Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cyclin-Dependent Kinase Inhibitor UCN-01 Plus Cisplatin in Advanced Solid Tumors: A California Cancer Consortium Phase I Pharmacokinetic and Molecular Correlative Trial

Background: UCN-01 (7-hydroxy-staurosporine) is a novel antineoplastic agent targeting cyclin-dependent kinases, which shows potent in vitro and in vivo activity against a broad range of tumor types. Our group has previously shown that UCN-01 potentiates the apoptotic response of agents such as cisplatin in vitro by preventing sequence-specific abrogation of G2 arrest caused by DNA-damaging chemotherapies. Patients and Methods: This National Cancer Institute–sponsored phase I trial was designed to determine the safety, maximum tolerated dose, and pharmacokinetics of escalating doses of cisplatin in combination with UCN-01 in patients with advanced malignant solid tumors, as well as to do molecular correlative studies on tumor specimens. Cisplatin was infused over 1 hour before UCN-01 (45 mg/m2/d) given as a 72-hour continuous infusion. Escalation of cisplatin was planned through five dose levels at 20, 30, 45, 60, and 75 mg/m2. Results: Ten patients were accrued. Accrual was halted at dose level 2 (cisplatin, 30 mg/m2) due to dose-limiting toxicities consisting of grade 5 sepsis with respiratory failure associated with grade 3 creatinine (one patient) and grade 3 atrial fibrillation (one patient). Plasma and salivary pharmacokinetics of UCN-01 were unaffected by cisplatin. Pretreatment and posttreatment tumor biopsies showed that UCN-01 was active against a key molecular target, the checkpoint kinase Chk1. Conclusions: This phase I trial failed to achieve targeted therapeutic dose levels of cisplatin when combined with prolonged infusion UCN-01. However, because preclinical data indicate that UCN-01 potentiates response to platinum, further studies with alternative dose schedules of the combination, or with other platinum analogues, are warranted.
The Strategy‐Performance Link in Product Innovation

The strategy a firm elects for its new product program is a critical element of the firm's corporate strategy. But little research has probed the performance results of firms' new product programs, and the strategy-performance link. This article reports the results of an empirical study of 122 firms, whose purpose was to identify the levels of new product performance achieved, and the strategies leading to different types of performance. Eight different performance gauges yielded three independent dimensions of new product performance. A total of five different types or clusters of “performers” were identified. And the strategies and characteristics that the “top performers” shared are described.
The High-Frequency Response of Exchange Rates and Interest Rates to Macroeconomic Announcements

Many recent papers have studied movements in stock, bond, and currency prices over short windows of time around macro announcements. This paper adds to the announcement effects literature in two ways. First, we study the joint announcement effects across a broad range of assets--exchange rates and U.S. and foreign term structures. In order to evaluate whether the joint effects can be reconciled with conventional theory, we interpret the joint movements in light of uncovered interest rate parity or changes in risk premia. For several real macro announcements, we find that a stronger than expected release appreciates the dollar today, but that it must either (i) lower the relative risk premium for holding foreign currency rather than dollars, or (ii) imply considerable future expected dollar depreciation. The latter implies an overshooting behavior akin to that described by Dornbusch (1976). Second, we use a longer span of high frequency data than has been common in announcement work. A longer span of high frequency data contributes to the precision of our estimates and allows us to explore the possibility that the effects of macro surprises on asset prices have varied over time. We find evidence, for example, that PPI releases had a larger effect on U.S. interest rates before about 1992 than subsequently.
A Comprehensive Review of Optical Stretcher for Cell Mechanical Characterization at Single-Cell Level

This paper presents a comprehensive review of the development of the optical stretcher, a powerful optofluidic device for single cell mechanical study by using optical force induced cell stretching. The different techniques and the different materials for the fabrication of the optical stretcher are first summarized. A short description of the optical-stretching mechanism is then given, highlighting the optical force calculation and the cell optical deformability characterization. Subsequently, the implementations of the optical stretcher in various cell-mechanics studies are shown on different types of cells. Afterwards, two new advancements on optical stretcher applications are also introduced: the active cell sorting based on cell mechanical characterization and the temperature effect on cell stretching measurement from laser-induced heating. Two examples of new functionalities developed with the optical stretcher are also included. Finally, the current major limitation and the future development possibilities are discussed.
Optimizing peptide matrices for identifying T‐cell antigens

