Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Gene Expression and Cell-Cycle Signaling Pathways by the EGFR Inhibitor Gefitinib (Iressa) in Rat Urinary Bladder Cancer

The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10−15 (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10−42 (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10−8 and r = 0.73, P = 1.50 × 10−65, respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. Cancer Prev Res; 5(2); 248–59. ©2011 AACR.
Molecular Cloning of NKp46: A Novel Member of the Immunoglobulin Superfamily Involved in Triggering of Natural Cytotoxicity

NKp46 has been shown to represent a novel, natural killer (NK) cell–specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of NKp46 in natural cytotoxicity against different tumor target cells. We provide direct evidence that NKp46 represents a major activating receptor involved in the recognition and lysis of both human and murine tumor cells. Although NKp46 may cooperate with other activating receptors (including the recently identified NKp44 molecule) in the induction of NK-mediated lysis of human tumor cells, it may represent the only human NK receptor involved in recognition of murine target cells. Molecular cloning of the cDNA encoding the NKp46 molecule revealed a novel member of the immunoglobulin (Ig) superfamily, characterized by two C2-type Ig-like domains in the extracellular portion. The transmembrane region contains the positively charged amino acid Arg, which is possibly involved in stabilizing the association with CD3ζ chain. The cytoplasmic portion, spanning 30 amino acids, does not contain immunoreceptor tyrosine-based activating motifs. Analysis of a panel of human/hamster somatic cell hybrids revealed segregation of the NKp46 gene on human chromosome 19. Assessment of the NKp46 mRNA expression in different tissues and cell types unambiguously confirmed the strict NK cell specificity of the NKp46 molecule. Remarkably, in line with the ability of NKp46 to recognize ligand(s) on murine target cells, the cDNA encoding NKp46 was found to be homologous to a cDNA expressed in murine spleen. In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity.
A Multi-modal Biometric Fusion Implementation for ABC Systems

In this paper, we introduce a multi-modal approach for traveller biometric identity verification, in the context of the Spanish Automated Border Control (ABC) implementation. An ABC is an automated system which reads and authenticates the electronic travel document, verifies the identity of the document holder, performs background checks and resolves the eligibility for border crossing. This paper focuses on the second stage of the automated process, the identity verification, based on the biometric data available in the electronic travel document. According to the nature of the travel document, a standardized facial image (1st and 2nd generation electronic Passport, Spanish electronic ID card), two standardized fingerprint images (2nd generation electronic Passport) or fingerprint Match-on-Card features (Spanish electronic ID card) are available. While the facial image can be considered the de facto standard biometric modality for ABC systems, fingerprint availability allows for security enhancement and false rejection rates improvement.
Steps Towards A Basic Theory Of Groups

The 20th-century is the century of the group. In this century we have seen a re-emergence of interest in and awareness of the central importance of our group life, of man as a social creature. We can contrast this with the 19th-century where psychology emphasized man as an individual and where we saw the emergence of the great schools of individual psychology, such as psychoanalysis. These both paralleled and were influenced by the discovery of the evolutionary process of phylogeny and ontogeny. Thus, in one century we had the work of Darwin in biology, the discovery or (invention) of childhood as a development in its own right, which led to pedagogy, and the rise of sociology. There was a confluence of these trends in the creation of a new science of social psychology. Theories emerged that pointed to a continuum in nature, that embodied evolutionary principles and which paid due respect to the special characteristics of the organism or of the individual at each developmental level. One such continuum is that of automatism to the autonomous. Automatism is manifested by the unthinking routine of living beings whose actions are involuntary and who are without the substantial use of active intelligence, whereas the autonomous organism displays a personal freedom with a right to self-regulation. (The autonomous being if subject to external law becomes heteronomous.) The lower animals are characterized by automatic instinctive behaviour, invariant and unlearned, controlled by genetic and hormonal influences. Erikson has said that lower forms have relatively inborn, relatively early, ready to use ways of interacting with a segment of nature as part of which they have survived. In the higher 579396 GAQ0010.1177/0533316415579396Group AnalysisPines: A Basic Theory of Groups research-article2015
Cooperative Interaction between the Basic Helix-loop-helix Transcription Factor dHAND and Myocyte Enhancer Factor 2C Regulates Myocardial Gene Expression*

