Miracle-dz/UniFAR-FTUs huggingface dataset:
First-in-Human Study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics, and Pharmacodynamics, in Patients with Metastatic Cancer

Purpose: This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CH5132799. Experimental Design: Patients with metastatic solid tumors were eligible for the study. CH5132799 was administered orally once daily or twice daily in 28-day cycles. Results: Thirty-eight patients with solid tumors received CH5132799 at 2 to 96 mg once daily or 48 to 72 mg twice daily. The MTD was 48 mg on the twice-daily schedule but was not reached on the once daily schedule. DLTs were grade 3 elevated liver function tests (LFT), grade 3 fatigue, grade 3 encephalopathy, grade 3 diarrhea, and grade 3 diarrhea with grade 3 stomatitis; all DLTs were reversible. Most drug-related adverse events were grade 1/2. Diarrhea (34%) and nausea (32%) were the most common events. Mean Cmax and AUC0-24 in steady state at MTD were 175 ng/mL and 1,550 ng·h/mL, respectively, consistent with efficacious exposure based on preclinical modeling. Reduction in SUVmax with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) was observed in 5 of 7 patients at MTD. A patient with PIK3CA-mutated clear cell carcinoma of the ovary achieved a partial response by GCIG CA125 criteria and further, a heavily pretreated patient with triple-negative breast cancer had marked improvement in her cutaneous skin lesions lasting six cycles. Conclusion: CH5132799 is well tolerated at the MTD dose of 48 mg twice daily. At this dose, the drug had a favorable PK and PD profile and preliminary evidence of clinical activity. Clin Cancer Res; 20(23); 5908–17. ©2014 AACR.
Asymptotically Efficient Adaptive Strategies in Repeated Games Part I: Certainty Equivalence Strategies

This paper addresses the problem of dynamic decision making in an uncertain and competitive environment. A decision maker player 1 faces a system about which he has some parametric uncertainty, and which is affected also by the actions of other agents. We focus on a worst-case analysts from the viewpoint of player 1, using the simplified model of a repeated matrix game with lack of information on one side, where single-stage rewards are random but announced, and perfect observations are assumed. Certain ideas from the field of stochastic adaptive control are used to formulate performance criteria in a non-Bayesian setting, and to devise appropriate control strategies. The basic performance measure is the total reward accumulated by player 1 over all stages played; the purpose of player 1 is to guarantee that his expected total reward will be “close” to what he could guarantee under complete information. The present paper considers adaptive decision strategies of the Certainty Equivalence type, based on a modified Maximum Likelihood estimator, and studies their asymptotic long-term performance. A sequel paper will be devoted to “asymptotically optimal” strategies.
Approximation of Large Dynamic Games

We provide a framework for simplifying the analysis and estimation of dynamic games with many agents by using nonatomic limit game approximations. We show that that the equilibria of a nonatomic approximation are epsilon-Bayesian-Nash Equilibria of the dynamic game with many players if the limit game is continuous. We also provide conditions under which the Bayesian-Nash equilibrium strategy correspondence of a large dynamic game is upper hemicontinuous in the number of agents. We use our results to show that repeated static Nash equilibria are the only equilibria of continuous repeated games of imperfect public or private monitoring in the limit as N approaches innity. Extensions include: games with large players in the limit as N approaches innity; games with (discontinuous) entry and exit decisions; Markov perfect equilibria of complete information stochastic games with aggregate shocks; and games with private and/or imperfect monitoring. Finally we provide an application of our framework to the analysis of large dynamic auction platforms such as E-Bay using the nonatomic limit model of Satterthwaite and Shneyerov [33].
Identification and Estimation of Local Average Derivatives in Non-Separable Models Without Monotonicity

In many structural economic models there are no good arguments for additive separability of the error. Recently, this motivated intensive research on non-separable structures. For instance, in Hoderlein and Mammen (2007) a non-separable model in the single equation case was considered, and it was established that in the absence of the frequently employed monotonicity assumption local average structural derivatives (LASD) are still identified. In this paper, we introduce an estimator for the LASD. The estimator we propose is based on local polynomial fitting of conditional quantiles. We derive its large sample distribution through a Bahadur representation, and give some related results, e.g. about the asymptotic behaviour of the quantile process. Moreover, we generalize the concept of LASD to include endogeneity of regressors and discuss the case of a multivariate dependent variable. We also consider identification of structured non-separable models, including single index and additive models. We discuss specification testing, as well as testing for endogeneity and for the impact of unobserved heterogeneity. We also show that fixed censoring can easily be addressed in this framework. Finally, we apply some of the concepts to demand analysis using British Consumer Data. Copyright The Author(s). Journal compilation Royal Economic Society 2009
Environment Reporters in the 21st Century

