Miracle-dz/UniFAR-FTUs huggingface dataset:
Starving (or Fattening) the Golden Goose?: Generic Entry and the Incentives for Early-Stage Pharmaceutical Innovation

Over the last decade, generic penetration in the U.S. pharmaceutical market has increased substantially, providing significant gains in consumer surplus. What impact has this rise in generic penetration had on the rate and direction of early stage pharmaceutical innovation? We explore this question using novel data sources and an empirical framework that models the flow of early-stage pharmaceutical innovations as a function of generic penetration, scientific opportunity, firm innovative capability, and additional controls. While the aggregate level of early-stage drug development activity has increased, our estimates suggest a sizable, robust, negative relationship between generic penetration and early-stage pharmaceutical research activity within therapeutic markets. A 10% increase in generic penetration is associated with a 7.9% decline in all early-stage innovations in the same therapeutic market. When we restrict our sample to first-in-class pharmaceutical innovations, we find that a 10% increase in generic penetration is associated with a 4.6% decline in early-stage innovations in the same market. Our estimated effects appear to vary across therapeutic classes in sensible ways, reflecting the differing degrees of substitution between generics and branded drugs in treating different diseases. Finally, we are able to document that with increasing generic penetration, firms in our sample are shifting their R&D activity to more biologic-based (large-molecule) products rather than chemical-based (small-molecule) products. We conclude by discussing the potential implications of our results for long-run welfare, policy, and innovation.
Unified Exact Performance Analysis of Two-Hop Amplify-and-Forward Relaying in Nakagami Fading

We present a general two-parameter received signal-to-noise ratio (SNR) model for two-hop amplify-and-forward (AF) relaying. It encompasses AF schemes that select the relay gain as the reciprocal of a linear combination of the channel gain and the noise power of the incoming link, including all channel-noise-assisted, channel-assisted, and blind relay schemes. Moreover, the model is flexible enough to represent independent source and relay power allocations. A unified performance analysis is then developed for AF relaying over independent but nonidentically distributed Nakagami-m faded links, where m is an integer. Exact analytical expressions are derived for the cumulative-distribution function (cdf), probability density function (pdf), and moment-generating function (mgf) of the received SNR. Monte Carlo simulation results are provided to verify the results.
Gender Issues in Online Communities

The Internet is imagined as an all-inclusive technology that will allow everyone, regardless of social status, gender, or ability, to communicate equally. The full title of a recent book is The Control Revolution ( http://www.amazon.com/exec/obidos/ASIN/1891620193/computerprofessi ) : How the Internet is Putting Individuals in Charge and Changing the World We Know. But has the offline world really changed? Or is what is happening online merely a reflection of real-world power structures and communications?
Clawback Provision of SOX, Financial Misstatements, and CEO Compensation Contracts

Section 304 of the Sarbanes-Oxley Act (hereafter, SOX), commonly known as the clawback provision, entitles the Securities and Exchange Commission (SEC) to sue the CEO and CFO in an attempt to recover their incentive compensation based on misstated financial reports. Although a stream of literature investigates the effects of voluntary firm-initiated clawback provisions, this study explores the effects of the mandatory SOX clawback provision on the likelihood of financial misstatements and CEO compensation. We find a significant decrease in the association between CEO in-the-money option value and the likelihood of a financial misstatement surrounding SOX, suggesting the SOX clawback provision has been effective in reducing financial misstatements arising from CEO in-the-money stock options. To examine the effects of the SOX clawback provision on CEO compensation, we identify a set of misstatement firms with a high restatement likelihood where the CEOs are most likely concerned with the impact of the SOX clawback provision on their compensation. We find that compared with control firms, these misstatement firms with a high restatement likelihood where the CEO is the chair of the board exhibit an increase in CEO salaries between the pre- and post-SOX periods, suggesting that in the post-SOX period, powerful CEOs are able to receive higher salaries which are not subject to the SOX clawback provision.
IL-2 Signaling in Human Monocytes Involves the Phosphorylation and Activation of p59hck 1

