Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers of Resistance to Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients with Metastatic Colorectal Cancer

Genomics and proteomics have held out the promise of individualized medicine for the last 10 or 20 years, but clinical medicine has not yet delivered on this promise. Some cancers, such as breast cancer and some hematologic malignancies, have been at the forefront of individualized therapeutic approaches by integrating molecular biomarkers into treatment decision algorithms. Until recently, the treatment of colorectal cancer (CRC) has lagged behind these other cancers in this regard and therapeutic decisions have been solely empirical. Data from various clinical trials and translational studies have now opened the door for individualized treatment approaches by identifying patients with metastatic CRC who are most likely to benefit from antibodies against the epidermal growth factor receptor (EGFR), cetuximab and panitumumab. Activating mutations of KRAS, a downstream mediator of EGFR signaling, has been shown to render EGFR antibodies ineffective, such that analyzing tumors for these mutations has become mandatory before the use of EGFR antibodies is considered in CRC. Beyond KRAS, several additional biomarkers are currently being investigated as potential positive or negative predictors for the efficacy of EGFR-targeted therapy. Most of these markers are alterations of molecules integrated in the EGFR pathway. This review will focus on the type and quality of evidence that has been gathered to date to predict resistance to monoclonal antibodies against EGFR in CRC. (Clin Cancer Res 2009;15(24):7492–501)
A New Multi-Criteria ABC Inventory Classification Model Based on a Simplified Electre III Method and the Continuous Variable Neighborhood Search

ABC analysis is one of the most widely used techniques in inventory management to classify items into three ordered categories called A, B and C, where category A contains the most important items and category C includes the least important ones. The ABC classification of inventory items is based on their performance expressed by weighted scores. In this paper, a new ABC classification model based on a simplified ELECTRE III method will be used as an aggregation procedure to compute the items scores. Since the application of the simplified ELECTRE III requires the knowledge of some parameter values (e.g. indifference, preference and veto thresholds), the Continuous Variable Neighborhood Search (CVNS) metaheuristic is used for their estimation. To analyze the performance of the proposed classification model with respect to some existing models, a benchmark dataset from an Hospital Respiratory Therapy Unit (HRTU) is used
Modeling Snow Volume Backscatter Combining the Radiative Transfer Theory and the Discrete Dipole Approximation

A new method is developed to model the volume backscattering from dry snow. The model is a combination of the exact field approach and zeroth order vector radiative transfer theory. The field approach is used to define the scattering characteristics in a single almost indefinite small snow volume unit and the calculation is realized with discrete dipole approximation (DDA). The radiative transfer theory (RT) is utilized by defining a homogenous snow layer from the averaged scattering characteristics and combining different layers together forming a vertical structure of a snow pack. Because of the DDA the presented model takes into account all multiple reflections and all polarizations inside the snow volume. The scattering amplitude values calculated with the DDA method and according to Mie theory are compared to together. Some results for a homogeneous snow layer are presented for both cubical and needle shaped snow grains.
Frontiers in Synaptic Neuroscience Synaptic Neuroscience

A major problem in investigating the functional role of dopamine signals for synaptic plasticity is that it has been technically challenging to manipulate its levels in a physiological meaningful way. In the present study, therefore, we deployed procedures that have been shown previously to evoke the release of dopamine by more natural means (Coizet et al., 2003; Comoli et al., 2003; Dommett et al., 2005). In urethane anesthetized rats, disinhibition of the superior colliculus (SC) by a local injection of the GABA A antagonist bicuculline (BIC) enables visual-evoked activation of dopaminergic neurons. Thus, a visual event can activate dopaminergic neurons via a subcortical pathway from retinal ganglion cells through the SC. In parallel, a tecto-thalamo-striatal pathway mediates excitatory inputs that rapidly depolarize spiny projection neurons (SPN), the principal neurons of the striatum, in response to the same sensory event (Schulz et al., 2009). Therefore, for the first time it was possible to control these subcortical inputs to the striatum using a physiological stimulus during intracellular recordings from SPNs. This study investigated how visual-evoked inputs from tecto-striatal pathways affected the outcome of conventional plasticity protocols on the cortico-striatal synapse. The visual stimulus was delivered at a short, physiological meaningful delay as suggested by theoretical work (Izhikevich, 2007) and our previous experience (Reynolds et al., 2001). First, we measured cortico-striatal
The Neglect of Africa and the Power of Aid