"Environment Reporters in the 21st Century" is the story of specialized journalists who, because of their expertise, their experience, or their willingness, regularly write about environmental issues. This is the story of a relatively new journalistic beat, one that developed during the lifetime of the authors. This book provides a view of American journalism in the first decade of the new century, when newspapers and television were the major source of news in America. The authors have divided the work into three parts. The first, Environment Reporting, includes a review of the literature and a detailed explanation of the methodology of the current study. Part II, The Environment Reporters of the 21st Century, describes the results of the present research. Part III, The Craft: Telling the Environment Story, provides in-depth accounts of environment reporters at work. Was the first decade of the 21st century a golden age of environmental reporting? The final chapter puts this research in historical perspective, viewing it in terms of the economic decline of the newspaper business and of local television news. Environment reporters and their sources are eager to get news out, but not always in the same way, or at the same time. There is a constant struggle among the thousands of environmental activists, corporate public relations people, government officials, and scientists to frame the message in a way that is advantageous to their point of view. This has been called the great ecological communication war, the war between conflicting public relations forces to influence public policy. These competing interests need to understand how journalists think and function. This volume tells the story of environmental reporting imaginatively and innovatively.
Interoceptive awareness enhances neural activity during empathy

Empathy is a multicomponent function that includes sensorimotor, affective, and cognitive components. Although especially the affective component may implicate interoception and interoceptive awareness, the impact of interoception on empathy has never been evaluated behaviorally or neurophysiologically. Here, we tested how a preceding period of interoceptive awareness impacts and modulates neural activity during subsequent empathy. We used functional magnetic resonance imaging (fMRI) and measured the sequential interaction between interoception and empathy using fMRI in 18 healthy subjects. We found that the preceding interoceptive awareness period significantly enhanced neural activity during empathy in bilateral anterior insula and various cortical midline regions. The enhancement of neural activity during empathy in both interoceptive and empathy networks by preceding interoceptive awareness suggests a close relationship between interoception and empathy; thereby, interoception seems to be implicated to yielding empathy. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Microfinance and public policy : outreach, performance and efficiency

The goal of microfinance institutions (MFIs) is to help the poor to cope better with risk, take advantage of small income generating opportunities and empower themselves through organization. To have this impact on an increasing number of people MFIs need to be financially sound and sustainable. This volume argues that while there may be situations where MFIs can go up-scale and thus meet both objectives at the same time, there are other market configurations where it is very difficult or even impossible for an institution to break even, no matter how efficiently it runs its operations. This is particularly the case in rural, remote and sparsely populated areas. To take account of the variety of market and contextual constraints, this book argues that public policy should be guided by efficiency, being an overarching criterion accommodating different combinations of financial performance and social impact. A valuable contribution to the debate surrounding the performance and sustainability of microfinance, this volume examines the concept of efficiency in financial intermediation, how it is measured and how public policy can be geared to provide incentives to efficiency gains. The argument is illustrated by an empirical analysis of 45 MFIs from around the world. This is a co-publication with Palgrave Macmillan Publishers.
The devil is in the detail: deception and consistency over repeated interviews

ABSTRACT Research indicates that truthful statements typically contain more details than fabricated statements, and that truth tellers are no more consistent than liars over multiple interviews. In this experiment, we examine the impact of (i) multiple interviewers and (ii) reverse order recall on liars’ and truth tellers’ consistency and amount of reported detail over repeated recall attempts. Participants either took part in a mock crime (lying condition) or an innocent event (truth telling condition) which they were subsequently interviewed about in two separate interview phases. Truth tellers provided more details overall, and more reminiscent details than liars. There were no differences between veracity groups for the number of omissions made or repetitions reported. Despite the popular belief that inconsistency is a cue to deception, we found little support for the notion that consistency (or lack of consistency) offers a diagnostic cue to deception. We found little evidence that switching interviewer or recalling in reverse order induced inconsistencies in liars. In fact, due to the number of reminiscent details in truth tellers’ accounts, our findings suggest that accounts provided by liars tend to be slightly more consistent than those provided by truth tellers. Materials for this paper can be found at osf.io/hgvmk/.
Assessment of access to financial capital by rural people in Ghana: the case of the Upper East region