Cardiac-restricted transcription factors dHAND and myocyte enhancer factor 2C are expressed in the developing heart and activate several cardiac promoters. However, their regulatory mechanisms are still to be understood. To elucidate their exact regulatory functions, we have developed an RNA interference strategy to specifically inhibit dHAND and myocyte enhancer factor 2C protein production in H9c2 cells, which are derived from rat embryonic heart. Expression of endogenous cardiac genes atrial natriuretic peptide and α-myosin heavy chain was down-regulated in H9c2 cells lacking both dHAND and myocyte enhancer factor 2C, indicating that these factors are required for the maintenance of the cardiac genetic program. Consistent with these, expression of atrial natriuretic peptide and α-myosin heavy chain was up-regulated in H9c2 cells, which overexpressed dHAND and myocyte enhancer factor 2C. In addition, dHAND and myocyte enhancer factor 2C interact to synergistically activate atrial natriuretic peptide and α-myosin heavy chain transcription. Furthermore, chromatin immunoprecipitation analysis in H9c2 cells treated with phenylephrine showed that dHAND and myocyte enhancer factor 2C protein complex bind to the A/T sequence on atrial natriuretic peptide promoter. Taken together, these results not only suggest that the complex cis-trans interaction of dHAND, myocyte enhancer factor 2C, and the target gene may fine-tune gene expression in cardiac myocytes but also provide a molecular paradigm to elucidate the mechanisms of action of dHAND and myocyte enhancer factor 2C in the developing heart.
Performance of Incremental AF Relaying Cooperative Networks with the nth Best Relay over Rayleigh Fading Channels

Cooperative diversity networks have recently been proposed as a promising technology to improve performance over fading channels. In this paper, we consider incremental amplify-and-forward (AF) cooperative diversity networks which employ the N th best relay when the best relay is unavailable due to issues such as scheduling or load balancing. The end-to-end performance is analyzed over independent and identical (i.i.d.) and nonidentical (i.n.d.) Rayleigh fading channels. Closed form expressions for the bit error rate and channel capacity are derived, and results are presented to illustrate the performance. According to the analysis, The incremental AF strategy can reduce BER greatly when comparing to the conventional direct communication without cooperative, although it can not get the capacity of conventional direct communication, which is with the power as the total power of soure and N th best relay node in AF cooperative network. The incremental AF strategy with N th best relay can improve the capacity in high SNR region comparing to the complete cooperative with N th best relay when BER can be accepted by setting different threshold for SNR of the direct link between source node S and destination node D . The incremental N th best relay cooperative protocol can be useful when considering improving the error rate and bandwidth efficiency at the same time comparing to the conventional direct system and complete cooperative
Recommending Personalized Query Revisions

Observing the queries selected by a user, among those suggested by a recommender system, one can infer constraints on the user’s utility function, and can avoid suggesting queries that retrieve products with an inferior utility, i.e., dominated queries. In this paper we propose a new e ffi cient technique for the computation of dominated queries. It relies on the system’s assumption that the number of possible profiles (or utility functions), of the users it may interact with, is finite. We show that making query suggestions is simplified, and the number of suggestions is strongly reduced. We also found that even if the system is not contemplating the true user profile, among the above mentioned finite set of profiles, its performance is still very close to the optimal one.
Longitudinal Pedagogy: A Successful Response to the Fragmentation of the Third-Year Medical Student Clerkship Experience

A longitudinal clerkship was designed at Harvard Medical School (HMS) in 2004–2005 to emphasize continuity, empathy, learner-centeredness, and patient-centered care. In 2005–2006, the curriculum was piloted with eight students who voluntarily enrolled in the third-year curriculum, which focused on longitudinal mentorship and feedback, interdisciplinary care, integration of clinical and basic science, and humanism in patient care. Eighteen traditional curriculum (TC) students at HMS who were comparable at baseline served as a comparison group. SHELF exams and OSCE performance, monthly and end-of-year surveys, and focus groups provided comparisons between pilot and TC students on their performance, perceptions, attitudes, and satisfaction. Pilot students performed as well as or better than their peers in standardized measures of clinical aptitude. They demonstrated statistically significant greater preservation of patient-centered attitudes compared with declining values for TC students. Pilot students rated the atmosphere of learning, effective integration of basic and clinical sciences, mentorship, feedback, clerkship satisfaction, and end-of-year patient-care preparedness significantly higher than TC students. The authors conclude that implementation of a longitudinal third-year curriculum, with only modest alterations in existing clinical training frameworks, is feasible and effective in meeting its stated goals. “Exposing” the hidden curriculum through specific longitudinal activities may prevent degradation of student attitudes about patient-centered care. Minimizing the disjointed nature of clinical training during a critical time in students’ training by providing a cohesive longitudinal curriculum in parallel to clinical clerkships, led by faculty with consistent contact with students, can have positive effects on both professional performance and satisfaction.
Novel 5-hydroxytryptamine Receptor 2 B ( 5-HT 2 B ) Receptor Antagonist , Reduces Monocrotaline-induced Pulmonary Arterial Hypertension and Right Ventricular Hypertrophy in Rats