Mapping T‐cell epitopes for a pathogen or vaccine requires a complex method for screening hundreds to thousands of peptides with a limited amount of donor sample. We describe an optimized deconvolution process by which peptides are pooled in a matrix format to minimize the number of tests required to identify peptide epitopes. Four peptide pool matrices were constructed to deconvolute the HIV‐specific T‐cell response in three HIV‐infected individuals. ELISpot assays were used to map peptide antigens. Many HIV peptides were mapped in all three individuals. However, there were several challenges and limitations associated with the deconvolution process. Peptides that induced low‐frequency responses or were masked by peptide competition within a given pool were not identified, because they did not meet the threshold criteria for a positive response. Also, amino acid sequence variation limited the ability of this method to map autologous HIV peptides. Alternative analysis strategies and revisions to the original matrix optimizations are presented that address ways to increase peptide identification. This optimized deconvolution method allows for efficient mapping of T‐cell peptide epitopes. It is rapid, powerful, efficient, and unrestricted by HLA type. Published 2008 Wiley‐Liss, Inc.
Statistical control for smart base-isolated buildings via cost cumulants and output feedback paradigm

A derivation of an output feedback solution to the statistical control problem which minimizes a finite linear combination of first k cost cumulants of the finite-horizon integral quadratic cost associated with a linear stochastic system, when the controller measures the noisy states is first presented. Of course for the k = 1 case, there has been the celebrated Kalman result. Also, there are already some results for infinite-horizon output-feedback risk sensitive control which minimizes a certain linear combination of denumerable cost cumulants. The contribution of this paper is to fill in the other values of k /spl ges/ 2 here, in hoping to complete the picture of linear k-cost-cumulant (kCC) control theory. The phase I benchmark problem for response control of smart base-isolated buildings then follows, in which the realistic 8-story, steel braced building representing mid rise buildings in the city of Los Angeles, California is protected by a linear elastometric isolation system under seven different earthquakes with fault normal and parallel components acting in two perpendicular directions. A group of nine non-dimensionalized evaluation criteria is used to assess the performance of both base isolation system and benchmark structure. Simulation results indicate that the active control of the augmenting devices at the isolation layer using output feedback statistical control paradigm offers broad improvement in structural performance over the baseline LQG design. Therefore, statistical control is well applicable to the protection of civil structures.
Clinical Characteristics of Primary Epstein Barr Virus Hepatitis with Elevation of Alkaline Phosphatase and γ-Glutamyltransferase in Children

Purpose The aim of the present study was to evaluate the clinical characteristics of the primary Epstein-Barr virus (EBV) hepatitis with elevation of both serum alkaline phosphatase (ALP) and γ-glutamyltransferase (γ-GT) levels in children. Materials and Methods A retrospective study was performed by reviewing of the medical records of 36 patients who were diagnosed with primary EBV hepatitis. The patients were divided into 2 groups: patients with elevated serum ALP and γ-GT levels (group 1) and patients without (group 2). Results The classic features of infectious mononucleosis (fever, pharyngitis and/or tonsillitis, and cervical lymphadenitis) were seen in 20 (57.1%) of group 1 patients and 18 (50.0%) of group 2 patients. Hepatitis with elevated serum ALP and γ-GT levels were present in 14 (38.9%) of the all patients. Of these patients, Jaundice occurred in only 2 (5.6%). The mean levels of aspartate aminotransferase and alanine aminotransferase (ALT) as well as the number of patients with ALT greater than 400 IU/L were significantly different between the groups (177 IU/L vs. 94 IU/L, 418 IU/L vs. 115 IU/L, and 50.0% vs. 13.6%; p=0.001, p=0.001, p=0.026, respectively). The mean duration of elevated serum ALT levels was 17.5 days in group 1 and 9.0 days in group 2 (p=0.013). All patients recovered fully without any chronic or serious complications. Conclusion Primary EBV hepatitis with predominant biochemical abnormalities of the elevation of ALP and γ-GT is frequent and mostly anicteric. This may represent a benign disease, but a delay in recovery of liver function as well.
Nonlinear bending and stretching of a circular graphene sheet under a central point load

Understanding of the bending and stretching properties of graphene is crucial in guiding its growth and applications. In this paper, we investigate the deformation of a single layer, circular, graphene sheet under a central point load by carrying out molecular mechanics (MM) simulations. The bending and stretching of the graphene sheet are characterized by using the von Kármán plate theory. Stress concentrations near the loaded region and the boundary due to bending rigidity of the graphene sheet are highlighted. It is shown herein that, with properly selected parameters, the von Kármán plate theory can provide a remarkably accurate prediction of the graphene sheet behavior under linear and nonlinear bending and stretching.
Sheepskin effects and the returns to education in New Zealand: Do they differ by ethnic groups?