Financial capital (FC) can transform self-image, unlock potential and boost the productivity and well-being of the poor. This paper assesses the access to FC by rural people in the Upper East Region (UER) of Ghana. The study results showed that Rural Banks (RBs) are the main source of FC to rural people in UER with only 21% of them having access to FC from the RBs in pursuance of their livelihoods developments. It is recommended that the RBs and government among others should take pragmatic measures towards covering more rural people who constitute 84% of the population of UER.
Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations: The following recommendations for post-polypectomy endoscopic surveillance should be applied only after a high quality baseline colonoscopy with complete removal of all detected neoplastic lesions. 1 In the low risk group (patients with 1 – 2 tubular adenomas < 10 mm with low grade dysplasia), the ESGE recommends participation in existing national screening programmes 10 years after the index colonoscopy. If no screening programme is available, repetition of colonoscopy 10 years after the index colonoscopy is recommended (strong recommendation, moderate quality evidence). 2 In the high risk group (patients with adenomas with villous histology or high grade dysplasia or ≥10 mm in size, or ≥ 3 adenomas), the ESGE recommends surveillance colonoscopy 3 years after the index colonoscopy (strong recommendation, moderate quality evidence). Patients with 10 or more adenomas should be referred for genetic counselling (strong recommendation, moderate quality evidence). 3 In the high risk group, if no high risk adenomas are detected at the first surveillance examination, the ESGE suggests a 5-year interval before a second surveillance colonoscopy (weak recommendation, low quality evidence). If high risk adenomas are detected at first or subsequent surveillance examinations, a 3-year repetition of surveillance colonoscopy is recommended (strong recommendation, low quality evidence). 4 The ESGE recommends that patients with serrated polyps < 10 mm in size with no dysplasia should be classified as low risk (weak recommendation, low quality evidence). The ESGE suggests that patients with large serrated polyps (≥ 10 mm) or those with dysplasia should be classified as high risk (weak recommendation, low quality evidence). 5 The ESGE recommends that the endoscopist is responsible for providing a written recommendation for the post-polypectomy surveillance schedule (strong recommendation, low quality evidence).
Music Lexical Networks

Successful recognition of a familiar tune depends on a selection procedure that takes place in a memory system that contains all the representations of the specific musical phrases to which one has been exposed during one's lifetime. We refer to this memory system as the musical lexicon. The goal of the study was to identify its neural correlates. The brains of students with little musical training were scanned with functional magnetic resonance imaging (fMRI) while the student listened to familiar musical themes, unfamiliar music, and random tones. The familiar themes were selected from instrumental pieces well‐known to the participants; the unfamiliar music was the retrograde version of the familiar themes, which the participants did not recognize; and the random sequences contained the same musical tones but in a random order. All stimuli were synthesized and played with the sound of a piano, thereby keeping low‐level acoustical factors similar across conditions. The comparison of cerebral responses to familiar versus unfamiliar music reveals focal activation in the right superior temporal sulcus (STS). Re‐analysis of the data obtained in a previous study by Plailly et al. also points to the STS as the critical region involved in musical memories. The neuroimaging data further suggest that these auditory memories are tightly coupled with action (singing), by showing left activation in the planum temporale, in the supplementary motor area (SMA), and in the inferior frontal gyrus. Such a cortical organization of music recognition is analogous to the dorsal stream model of speech processing proposed by Hickok and Poeppel.
CsAP3: A Cucumber Homolog to Arabidopsis APETALA3 with Novel Characteristics

In our previous efforts to understand the regulatory mechanisms of cucumber unisexual flower development, we observed a stamen-specific down-regulation of the ethylene receptor CsETR1 in stage 6 female flowers of cucumber (Cucumis sativus L.). This down-regulation is correlated with the primordial anther-specific DNA damage that characterizes inappropriate stamen development in cucumber female flowers. To understand how CsETR1 is down regulated in the stamen, we characterized a cucumber MADS box gene homologous to Arabidopsis AP3, CsAP3. We demonstrated that CsAP3 is functionally equivalent to the Arabidopsis B-class MADS gene AP3. However, three novel characteristics of CsAP3 were found. These include firstly, binding and activating CsETR1 promoter in vitro and in vivo; secondly, containing a GV repeat in its C-terminus, which is conserved in cucurbits and required for the transcription activation; and thirdly, decreased expression as the node number increases, which is similar to that found for CsETR1. These findings revealed not only the conserved function of CsAP3 as a B-class floral identity gene, but also its unique functions in regulation of female flower development in cucumber.
A Genome-Wide Association Study Reveals Dominance Effects on Number of Teats in Pigs