The activating properties of IL-2 and the structure of the IL-2R on human monocytes are well characterized. However, relatively little is known about the biochemical mechanisms involved in IL-2 signal transduction in these cells. We investigated the role of protein tyrosine kinases (PTKs) in the activation of monocytes by IL-2. Incubation of monocytes with the PTK inhibitor herbimycin A (HA) resulted in the dose-dependent suppression of IL-2-induced monocyte tumoricidal activity. This inhibition was rather potent, as a concentration of HA as low as 0.5 μM caused a complete abrogation of cytolytic activity. Furthermore, HA markedly suppressed the ability of IL-2 to induce IL-1β, TNF-α, IL-6, and IL-8 mRNA expression and protein secretion by monocytes. Anti-phosphotyrosine immunoblotting demonstrated that IL-2 induced a rapid and time-dependent increase in tyrosine phosphorylation of several cellular proteins of molecular masses ranging from 35 to 180 kDa. Interestingly, IL-2 caused a significant up-regulation of the constitutive levels of hck PTK mRNA and protein relative to medium-treated cells as well as an increase in p59hck tyrosine phosphorylation. Finally, we demonstrated by in vitro kinase assay that the specific activity of p59hck PTK was also induced by IL-2 in monocytes. Thus, these data show that the activation of PTKs is required for the triggering of monocyte effector and secretory functions by IL-2 and strongly suggest that p59hck is a key participant in IL-2 signaling in human monocytes.
Automatic Result Verification by Complete Run-Time Checking of Computations

Two-Stage Programming (2SP) is an experimental programming language, the first implementation of the Specification-Consistent Coordination Model (SCCM). The SCCM proposes a new, mixed-paradigm (functional/imperative) approach to developing reliable programs based on complete run-time checking of computations with respect to a given specification. A 2SP program consists of a functional specification and an imperative coordination tightly connected to the specification. The coordination maps the specification to an imperative and possibly parallel/distributed program. Normal termination of a 2SP program execution implies the correctness of the computed results with respect to the specification, for that execution. We present the basic feautures of the SCCM/2SP, a new message-spassing system of 2SP with integrated run-time checking, and a larger case study. We show that 2SP provides: functional specifications, specification-consistent imperative coordinations, automatic run-time result verification and error detection, enhanced debugging support, and good efficiency.
Exploring the missing link – Empathy among dental students: An institutional cross-sectional survey

Background: Empathy plays an important role in healthy dentist and patient relationship. Hence, the aim of the study is to (a) to measure the self-reported empathy levels among dental undergraduate and postgraduate students. (b) To review the trend of changes in empathy level with experience, age, and gender among dental undergraduate and postgraduate students. Materials and Methods: This cross-sectional, questionnaire-based study was carried out in two private dental institutions situated in Sri Ganganagar, India, with a sample size of 978. Data were obtained from the 1 st to final year (BDS), interns, and postgraduate students from January to March 2015. An empathy level of students was assessed by the Jefferson Scale of Physician Empathy - Health Profession Students Version Questionnaire. An exploratory factor analysis using Kaiser′s criteria was undertaken to appraise the construct validity and dimensionality. Based on the results of the factor analysis, three factors were selected; labeled as "perspective taking," "compassionate care," and "standing in patient′s shoes. " Results: The majority of the students was female in a equivalent ratio of 1338:618. There were significant differences in empathy scores by gender and age (P < 0.01). The lowest and highest mean empathy scores were found in postgraduate (mean = 108.77, standard deviation [SD] =9.12) and 1 st year (mean = 117.23, SD = 14.19) dental students, respectively. Conclusion: Dental educators should consider the likely decline in empathy among students as early as possible and adopt communication teaching strategies to promote the development of empathy and reduce the risk of further decline.
Effect of English Language Comprehension on Achievement in Engineering Mathematics

This paper presents results of a study that investigates the effects of English language comprehension on the achievement in engineering Mathematics. The population of the study was the entire year one and two (National Diploma I and II) students of Waziri Umaru Federal Polytechnic, Birnin Kebbi, Nigeria (n<700). A sample of two hundred and eighty seven (287) students was selected using simple random sampling. Pearson correlation, paired samples t-test and Independent sample t-test were used to analyze data using SPSS version 20.0. The results obtained indicated a significant difference exists between word-based problems and wordless problems in engineering mathematics. It was also revealed that the medium of instruction influence the attainment of instructional objectives in mathematics. No significant relationship was observed between English language comprehension and performance in non worded problems in engineering mathematics. Although the mathematical ability and numerical manipulative skills of the students seems not to be affected by English language comprehension, the results showed a strong positive correlation between English language comprehension and engineering mathematics word problems.
Cost Complexity of Proactive Learning via a Reduction to Realizable Active Learning

Proactive Learning is a generalized form of active learning with multiple oracles exhibiting different reliabilities (label noise) and costs. We propose a general approach for Proactive Learning that explicitly addresses the cost vs. reliability tradeoff for oracle and instance selection. We formulate the problem in the PAC learning framework with bounded noise, and transform it into realizable active learning via a reduction technique, while keeping the overall query cost small. We propose two types of sequential hypothesis tests (denoted as SeqHT) that estimate the label of a given query from the noisy replies of different oracles with varying reliabilities and costs. We prove correctness and derive cost complexity of the proposed algorithms. This research is supported by grants from the National Science Foundation.
Variance Reduction via Lattice Rules

