Miracle-dz/UniFAR-FTUs huggingface dataset:
Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint

Sorafenib is a multikinase inhibitor approved as the first line treatment for late stage hepatocellular carcinoma (HCC). Due to its significant variation in clinical benefits among patients, defining prognostic biomarkers for sorafenib sensitivity in HCC would allow targeted treatment. Phosphorylated extracellular signaling-regulated kinase (pERK) was proposed to predict the response to sorafenib in HCC, but clinical supports are mixed or even contradictory. Here we found that pERK expression levels are variable in different nodules from individual patient liver. Xenografts derived from resected tumors are resistant to sorafenib inhibition when expressing low levels of pERK. This correlation of low pERK levels and sorafenib resistance is corroborated by histological characterization of chemical-induced and genetic mouse models for pERK-positive and pERK-negative HCC respectively, as well as computed tomography (CT) imaging of patient tumors with validated pERK expression. Mouse and human HCC samples expressing low pERK show strong inflammatory infiltrating cells and significant enrichment of intratumoral CD8+ cytotoxic T lymphocytes that express programmed death receptor-1 (PD-1). These pERK−PD-1+ patients have poorer overall and disease-free survival than pERK+PD-1− patients. In conclusion, our data suggest that anti-PD-1 immunotherapy might complement sorafenib in treating HCC patients by targeting sorafenib-resistant cancer cells, and the dual pERK and PD-1 biomarkers would help HCC patient selection to achieve optimal clinical benefits.
Using unitization as encoding strategy in associative recognition memory : behavioral, fMRI, and ERP evidence

Recognition memory is thought to depend on two processes. Whereas familiarity refers to a simple feeling of knowing a stimulus, recollection enables us to remember associative information such as the place of a particular episode in which the stimulus has occurred. Accordingly, recollection, which relies on the integrity of the hippocampus, is generally required to remember arbitrary associations. In contrast, a familiarity signal, presumably arising in the perirhinal cortex, is sufficient to recognize single items. However, it was shown that the integration of separate items into a single configuration (unitization) leads to reduced involvement of recollection and greater reliance on familiarity. Of special interest is the formation of novel units from previously arbitrary associations during a single encoding episode as this accomplishes the unique ability of episodic memory to remember associative information that relates to a specific event. This thesis reports four experiments in which retrieval processes for novel units were compared to those involved for arbitrary associations, pre-existing units and single items. Experiment 1 and 2 revealed behavioral and fMRI evidence that retrieval of arbitrary word pairs involves flexible recollection whereas retrieval processes relied on the exact configuration when word pairs were studied as novel conceptual units (e.g., vegetable bible = a book consulted by hobby gardeners). Hippocampal engagement during retrieval of novel units was reduced in contrast to arbitrary word pairs. Moreover, brain regions specific to the retrieval of novel units and single items were dissociated. Experiment 3 could not replicate previously reported familiarity-related ERP effects for novel conceptual units as well as pre-existing units (e.g., tea cup). Contextual factors influencing familiarity-based retrieval are discussed. The results from Experiment 4 provide preliminary evidence that arranging two unrelated objects as a scene can enhance familiarity for associations suggesting that not only contiguous entities can be perceived as units.
A gene-based map of the Nod factor-independent Aeschynomene evenia sheds new light on the evolution of nodulation and legume genomes

Aeschynomene evenia has emerged as a new model legume for the deciphering of the molecular mechanisms of an alternative symbiotic process that is independent of the Nod factors. Whereas most of the research on nitrogen-fixing symbiosis, legume genetics and genomics has so far focused on Galegoid and Phaseolid legumes, A. evenia falls in the more basal and understudied Dalbergioid clade along with peanut (Arachis hypogaea). To provide insights into the symbiotic genes content and the structure of the A. evenia genome, we established a gene-based genetic map for this species. Firstly, an RNAseq analysis was performed on the two parental lines selected to generate a F2 mapping population. The transcriptomic data were used to develop molecular markers and they allowed the identification of most symbiotic genes. The resulting map comprised 364 markers arranged in 10 linkage groups (2n = 20). A comparative analysis with the sequenced genomes of Arachis duranensis and A. ipaensis, the diploid ancestors of peanut, indicated blocks of conserved macrosynteny. Altogether, these results provided important clues regarding the evolution of symbiotic genes in a Nod factor-independent context. They provide a basis for a genome sequencing project and pave the way for forward genetic analysis of symbiosis in A. evenia.
Maximum Rate of Pressure Development and Maximal Relaxation Rate of Respiratory Muscles in Patients with Cystic Fibrosis