Since the end of colonial rule, Africa has on the whole been inadequately covered by the western media. It is rarely reported except as a backdrop to disaster or as the scene of a celebrity visit. There is an absence of sustained and well-informed reporting about Africa in the mainstream media. And when the media do cover it they often get the story very wrong, partly because there is no ongoing understanding of and engagement with the continent. Using exclusive access to the BBC archive, the article examines how and why media coverage of Africa has been misleading and misinformed in the postcolonial period. It examines the extent to which the close relationship between media coverage and aid agencies has damaged the cause of informing the public. Aid agencies have seen a huge growth since the mid-1980s - partly precipitated by the power of media imagery. As media organizations have reduced their commitment to investing in reporting on Africa so journalists have in turn become more dependent upon aid agencies, which have filled a vacuum. This symbiotic relationship requires a degree of transparency otherwise there is a danger that it can compromise journalistic accountability.
Illegal Abortion in Southern Ghana: Methods, Motives and Consequences

This paper provides information on various aspects of illegally induced abortion among the Akan in southern Ghana. Discussed are the frequency of abortion, the techniques, the social circumstances in which it takes place, its medical, juridical and educational consequences, and value judgements about it. The most important conclusion is that the restrictiveness of the Ghanaian legislation has not been able to prevent or limit the incidence of abortion. Its outlawing has rather led to the use of dubious and highly dangerous means of causing abortion. Young women are the main victims of the present situation, both in terms of unequal educational opportunities and in terms of physical damage caused to them. A more appropriate family planning policy in combination with a legalization of abortion seems a reasonable solution.
Ability of Vibrio vulnificus to obtain iron from hemoglobin-haptoglobin complexes

It has been suggested that the normal serum protein, haptoglobin (Hp), serves a bacteriostatic role by binding free hemoglobin (Hm), thus making heme iron unavailable for bacterial growth. Previous studies showed that, unlike Escherichia coli, Vibrio vulnificus was able to overcome this Hp-blocking effect. We report here a study on the iron-withholding property of the three major human Hp phenotypes, Hp 1, 2, and 2-1. Results of experiments with human serum showed that V. vulnificus C7184 was able to obtain iron from Hm bound to Hp types 1 and 2, but not that bound to Hp 2-1. E. coli 2395-80, on the other hand, was unable to overcome the blocking effect of any Hp phenotype. Using purified Hp 1, we also demonstrated that, although V. vulnificus was unable to grow in a deferrated medium without an additional iron source, it was able to grow with the addition of the Hm-Hp complex.
Calculating Home Advantage in the First Decade of the 21th Century UEFA Soccer Leagues

Abstract Home advantage has been studied in different sports, establishing its existence and its possible causes. This article analyzes the home advantage in soccer leagues of UEFA countries in the first part of the 21st century. The sample of 52 countries monitored during a period of 10 years allows us to study 520 leagues and 111,030 matches of the highest level in each country associated with UEFA. Home advantage exists and is significant in 32 of the 52 UEFA countries, where it equals 55.6%. A decrease can be observed in the tendency towards home advantage between the years 2000 and 2010. Values between 55 and 56 were observed for home advantage in the top ten leagues in Europe. It has also been observed that home advantage depends on the level of the league evaluated using UEFA’s 2010/11 Country coefficients. The home advantage is calculated taking into account the teams’ position and the points obtained in each of the leagues. A direct relationship was observed with the number of points gained and an inverse relationship was observed with the team position.
Is Facebook Linked to Selfishness? Investigating the Relationships among Social Media Use, Empathy, and Narcissism

The rise of social networking sites have led to changes in the nature of our social relationships, as well as how we present and perceive ourselves. The aim of the present study was to investigate the relationship among the following in adults: use of a highly popular social networking site—Facebook, empathy, and narcissism. The findings indicated that some Facebook activities, such as chatting, were linked to aspects of empathic concern, such as higher levels of Perspective Taking in males. The Photo feature in Facebook was also linked to better ability to place themselves in fictional situations. For only the females, viewing videos was associated with the extent to which they could identify with someone’s distress. The data also indicated that certain aspects of Facebook use, such as the photo feature, were linked to narcissism. However, the overall pattern of findings suggests that social media is primarily a tool for staying connected, than for self-promotion.
Qualitative Data Archiving: Some Reflections on its Prospects and Problems

The archiving of qualitative data seems likely to become much more common in the future. It promises to make an important contribution to the development of sociological research. This contribution relates to at least two main areas. It should facilitate assessment of the validity of particular studies; and it ought to increase the scope for secondary analysis. At the same time, the archiving of qualitative data and its use are not without problems. This paper examines both the possibilities it opens up and the limits to the contribution it can make.
Attitude strength: One construct or many related constructs?