Dominance has been suggested as one of the genetic mechanisms explaining heterosis. However, using traditional quantitative genetic methods it is difficult to obtain accurate estimates of dominance effects. With the availability of dense SNP (Single Nucleotide Polymorphism) panels, we now have new opportunities for the detection and use of dominance at individual loci. Thus, the aim of this study was to detect additive and dominance effects on number of teats (NT), specifically to investigate the importance of dominance in a Landrace-based population of pigs. In total, 1,550 animals, genotyped for 32,911 SNPs, were used in single SNP analysis. SNPs with a significant genetic effect were tested for their mode of gene action being additive, dominant or a combination. In total, 21 SNPs were associated with NT, located in three regions with additive (SSC6, 7 and 12) and one region with dominant effects (SSC4). Estimates of additive effects ranged from 0.24 to 0.29 teats. The dominance effect of the QTL located on SSC4 was negative (−0.26 teats). The additive variance of the four QTLs together explained 7.37% of the total phenotypic variance. The dominance variance of the four QTLs together explained 1.82% of the total phenotypic variance, which corresponds to one-fourth of the variance explained by additive effects. The results suggest that dominance effects play a relevant role in the genetic architecture of NT. The QTL region on SSC7 contains the most promising candidate gene: VRTN. This gene has been suggested to be related to the number of vertebrae, a trait correlated with NT.
Thermal/fluid characteristics of 3-D woven mesh structures as heat exchanger surfaces

The present work demonstrates the fabrication methodology of a 3-D, aluminum wire filament, bonded mesh deployed as a heat exchange surface. A model of the effective thermal conductivity of the mesh is developed. Apparatus to measure the coolant pressure-drop and heat transfer coefficient are described. Measurements are reported for fabricated test samples of varying thickness. Mesh Stanton number and friction factor correlations for a coolant with Prandtl number equal to 9.5 (chilled water) are reported. A heat exchanger performance evaluation, comparing the 3D woven mesh technology to another exchanger surface technology, is described. We have found that the weaving/wire bonding process must be carefully controlled to insure that target porosity, specific surface area and effective thermal conductivity are achieved. Effective thermal conductivities are found to be at least two-times larger than achieved in other comparable porous media configurations. Mesh friction factor and Stanton number are comparable to those achieved with other exchanger surface technologies. The exchanger performance comparison shows that exchangers having superior performance can be configured.
Mast Cells Are Early Responders After Hypoxia-Ischemia in Immature Rat Brain

Background and Purpose— Perinatal hypoxia-ischemia (HI) produces acute and prolonged inflammation of the brain. Mast cells (MCs), numerous in the pia and CNS of neonatal rats, can initiate inflammation attributable to preformed mediators. MCs contribute to HI brain damage in the neonatal rat; MC stabilization protects through 48 hours of reperfusion. Here we hypothesize that HI induces early MC migration, activation, and release of proinflammatory molecules. Methods— HI was induced by right CCA ligation and 75 minutes 8% oxygen. Histochemistry and immunocytochemistry described the time course of early cellular changes in the CNS. For neuroprotection by MC stabilization, pups were treated with Cromolyn (CR) during the initial 24 hours post-HI; brains were examined through 4 weeks. Results— Brain MC number and activation were elevated in ipsilateral hemisphere immediately after HI (P<0.05), before detection of cleaved caspase-3 in neurons (NeuN+; 2 hours post-HI), astroglial activation (GFAP+ with swollen cell body, 4 hours post-HI), or microglial activation (OX42+, 4 hours post-HI). TNF-&agr;–positive MCs were present in a subpopulation of MCs in control animals and the percent of TNF-&agr; MCs increased dramatically ipsilaterally immediately after HI (P<0.01). Microglial TNF-&agr; was evident at 4 hours; endothelial cells had no detectable TNF-&agr; until 48 hours post-HI. Cromolyn prevented MC migration, reduced brain damage/neuronal loss, glial activation, and brain atrophy through 4 weeks of recovery (P<0.05). Conclusions— MCs are early responders to HI in neonatal brain. MC stabilization provides lasting protection and suggests a new target for therapeutic interventions.
Secure Short-Cut Routing for Mobile IP

This paper describes the architecture and implementation of a mobile IP system. It allows mobile hosts to roam between cells implemented with 2-Mbps radio base stations, while maintaining Internet connectivity. The system is being developed as part of a course on wireless networks at Harvard and has been operational since March 1994. The architecture scales well, both geographically and in the number of mobile hosts supported. It supports secure short-cut routing to mobile hosts using the existing Internet routing system without change. The implementation demonstrates a robust, low complexity realization of the architecture, and provides trade-off opportunities between efficiency and cost. Measured performance of the mobile system is generally excellent. The system can handle a high rate of location updates, and routes packets almost as efficiently for mobile hosts as the Internet does for stationary hosts. We observe reasonable TCP behavior during hand-offs.