BACKGROUND: Respiratory muscle function in patients with cystic fibrosis (CF) has been studied by measurement of maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). The maximum rate of pressure development (MRPD) during PImax (MRPD-PImax), MRPD during PEmax (MRPD-PEmax), maximal relaxation rate (MRR) during PImax (MRR-PImax), and MRR during PEmax (MRR-PEmax) have not been studied in CF. Our aim was to study MRPD and MRR and investigate their possible application as accessory indices of respiratory muscle function in patients with CF. METHODS: FEV1, FVC, and maximal expiratory flow between 25% and 75% of vital capacity, body mass index (BMI), upper arm muscle area, PImax, PEmax, PTImus, MRPD-PImax, MRPD-PEmax, MRR-PImax, and MRR-PEmax were assessed in 123 CF patients and in a control group of 123 healthy subjects matched for age and sex. RESULTS: MRR-PEmax was significantly increased and MRPD-PEmax was significantly decreased in the CF patients, compared to the healthy controls. In the CF patients MRR-PImax was significantly related to PTImus (P = .02), FEV1 (P = .03), FVC (P = .001), BMI (P < .001), and upper arm muscle area (P < .001). In the CF patients, MRPD-PImax and MRPD-PEmax were significantly related to upper arm muscle area (P < .001), BMI (P < .001 and P = .01, respectively), PImax (P < .001), and PEmax (P < .001). CONCLUSIONS: The CF patients exhibited increased MRR and decreased MRPD during maximal respiratory effort, compared to controls. The differences in MRR-PImax and MRPD-PImax between the controls and the complete group of CF patients were not significant. MRPD and MRR were significantly related to nutritional and pulmonary function impairment in CF patients. MRPD strongly correlated to maximal respiratory muscle pressures, and MRR strongly correlated to PTImus in patients with CF. These findings suggest that CF patients are at increased risk of respiratory muscle fatigue. Regular determination of MRPD and MRR may be clinically useful in CF patients and help to initiate inspiratory muscle training and noninvasive ventilation.
Turkish Version of Self Concept and Identity Measure (SCIM): Psychometric Properties

111 Abstract In the current study, it is aimed to adapt Self-Concept and Identity Measure (SCIM) into Turkish. The participants of the study were internet users (n = 364). According to exploratory factor analysis results, Turkish version of SCIM (T-SCIM) consists of two factors (disturbed identity and consolidated identity). Moreover, T-SCIM showed expected correlations with emotion regulation, coping strategies, and psychopathologies. The internal consistency (Cronbach’s α = 0.88) and test-retest reliability (α = 0.82, r = 0.70; ICC = 0.82) scores were found to be very good. It is concluded that T-SCIM is a reliable and valid scale that can be used in Turkey. (Journal of Cognitive Behavioral Psychotherapy and Research 2016; 111-118)
Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers

Aptamers directed against human thrombin can selectively bind to two different exosites on the protein surface. The simultaneous use of two DNA aptamers, HD1 and HD22, directed to exosite I and exosite II respectively, is a very powerful approach to exploit their combined affinity. Indeed, strategies to link HD1 and HD22 together have been proposed in order to create a single bivalent molecule with an enhanced ability to control thrombin activity. In this work, the crystal structures of two ternary complexes, in which thrombin is sandwiched between two DNA aptamers, are presented and discussed. The structures shed light on the cross talk between the two exosites. The through-bond effects are particularly evident at exosite II, with net consequences on the HD22 structure. Moreover, thermodynamic data on the binding of the two aptamers are also reported and analyzed.
A High-Level Petri Net Framework for Genetic Regulatory Networks