Sheepskin effects are the wage returns specific to educational credentials rather than to accumulated years of education. They can occur because credentials may signal workers’ productivity. Signalling high productivity may be more valuable for members of ethnic minority groups if employers practice statistical discrimination. Many studies estimate sheepskin effects indirectly, from non‐linear wage returns to schooling years that correspond to the “usual” time taken to complete a qualification, but such methods are likely to be biased. This study directly estimates sheepskin effects in New Zealand using a special survey with information on both years of education and qualifications received. The results show large sheepskin effects, with the returns to credentials exceeding the returns to years of education, especially for ethnic minorities.
Technical Change and Earnings in British Establishments

Recent empirical studies point to higher wages enjoyed by workers in environments where new technologies are intensively used. An examination of the 1984 and 1990 establishment-based WIRS reveals similar patterns. This paper argues that endogeneity bias is endemic in these results. Controlling for this endogeneity bias suggests that the estimated impact of new technologies on wages is seriously upward-biased. It is more likely that the earnings-technology correlation is driven by the impact of higher earnings on technical change rather than vice versa. Copyright 1997 by The London School of Economics and Political Science
Ex-Offenders and the Labour Market: A Review of the Discourse of Social Exclusion and Consequences for Crime and the New Deal

The growth of mass unemployment and concerns about crime in industrialised countries have been paralleled by an increasing preoccupation of policymakers with social exclusion. A key feature of the social exclusion discourse has been its emphasis on paid work as a mechanism of integration. The author outlines how ex-offenders are excluded from the labour market. The consequences for crime and implications for policy focused on the New Deal are also discussed. The key findings are that exclusion is as much a social and political phenomenon as an economic one. Consequently, the focus of the New Deal on reinforcing immediate labour-market attachment by enhancing individual employability is unlikely to succeed in reintegrating ex-offenders through work. The central challenge for policy remains the tackling of inequality in the labour market.
THE ECONOMIC DETERMINANTS OF ALCOHOL CONSUMPTION

In this paper is presented an analysis of the consumption patterns of beer, wine and spirits for Australia using data for the period 1955/56-1985/86. The validity of the demand theory hypotheses demand homogeneity and Slutsky symmetry has been tested using recently developed distributionÂ• free procedures. The findings were that (i) beer and wine were necessities and spirits a strong luxury; (ii) beer and spirits are specific complements; and (iii) the homogeneity and symmetry hypotheses are acceptable. Preference for wine consumption seems to be independent of preference for beer and spirits.
Consumer Choice and Segmentation in the Restaurant Industry

A model of restaurant choice is derived from a survey of consumers which supports restaurateurs' competitive strategies. Whereas consumers say that food type and food quality are the primary variables of restaurant choice, once a choice set appropriate to the occasion and segment has been evoked, a restaurant's style and atmosphere become the deciding factors. The three demographic segments which emerged from the study - students, well-to-do middle aged, and older people of moderate income - showed clear preferences best explained by differences in style. Thus restaurateurs are right to compete primarily on style. Given the importance of a seemingly unimportant attribute, determinant analysis might be the best way to discover the critical success factors in a local market.
Interleukin 33: an innate alarm for adaptive responses beyond Th2 immunity–emerging roles in obesity, intestinal inflammation, and cancer

Interleukin (IL)‐33, a member of the IL‐1 family, was originally described in 2005 as a potent initiator of type 2 immunity found during allergic inflammation and parasitic infections. IL‐33 has been shown to play important and potent roles bridging innate and adaptive immunity in the regulation of tissue homeostasis, injury, and repair. Recent discoveries have extended the range of functions for IL‐33 beyond type 2 conditions and its role as an alarmin at barrier sites, with emerging central roles for IL‐33 in T‐cell regulation, obesity, viral and tumor immunity. Here, we review the recent advances on how IL‐33 activity is regulated, its immunomodulatory properties on innate and adaptive cells, and the newly discovered roles of IL‐33 in obesity, intestinal inflammation, and tumorigenesis.
REDD+ projects and national-level Readiness processes: a case study from Kenya

The Bali Action Plan and Cancun agreements on Reducing Emissions from Deforestation and forest Degradation, plus forest conservation, sustainable management of forests and enhancement of forest carbon stocks (REDD+) have encouraged demonstration activities as part of Readiness and a step towards national approaches. This has enabled important growth in pilot and demonstration projects. Yet an understanding about how these projects are connected and contribute to national-level technical, policy, and institutional preparedness (Readiness) for REDD+ is lacking. This article examines the linkages between national processes and the private-sector-driven Kasigau Corridor REDD+ project in Kenya. The study reveals interesting cross-scale interactions that have increased over time and have high potential for harnessing national-level processes through lessons from the project level. Key innovations from the Kasigau Corridor Project include the implementation of REDD+ in dry forests, operationalization of conservation easements in the context of REDD+, and demonstration of potential ways of obtaining upfront finance for REDD+. The study also provides a number of key recommendations for Kenya and REDD+ in general, including official endorsement of stand-alone REDD+ projects under national Readiness schemes and exploring jurisdictional and nested REDD+ approaches. Additionally, more accommodating national-level frameworks for attracting private-sector engagement and investments, and for integrating, scaling-out, or scaling-up lessons from such projects, would be needed to enhance national REDD+ Readiness.
THE DECISION MAKING IN SELECTING ONLINE TRAVEL AGENCIES: AN APPLICATION OF ANALYTIC HIERARCHY PROCESS