221 words Introduction: 659 words Discussion: 1232 words Abbreviations 5-HT 5-hydroxytryptamine AE alveolar edema AMI alveolar macrophage infiltration DF dexfenfluramine ECG electrocardiogram EDTA ethylenediaminetetraacetic acid FOV field of view iPAH idiopathic pulmonary arterial hypertension LVP left ventricular pressure LVSB left ventricular septal bowing MAP mean arterial pressure MAPK mitogen-activated protein kinase MCT Monocrotaline OLP overall lung pathology PA pulmonary artery PAH pulmonary arterial hypertension PAP peak pulmonary artery pressures PASMC pulmonary arterial smooth muscle cell PBS phosphate buffered saline PE perivascular edema RVP right ventricular pressure RVSP right ventricular systolic pressure This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on April 29, 2010 as DOI: 10.1124/jpet.109. 165001 at A PE T Jornals on N ovem er 3, 2017 jpet.asjournals. org D ow nladed from
Analytical Performance of Amplify-and-Forward MIMO Relaying with Orthogonal Space-Time Block Codes

This paper considers orthogonal space-time block coded transmission for a multiple-input multiple-output channel (MIMO) with non-coherent amplify-and-forward (AF) relaying in Rayleigh fading. We first characterize the statistical properties of the instantaneous signal-to-noise ratio (SNR) at the destination, by deriving new exact closed form expressions for the moment generating function, cumulants, and first and second moments. These results show a reciprocity relationship between the number of antennas at the relay and destination. The probability density function and cumulative distribution function of the SNR are also derived for certain system configurations, and for various asymptotic regimes. We then investigate the system performance by presenting new analytical expressions for the symbol error rate, outage probability, amount of fading, as well as the diversity order and array gain. Our results indicate that the proposed scheme can achieve the maximum diversity order of the non-coherent AF MIMO relay channel.
Evaluating Prognostic Accuracy of Biomarkers under Competing Risk

Summary To develop more targeted intervention strategies, an important research goal is to identify markers predictive of clinical events. A crucial step toward this goal is to characterize the clinical performance of a marker for predicting different types of events. In this article, we present statistical methods for evaluating the performance of a prognostic marker in predicting multiple competing events. To capture the potential time‐varying predictive performance of the marker and incorporate competing risks, we define time‐ and cause‐specific accuracy summaries by stratifying cases based on causes of failure. Such definition would allow one to evaluate the predictive accuracy of a marker for each type of event and compare its predictiveness across event types. Extending the nonparametric crude cause‐specific receiver operating characteristics curve estimators by Saha and Heagerty (2010) , we develop inference procedures for a range of cause‐specific accuracy summaries. To estimate the accuracy measures and assess how covariates may affect the accuracy of a marker under the competing risk setting, we consider two forms of semiparametric models through the cause‐specific hazard framework. These approaches enable a flexible modeling of the relationships between the marker and failure times for each cause, while efficiently accommodating additional covariates. We investigate the asymptotic property of the proposed accuracy estimators and demonstrate the finite sample performance of these estimators through simulation studies. The proposed procedures are illustrated with data from a prostate cancer prognostic study.
Fault Diagnosis of High-Resistance Connection in a Nine-Phase Flux-Switching Permanent-Magnet Machine Considering the Neutral-Point Connection Model

This paper presents a fault diagnosis technique for high-resistance connection (HRC) in a nine-phase flux-switching permanent-magnet (FSPM) machine based on zero-sequence voltage components (ZSVC), where the neutral-point connection mode is considered. A nine-phase FSPM machine topology is first introduced and no-load back electromotive force waveforms are analyzed. Moreover, the topologies of the nine-phase FSPM drive with different neutral-point connection modes are studied. Then, the mathematical model of a nine-phase FSPM machine with HRC is established with the consideration of the neutral-point connection mode and then the influence of the HRC on the ZSVC is analyzed based on the established model. It is shown that the HRC may be diagnosed by monitoring the change of the spectral contents of the ZSVC. Furthermore, this paper focuses on the situation of the nine-phase FSPM machine with one neutral point. In this case, to remove the influence of the FSPM machine operating point, an effective fault indicator is defined and used for HRC fault detection. Finally, the simulation and the experiment are carried out to validate the proposed method. Both the results show that the proposed method can be applied for the HRC fault diagnosis in a nine-phase FSPM machine.
A quantitative analysis of local anaesthetic alteration of miniature end‐plate currents and end‐plate current fluctuations.