Summary To understand the function of genetic regulatory networks in the development of cellular systems, we must not only realise the individual network entities, but also the manner by which they interact. Multi-valued networks are a promising qualitative approach for modelling such genetic regulatory networks, however, at present they have limited formal analysis techniques and tools. We present a flexible formal framework for modelling and analysing multi-valued genetic regulatory networks using high-level Petri nets and logic minimization techniques. We demonstrate our approach with a detailed case study in which part of the genetic regulatory network responsible for the carbon starvation stress response in Escherichia coli is modelled and analysed. We then compare and contrast this multivalued model to a corresponding Boolean model and consider their formal relationship.
New dynamic programming algorithms for the resource constrained elementary shortest path problem

The resource constrained elementary shortest path problem (RCESPP) arises as a pricing subproblem in branch‐and‐price algorithms for vehicle‐routing problems with additional constraints. We address the optimization of the RCESPP and we present and compare three methods. The first method is a well‐known exact dynamic‐programming algorithm improved by new ideas, such as bidirectional search with resource‐based bounding. The second method consists in a branch‐and‐bound algorithm, where lower bounds are computed by dynamic‐programming with state‐space relaxation; we show how bounded bidirectional search can be adapted to state‐space relaxation and we present different branching strategies and their hybridization. The third method, called decremental state‐space relaxation, is a new one; exact dynamic‐programming and state‐space relaxation are two special cases of this new method. The experimental comparison of the three methods is definitely favorable to decrement state‐space relaxation. Computational results are given for different kinds of resources, arising from the capacitated vehicle‐routing problem, the vehicle‐routing problem with distribution and collection, and the vehicle‐routing problem with capacities and time windows. © 2007 Wiley Periodicals, Inc. NETWORKS, 2008
The value of a family history of sudden death in patients with diagnostic type I Brugada ECG pattern.

AIMS We sought to investigate the value of a family history of sudden death (SD) in Brugada syndrome (BS). METHODS AND RESULTS Two hundred and eighty consecutive patients (mean age: 41 ± 18 years, 168 males) with diagnostic type I Brugada ECG pattern were included. Sudden death occurred in 69 (43%) of 157 families. One hundred and ten SDs were analysed. During follow-up VF (ventricular fibrillation) or SD-free survival rate was not different between patients with or without a family history of SD of a first-degree relative, between patients with or without a family history of multiple SD of a first-degree relative at any age and between patients with or without a family history of SD in first-degree relatives ≤35 years. One patient had family history of SD of two first-degree relative ≤35 years with arrhythmic event during follow-up. In univariate analysis male gender (P = 0.01), aborted SD (P < 0.001), syncope (P = 0.04), spontaneous type I ECG (P < 0.001), and inducibility during electrophysiological (EP) study (P < 0.001) were associated with worse prognosis. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study was associated with a significantly better prognosis (P < 0.001). CONCLUSION Family history of SD is not predictive for future arrhythmic events even if considering only SD in first-degree relatives or SD in first-degree relatives at a young age. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study is associated with a good five-year prognosis.
Hybrid Task Planning Grounded in Belief: Constructing Physical Copies of Simple Structures

Symbolic planning methods have proved to be challenging in robotics due to partial observability and noise as well as unavoidable exceptions to rules that symbol semantics depend on. Often the symbols that a robot considers to support for planning are brittle, making them unsuited for even relatively short term use. Maturing probabilistic methods in robotics, however, are providing a sound basis for symbol grounding that supports using probabilistic distributions over symbolic entities as the basis for planning. In this paper, we describe a belief-space planner that stabilizes the semantics of feedback from the environment by actively interacting with a scene. When distributions over higher-level abstractions stabilize, powerful symbolic planning techniques can provide reliable guidance for problem solving. We present such an approach in a hybrid planning scheme that actively controls uncertainty and yields robust state estimation with bounds on uncertainty that can make effective use of powerful symbolic planning techniques. We illustrate the idea in a hybrid planner for autonomous construction tasks with a real robot system.
Processing of Chemical Sensor Arrays with a Biologically Inspired Model of Olfactory Coding