This is a review article on lattice methods for multiple integration over the unit hypercube, with a variance-reduction viewpoint. It also contains some new results and ideas. The aim is to examine the basic principles supporting these methods and how they can be used effectively for the simulation models that are typically encountered in the area of management science. These models can usually be reformulated as integration problems over the unit hypercube with a large (sometimes infinite) number of dimensions. We examine selection criteria for the lattice rules and suggest criteria which take into account the quality of the projections of the lattices over selected low-dimensional subspaces. The criteria are strongly related to those used for selecting linear congruential and multiple recursive random number generators. Numerical examples illustrate the effectiveness of the approach.
Cholinergic Deafferentation of Prefrontal Cortex Increases Sensitivity to Cross-Modal Distractors during a Sustained Attention Task

The effects of restricted cholinergic deafferentation of prefrontal cortex in rats on sustained attention were assessed. Attentional demands were increased by presentation of distractor stimuli in a different modality (auditory) or the same modality (visual) as target stimuli. Additionally, the effects of the regularity of the distractor on rats' ability to disregard this stimulus were assessed by testing different frequencies of stimuli for each modality. Cholinergically lesioned rats were more sensitive to the effects of auditory distractors than nonlesioned rats, whereas visual distractors of any frequency potently impaired the performance of all subjects. The effects of the auditory stimuli on attentional performance varied depending on the frequency of the tone. A tone with a predictable pattern enhanced signal detection in all rats. An irregular tone selectively impaired performance of rats with cholinergic lesions. Additional tests suggest that rats use the regular tone to time when to attend. Lesioned rats were impaired when the regular tone was presented with a more variable intertrial interval in a subsequent testing session, suggesting impairments in top-down control. In addition to changes in top-down control of attention, differential effects on performance based on the regularity of the tone suggest that stimulus properties encoded by bottom-up processes are also altered after lesioning. The current data suggest that cholinergic deafferentation of prefrontal cortex alters top-down and bottom-up processing of stimuli.
Procurement Auctions with Pre-award Subcontracting

To be the lowest bidder in procurement auctions, prime contractors commonly solicit subcontract bids at the bid preparation stage. A remarkable feature of the subcontract competition is that "winning is not everything"; the lowest subcontractor gets a job conditional on his prime contractor's successful bid. This paper makes the first attempt to establish a model for such pre-award subcontract competitions included in procurement auctions. I find that subcontractors strategically provide larger discounts on their bids in response to increasing competition among prime contractors. I thus clarify that the behavior results in an endogenous downward shift in the distribution of bidders' private information in the downstream auction as the number of rivals increases, or the reservation price drops. The result has a striking impact on the analysis of optimal reservation price and empirical identification of the bidder's cost distribution in procurement auctions.
Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis

Epigenetics is often defined as the study of heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. Epigenetic changes are established through multiple mechanisms that include DNA methylation, non-coding RNAs and the covalent modification of specific residues on histone proteins. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukemia, but that these changes by their very nature are malleable, and thus are amenable to treatment. Epigenetic based therapies have so far focused on the use of histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors, which tend to have more general and widespread effects on gene regulation in the cell. However, if a unique molecular pathway can be identified, diseases caused by epigenetic mechanisms are excellent candidates for the development of more targeted therapies that focus on specific gene targets, individual binding domains, or specific enzymatic activities. Designing effective targeted therapies depends on a clear understanding of the role of epigenetic mutations during disease progression. The Mixed Lineage Leukemia (MLL) protein is an example of a developmentally important protein that controls the epigenetic activation of gene targets in part by methylating histone 3 on lysine 4. MLL is required for normal development, but is also mutated in a subset of aggressive human leukemias and thus provides a useful model for studying the link between epigenetic cell memory and human disease. The most common MLL mutations are chromosome translocations that fuse the MLL gene in frame with partner genes creating novel fusion proteins. In this review, we summarize recent work that argues MLL fusion proteins could function through a single molecular pathway, but we also highlight important data that suggests instead that multiple independent mechanisms underlie MLL mediated leukemogenesis.
Optimal Monetary Policy and Technological Shocks in the Post-War US Business Cycle

This paper assesses the optimality of US monetary policy in the face of permanent technology shocks. We first identify these shocks and their effects on aggregate variables through a SVAR model by resorting to long-run restrictions. Second, we consider a standard sticky price–sticky wage model with optimal monetary policy. The DSGE model is estimated and tested on its ability to replicate the responses of key variables to technology shocks as previously identified. Our findings suggest that one cannot reject the hypothesis that US monetary policy has been optimal, either in the Volcker– Greenspan or the pre–Volcker periods.
Informed Dialogue: Using Research to Shape Education Policy Around the World