1. The effect of the local anaesthetic QX222 on the kinetics of miniature end‐plate currents (m.e.p.c.s) and acetylcholine (ACh) induced end‐plate current (e.p.c) fluctuations was studied in voltage‐clamped frog cutaneous pectoris neuromuscular junctions made visible with Nomarski differential interference contrast optics. 2. In Ringer solution the m.e.p.c. s decayed with a single exponential time course and the e.p.c. fluctuation spectra were characterized by single Lorentzian functions, with the spectral cut‐off frequency well predicted by the m.e.p.c. decay rate. 3. In the presence of 0‐1‐0‐5 mm QX222 at‐50 to ‐100 mV holding potential both the e.p.c. fluctuation spectrum and the m.e.p.c. decay consisted of a fast and a slow component, with the cut‐off frequency of each spectral component predicted by the decay rate of the corresponding constituent of the m.e.p.c. 4. Hyperpolarization increased the decay rate and relative amplitude of the fast component of the m.e.p.c. and decreased the decay rate of the slow m.e.p.c. component. 5. With 0‐05 mm QX222 and ‐70 mV holding potential the m.e.p.c. s. and e.p.c. fluctuation spectra consisted of three components. The third component of the m.e.p.c. and e.p.c. spectra had nearly the same decay rate and cut‐off frequency as was found at the same end‐plate under equivalent conditions before drug exposure. 6. The kinetic predictions of four different schemes for local anaesthetic action were compared with observed m.e.p.c. s. and e.p.c. fluctuations. 7. Schemes in which the local anaesthetic acted by creating two kinetically distinct populations of acetylcholine receptors or by interacting with ACh receptor to produce a biphasic exponential decay of the end‐plate channel conductance did not accurately predict the e.p.c. fluctuation spectrum. 8. The variance of the e.p.c. fluctuations vanished at the reversal potential indicating that local anaesthetic action was not due to the presence of different ion selective end‐plate channels. 9. QX222 action could be explained by alteration of the ACh receptors such that they sequentially c‐hanged from one conductance state to another. A specific case in which QX222 binds to the ACh receptors in its open state creating a partially blocked state, was found to be the most parisimonious. 10. The conductance, gamma, of a single end‐plate channel was estimated from e.p.c. fluctuations. In Ringer's solution gama = 24‐4 +/‐ 1‐2 (s.d.) pmho. In the presence of 0‐1 mm to 0‐5 mm QX222 the effective single channel conductance, gamma, varied from 14‐2 to 1‐39 pmho. 11. gamma decreased with increased local anesthetic concentration, hyperpolarization, or decreased temperature. The variation in gamma is thought to reflect the dependence on the experimental conditions of the relative probability that the ACh receptors is in an open vs a partially blocked state.
Crowdsourcing for bioinformatics

MOTIVATION Bioinformatics is faced with a variety of problems that require human involvement. Tasks like genome annotation, image analysis, knowledge-base population and protein structure determination all benefit from human input. In some cases, people are needed in vast quantities, whereas in others, we need just a few with rare abilities. Crowdsourcing encompasses an emerging collection of approaches for harnessing such distributed human intelligence. Recently, the bioinformatics community has begun to apply crowdsourcing in a variety of contexts, yet few resources are available that describe how these human-powered systems work and how to use them effectively in scientific domains. RESULTS Here, we provide a framework for understanding and applying several different types of crowdsourcing. The framework considers two broad classes: systems for solving large-volume 'microtasks' and systems for solving high-difficulty 'megatasks'. Within these classes, we discuss system types, including volunteer labor, games with a purpose, microtask markets and open innovation contests. We illustrate each system type with successful examples in bioinformatics and conclude with a guide for matching problems to crowdsourcing solutions that highlights the positives and negatives of different approaches.