A variety of attributes differentiate attitudes that are stable and conseguential from those that are not, including extremity, certainty, importance, knowledge, intensity, interest, direct experience, accessibility, latitudes of rejection and noncommitment, and affective-cognitive consistency. Although these dimensions are clearly conceptually and operationally distinct from one another, researchers have often assumed that some are interchangeable, or that two or more reflect common higher-order constructs. Three studies using multitrait-multimethod confirmatory factor analysis assessed the relations among these dimensions. Although some of these dimensions are strongly related, most are not, and a multifactor model seems necessary to account for their intercorrelations
Is talking about an emotional experience helpful? Effects on emotional recovery and perceived benefits

People generally share their emotions with others and believe that they will recover from their emotions after having talked about them. The aims of the present studies were to examine whether (1) talking about a specific emotional episode really facilitates emotional recovery ('recovery' effect) and (2) talking about emotions leads to perceived benefits ('perceived benefits'). Consistently in the two studies, a decrease of emotional impact was found over time for participants in all conditions. Contrary to expectations, participants assigned to talk about their emotions did not demonstrate beneficial recovery effects at 3 or 7 days or 2 months compared with participants assigned to a factual description of the event (experiment 1), to the expression of another emotional event (experiment 2), to a trivial control condition (experiments 1 and 2) or to a non-talking condition (experiment 2). However, in the two experiments, participants assigned to talk about negative emotional experiences reported more subjective benefits from the session than control participants. The role of personal beliefs about the effects of social sharing of emotion is discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.
Drug-Class Specific Impact of Antivirals on the Reproductive Capacity of HIV

Predictive markers linking drug efficacy to clinical outcome are a key component in the drug discovery and development process. In HIV infection, two different measures, viral load decay and phenotypic assays, are used to assess drug efficacy in vivo and in vitro. For the newly introduced class of integrase inhibitors, a huge discrepancy between these two measures of efficacy was observed. Hence, a thorough understanding of the relation between these two measures of drug efficacy is imperative for guiding future drug discovery and development activities in HIV. In this article, we developed a novel viral dynamics model, which allows for a mechanistic integration of the mode of action of all approved drugs and drugs in late clinical trials. Subsequently, we established a link between in vivo and in vitro measures of drug efficacy, and extract important determinants of drug efficacy in vivo. The analysis is based on a new quantity—the reproductive capacity—that represents in mathematical terms the in vivo analog of the read-out of a phenotypic assay. Our results suggest a drug-class specific impact of antivirals on the total amount of viral replication. Moreover, we showed that the (drug-)target half life, dominated by immune-system related clearance processes, is a key characteristic that affects both the emergence of resistance as well as the in vitro–in vivo correlation of efficacy measures in HIV treatment. We found that protease- and maturation inhibitors, due to their target half-life, decrease the total amount of viral replication and the emergence of resistance most efficiently.
The effect of noradrenaline and tyramine on cardiac contractility, cyclic AMP, and phosphorylase a in normal and hyperthyroid rats.

Noradrenaline and tyramine increased contractility, phosphorylase a, and cyclic AMP in a dose-dependent manner in the isolated perfused rat heart. Time–response studies revealed that cyclic AMP was increased by both amines before the increase in contractility. Hearts from hyperthyroid rats responded to noradrenaline in a manner similar to control hearts when contractility or cyclic AMP was measured. The phosphorylase activating effect of noradrenaline was enhanced in the hyperthyroid hearts. It was concluded that a non-cyclic AMP mechanism was involved in the enhancement. The effects of tyramine on contractility and cyclic AMP were decreased in the hearts from hyperthyroid animals when compared with control hearts. Phosphorylase activation by tyramine was not enhanced by the hyperthyroid state and was in fact reduced at higher doses of tyramine.
Massachusetts Institute of Technology Department of Economics Working Paper Series Sparse Models and Methods for Optimal Instruments with an Application to Eminent Domain Sparse Models and Methods for Optimal Instruments with an Application to Eminent Domain

We develop results for the use of LASSO and Post-LASSO methods to form first-stage predictions and estimate optimal instruments in linear instrumental variables (IV) models with many instruments, p, that apply even when p is much larger than the sample size, n. We rigorously develop asymptotic distribution and inference theory for the resulting IV estimators and provide conditions under which these estimators are asymptotically oracle-efficient. In simulation experiments, the LASSO-based IV estimator with a data-driven penalty performs well compared to recently advocated many-instrument-robust procedures. In an empirical example dealing with the effect of judicial eminent domain decisions on economic outcomes, the LASSO-based IV estimator substantially reduces estimated standard errors allowing one to draw much more precise conclusions about the economic effects of these decisions. Optimal instruments are conditional expectations; and in developing the IV results, we also establish a series of new results for LASSO and Post-LASSO estimators of non-parametric conditional expectation functions which are of independent theoretical and practical interest. Specifically, we develop the asymptotic theory for these estimators that allows for non-Gaussian, heteroscedastic disturbances, which is important for econometric applications. By innovatively using moderate deviation theory for self-normalized sums, we provide convergence rates for these estimators that are as sharp as in the homoscedastic Gaussian case under the weak condition that log p = o(n 1/3). Moreover, as a practical innovation, we provide a fully data-driven method for choosing the user-specified penalty that must be provided in obtaining LASSO and Post-LASSO estimates and establish its asymptotic validity under non-Gaussian, heteroscedas-tic disturbances. Preliminary results of this paper were first presented at Chernozhukov's invited Cowles Foundation lecture at the Northern American meetings of the Econo-metric society in June of 2009. We thank seminar participants at Brown, Columbia, Harvard-MIT, the Dutch Econometric Study Group, Fuqua School of Business, and NYU for helpful comments. We also thank Denis Chetverikov, JB Doyle, and Joonhwan Lee for thorough reading of this paper and helpful feedback.
Linear Logic Proof Games and Optimization

