and had no effect on peroxidase development in carrot root. Cycloheximide prevented the increase in peroxidase activity in tobacco pith and potato root, but not in the carrot root. Thus, the enhancement of peroxidase activity resulted from either enzyme activation exclusively or from enzyme synthesis. RNA synthesis seems to be only indirectly related to isoperoxidase synthesis caused by injury or ethylene.
Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors

Purpose: This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors. Experimental Design: In a 3 + 3 dose escalation study, 10 patients received pembrolizumab 1, 3, or 10 mg/kg intravenously every 2 weeks until progression or intolerable toxicity. Seven additional patients received 10 mg/kg every 2 weeks. Thirteen patients participated in a 3-week intrapatient dose escalation (dose range, 0.005–10 mg/kg) followed by 2 or 10 mg/kg every 3 weeks. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: No dose-limiting toxicities were observed. Maximum administered dose was 10 mg/kg every 2 weeks. One patient with melanoma and one with Merkel cell carcinoma experienced complete responses of 57 and 56+ weeks' duration, respectively. Three patients with melanoma experienced partial responses. Fifteen patients with various malignancies experienced stable disease. One patient died of cryptococcal infection 92 days after pembrolizumab discontinuation, following prolonged corticosteroid use for grade 2 gastritis considered drug related. Pembrolizumab exhibited pharmacokinetic characteristics typical of humanized monoclonal antibodies. Maximum serum target engagement was reached with trough levels of doses greater than or equal to 1 mg/kg every 3 weeks. Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks. Conclusions: Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full potential for antitumor activity was 2 mg/kg every 3 weeks. Clin Cancer Res; 21(19); 4286–93. ©2015 AACR. See related commentary by van Elsas et al., p. 4251
The laboratory assessment of endurance performance in cyclists.

Performance in endurance activities depends on maximal aerobic capacity (VO2max) and the ability to sustain a high percentage of VO2max over time. This study examined whether noninvasive laboratory measures would be valid predictors of endurance performance in an individual-start bicycle race (TT). Eight experienced male cyclists (age = 25.1 +/- 3.3 years, weight = 75.0 +/- 5.7 kg, VO2max = 5.05 +/- 0.4 L.min-1) performed a progressive incremental exercise test to exhaustion on a cycle ergometer. VO2max, maximum power output, and ventilatory threshold were determined. Later the subjects completed a 40-km TT. Power output at the ventilatory threshold (VT watts) was correlated with race performance time and calculated power output during the competition (r = -0.81; r = 0.82). VT watts and VO2max accounted for 75% of the variance between subjects (r = 0.91) in performance time. These data indicate that simple laboratory measures can predict TT performance in trained cyclists. Individual differences may be accounted for by motivation, aerodynamic position, and efficiency.