Introduction Concepts and Issues Research Utilization: Why It's Important, Why It's an Issue, Why It's Difficult What Do We Mean by Informed Policymaking? Why Education Policies Are So Difficult to Inform Approaches to Informing Policy for Education Utilization as Using Pre-Cooked Conclusions Utilization Stimulated by Providing Decision Makers with Data Informing Policy by Constructing Knowledge Case Studies of Use of Information in Policymaking Namibia: Consultation for Change, the Etosha Conference Conducting an Education Sector Assessment in Egypt Conducting an Education Policy Survey in Honduras Conducting an Education Policy Survey in Colombia Conducting a Participatory Sector Assessment in El Salvador Policy Dialogue as Organizational Learning in Paraguay Fitting It All Together: A Model to Inform Policy with Research-based Knowledge Bibliography Index
Editorial: Prosocial and Antisocial Behavior in Economic Games

In this Research Topic, a collection of research and review articles contribute to our understanding of the factors influencing human prosocial and antisocial behavior in economic games. Under the labels of “prosocial” and “antisocial” behavior we consider all those actions that help or hurt others, respectively. While the prosocial, bright side of human behavior has received much attention in more than two decades, its antisocial, dark side is far less studied. This Research Topic aims to combine both sides into a comprehensive account of human social behavior.
Transmural versus nontransmural in situ electrical impedance spectrum for healthy, ischemic, and healed myocardium

Electrical properties of myocardial tissue are anisotropic due to the complex structure of the myocardial fiber orientation and the distribution of gap junctions. For this reason, measured myocardial impedance may differ depending on the current distribution and direction with respect to myocardial fiber orientation and, consequently, according to the measurement method. The objective of this study is to compare the specific impedance spectra of the myocardium measured using two different methods. One method consisted of transmural measurements using an intracavitary catheter and the other method consisted of nontransmural measurements using a four-needle probe inserted into the epicardium. Using both methods, we provide the in situ specific impedance spectrum (magnitude and phase angle) of normal, ischemic, and infarcted pig myocardium tissue from 1 kHz to 1 MHz. Magnitude spectra showed no significant differences between the measurement techniques. However, the phase angle spectra showed significant differences for normal and ischemic tissues according to the measurement technique. The main difference is encountered after 60 min of acute ischemia in the phase angle spectrum. Healed myocardial tissue showed a small and flat phase angle spectrum in both methods due to the low content of cells in the transmural infarct scar. In conclusion, both transmural and nontransmural measurements of phase angle spectrum allow the differentiation among normal, ischemic, and infarcted tissue.
The Joint Sales Impact of Frequency Reward and Customer Tier Components of Loyalty Programs

We estimate the joint impact of the frequency reward and customer tier components of a loyalty program on customer behavior and resultant sales. We provide an integrated analysis of a loyalty program incorporating customers' purchase and cash-in decisions, points pressure and rewarded behavior effects, heterogeneity, and forward-looking behavior. We focus on four key research questions: (1) How important is it to combine both components in one model? (2) Does points pressure exist in the context of a two-component loyalty program? (3) How is the market segmented in its response to the combined program? (4) Do the programs complement each other in terms of the incremental sales they produce? Our most basic message is that the frequency reward and customer tier components of loyalty programs should be modeled jointly rather than in separate models. We find strong evidence for points pressure for both the customer tier and frequency reward components using both model-based and model-free evidence. We find a two-segment solution revealing a “service-oriented” segment that highly values cash-ins for room upgrades and staying in “luxury” hotels, and a “price-oriented” segment that is more price sensitive and highly values the frequency reward aspects of the loyalty program. Furthermore, we find that both components generate incremental sales. Also, there was slight synergy between the programs but not a huge amount. Overall, each component contributes to increased revenues and does not interfere with the other.
Path-dependent equations and viscosity solutions in infinite dimension

Path Dependent PDE's (PPDE's) are natural objects to study when one deals with non Markovian models. Recently, after the introduction (see [12]) of the so-called pathwise (or functional or Dupire) calculus, various papers have been devoted to study the well-posedness of such kind of equations, both from the point of view of regular solutions (see e.g. [18]) and viscosity solutions (see e.g. [13]), in the case of finite dimensional underlying space. In this paper, motivated by the study of models driven by path dependent stochastic PDE's, we give a first well-posedness result for viscosity solutions of PPDE's when the underlying space is an infinite dimensional Hilbert space. The proof requires a substantial modification of the approach followed in the finite dimensional case. We also observe that, differently from the finite dimensional case, our well-posedness result, even in the Markovian case, apply to equations which cannot be treated, up to now, with the known theory of viscosity solutions.