§ 1. Introduction. Perhaps the most surprising recent development in complexity theory is the discovery that the class NP can be characterized using a form of randomized proof checker that only examines a constant number of bits of the “proof” that a string is in a language [6, 5, 31, 3, 4]. More specifically, writing ∣x∣ for the length of a string x, a language L in the class NP of languages recognizable in Nondeterministic polynomial time is traditionally given by a polynomial p and a polynomial-time predicate P such that a string x is in L iff there is some string y satisfying P(x, y), where ∣y∣ ≤ p (∣x∣). Intuitively, we can think of a string y as a possible proof that x ϵ L, with the predicate P some kind of proof checker that distinguishes good proofs from bad ones. A string x is therefore in a language L ϵ NP if there is a short proof that x ϵ L, and not in L otherwise. The surprising discovery is that the deterministic proof checker that reads the entire input and proof can be replaced by a probabilistic verifier that on input x and possible proof y, where y is presented in a certain way, flips at most O (log ∣x∣) coins and reads at most a constant number of bits of x and y. Obviously, a probabilistic verifier that does not read the whole proof will sometimes make mistakes. However, the surprising and essentially non-intuitive mathematical fact is that for each language L in NP, it is possible to find a polynomial q and verifier V flipping a logarithmic number of coins and reading a constant number of bits such that, for any x ϵ L, there exists y with ∣y∣ ≤ q(∣x∣) and with V (x, y) accepting with probability 1 and, for x ∉ L, there is no y with ∣y∣ ≤ q(∣x∣) and with V (x, y) accepting with probability ≥ 1/4. This idea canalsobeextended to PSPACE [10, 9], using a game that alternates between two players instead of a proof presented by a “single player. ”
Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants.

Chronic exposure of pancreatic islets to supraphysiologic concentrations of glucose causes adverse alterations in beta cell function, a phenomenon termed glucose toxicity and one that may play a secondary pathogenic role in type 2 diabetes. However, no mechanism of action has been definitively identified for glucose toxicity in beta cells. To ascertain whether chronic oxidative stress might play a role, we chronically cultured the beta cell line, HIT-T15, in medium containing 11.1 mM glucose with and without the antioxidants, N-acetyl-L-cysteine (NAC) or aminoguanidine (AG). Addition of NAC or AG to the culture medium at least partially prevented decreases in insulin mRNA, insulin gene promoter activity, DNA binding of two important insulin promoter transcription factors (PDX-1/STF-1 and RIPE-3b1 activator), insulin content, and glucose-induced insulin secretion. These findings suggested that one mechanism of glucose toxicity in the beta cell may be chronic exposure to reactive oxygen species, i.e., chronic oxidative stress. To ascertain the effects of these drugs on diabetes, NAC or AG was given to Zucker diabetic fatty rats, a laboratory model of type 2 diabetes, from 6 through 12 weeks of age. Both drugs prevented a rise in blood oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde + 4-hydroxy-2-nonenal), and partially prevented hyperglycemia, glucose intolerance, defective insulin secretion as well as decrements in beta cell insulin content, insulin gene expression, and PDX-1 (STF-1) binding to the insulin gene promoter. We conclude that chronic oxidative stress may play a role in glucose toxicity, which in turn may worsen the severity of type 2 diabetes.
Measuring the intrinsic benefits of arts attendance

There is an emerging dissatisfaction with the current evaluative regimes for the quality and effectiveness of funded arts organizations. Far too much evaluation rests on audience satisfaction surveys and quantitative measures of audience attendance numbers, production numbers and revenue sources. The intrinsic benefits of the arts to audiences and to society are recognized to be of major importance, but the means to measure these in an acceptable and on-going manner has not been found. This article changes that. It shows, through almost three years of data collection on arts audiences, that a newly developed and tested Arts Audience Experience Index can be used and embedded by companies and government funding agencies to measure the audience experience of quality, alongside other acquittal tools.