The emergence of Internet‐based distribution channels has created both opportunities for and challenges to the travel agencies. Based on the customer‐value perspective, this study focused on exploring the relative weights of the nine proposed fundamental travel products from an Internet perspective. The study cohort comprised customers who had purchased room products from travel agencies websites, with data collected using a questionnaire survey. Customers were surveyed during a 3‐month period at Taipei International Airport. Excluding useless questionnaires resulted in 131 respondents, corresponding to a response rate of 18.71%. We found that privacy, safety, and product quality were the three most important factors influencing customer purchases of room products on the Internet. The results of this study have some implications for travel agencies—companies will need to make a significant investment in website design of safety mechanism, and the greater the effort managers make to alleviate these concerns, the more likely it is that consumers will visit and buy products on their website.
A study of petrol consumption using Spanish panel data

Methods are proposed for the estimation of equations for consumption categories subject to non-participation and other types of censoring using an unbalanced panel data set on petrol expenditures from the Spanish Continuous Family Expenditure Survey. The use of panel data allows one to deal with two issues that pose econometric problems when dealing with individual budget data. On one hand, unobserved time invariant heterogeneity is controlled for. On the other hand, the problem of censoring in the dependent variable is addressed and the measurement error induced by infrequent purchases is corrected. Results suggest the use of probabilities of purchase estimated from the temporal pattern of expenditure records in order to carry out this correction. The estimated demand system is subsequently used to simulate the effects of changes in the taxation of petrol.
Internet banking loyalty: evaluating the role of trust, satisfaction, perceived risk and frequency of use

This paper analyses the role of satisfaction, trust, frequency of use and perceived risk as antecedents of consumer loyalty to banking websites. While the literature usually focuses on the direct effects of these variables, special attention is paid here to evaluate their moderating effects on the relationship between satisfaction and loyalty. The results from a sample of 254 Spanish users of Internet banking services show that while satisfaction correlates positively with loyalty, the effect is significantly less intense with high levels of perceived risk. The results are similar for trust, which correlates more positively with high levels of perceived risk, but also when Internet banking is used less frequently. Managerial implications from these results are provided.
Weakness of scientific and technical culture of the public and consequences for the development of prevention actions

It has been known since the Platonician myth of the cave that people are slaves to appearance, that one only has access to a pale reflection of the truth. All knowledge necessarily begins by a rupture with habits, by not accepting things at face value and by systematic doubt, as Descartes recognized. However, to arrive at elements of perception of new risks, there has to be a distance between the worker who may be subjected to the risk and the risk itself or what conditions it. Until now, society has been able to develop occupational risk prevention methods and practices on relatively ‘simple’ subjects by imposing rules and by communicating on targeted subjects via different media forms. To do this, the relays which exist, for example in France inside the ‘Institution Prévention’ of the Social Security, have been able to promote useful activities alongside changes to the legislation. The change in society at work, which is exploring complexity and more specific work situations, has led to more and more enterprises and in certain cases employees themselves being asked to express an opinion concerning the risks they are likely to encounter. However, as pointed out for example by Miller, ∼95% of society is either indifferent to science or is interested but does not feel competent: how then is a risk analysis to be constructed without external assistance? What place should be given to experts who give advice and consequently what prevention can be proposed? Different ways forward based on extending the scope of expert evaluation or the application of the precautionary principle are described in this paper, which is not intended to contribute safe, ready-made solutions. During the consideration given to the preparation of this document, it appeared necessary to reposition the prevention culture of citizens as early as the training process of young people. The problems are discussed and areas with potential are described, but as for the solutions, prior experimentation is necessary within a framework of social confidence or modest interest.
The early experiences of local climate change adaptation in Norwegian compared with that of local environmental policy, Local Agenda 21 and local climate change mitigation

Norwegian experiences on local environmental policy, Local Agenda 21 (LA21), local climate change mitigation (CCM) and local climate change adaptation (CCA) are compared in this article. One conclusion is that local CCA lacks the normative impetus for local action that LA21 and local CCM have had, thus making it harder to include CCA in serious policy-making at the local level of governance. Another conclusion is that local CCA like mainstream local environmental policy, but unlike that of LA21 and local CCM, is exclusively framed in a local context. By focusing only on the local effects of climate change taking place locally, and not looking into possible local effects of climate change taking place elsewhere, climate change vulnerability assessments in rich countries like Norway tend to conclude on far less dramatic consequences than what is up in the general climate change debate. This way of framing climate change vulnerabilities may prove to be counterproductive for the purpose of gaining support for climate change adaptation, as well as mitigation policies.