This paper presents a computational model for chemical sensor arrays inspired by the first two stages in the olfactory pathway: distributed coding with olfactory receptor neurons and chemotopic convergence onto glomerular units. We propose a monotonic concentration-response model that maps conventional sensor-array inputs into a distributed activation pattern across a large population of neuroreceptors. Projection onto glomerular units in the olfactory bulb is then simulated with a self-organizing model of chemotopic convergence. The pattern recognition performance of the model is characterized using a database of odor patterns from an array of temperature modulated chemical sensors. The chemotopic code achieved by the proposed model is shown to improve the signal-to-noise ratio available at the sensor inputs while being consistent with results from neurobiology.
Reduced risk of surgical site infections through surveillance in a network.

OBJECTIVE To estimate the effect of multicentre surveillance for nosocomial infections on patients' risk of surgical site infection (SSI). DESIGN Prospective multi-centre cohort study, from January 1996 to December 2000. SETTING Acute care hospitals in The Netherlands. STUDY PARTICIPANTS All 50 hospitals performing surveillance for one of seven selected procedures in the Dutch surveillance network for nosocomial infections PREZIES were invited. Thirty-seven hospitals participated (74%) and provided information on 21 920 operations, after which 885 (4%) SSI occurred. INTERVENTIONS The surveillance comprised the following: Development of surveillance methodology by multidisciplinary team; use of a standardized registration protocol and software; regular training of data collectors; anonymous inter-hospital comparison of infection rates and feedback of results; appointment of one contact person per hospital, responsible for data collection; and dissemination of results to other health care professionals. Regular discussion of both successful and failing prevention strategies that had been instituted based on the surveillance results. OUTCOME MEASURE Risk of SSI. RESULTS The risk of infection was reduced for patients who had an operation during the fourth surveillance year (RR = 0.69; 95% confidence interval (CI) = 0.52-0.89) and decreased further for patients operated on during the fifth surveillance year (RR = 0.43; CI = 0.24-0.76) as compared with patients who underwent surgery within one year of the start of surveillance in their hospital. No significant risk reduction was observed for patients operated on during the second and third surveillance years. CONCLUSION Surveillance, supported by participation in a surveillance network, reduced the risk of SSI in surgical patients registered in the Dutch surveillance network PREZIES. Our results suggest that infection control teams need to be perseverant and that surveillance programmes should be given time before evaluation.
Cytotoxic T Lymphocytes Protein 70 Overexpression in Tumor Cells on Lysability by Differential Effect of Acute and Permanent Heat Shock

We have shown previously that acute heat shock protein (Hsp) 70 induction in a human melanoma cell line containing a doxycyclineinducible Hsp70 expression construct increases lysability of these tumor cells by cytotoxic T lymphocyte (CTL) without interfering with MHC class I expression and antigen presentation. The same parental melanoma cell line has now been transduced retrovirally to overexpress Hsp70 permanently. Here we demonstrate that MHC class I cell surface expression is again not altered and that these cells, in contrast with acutely Hsp70 overexpressing cells, do not show augmentation of CTL-mediated apoptosis. Also, long-term induction of Hsp70 in cells with the doxycycline-inducible Hsp70 construct leads to abrogation of increased lysability. Because, furthermore, after heat shock the same permanently Hsp70 overexpressing cells show Hsp70 induction and increased lysability, it is hypothesized that acutely available Hsp70 is able to chaperone proteins that are involved in CTL-mediated apoptosis of target cells and to thereby improve their lysability. We also observed that permanent but not acute Hsp70 overexpression resulted in decreased levels of Hsc70, the constitutively expressed member of the Hsp70 family. Down-regulation of Hsc70 occurs at the post-transcriptional level and can be observed also after long-term induction of Hsp70 in cells containing the doxycycline-inducible expression system. Hsc70 down-regulation might reflect a functional integration of the overexpressed Hsp70 on the basis of a chaperone network so that only acute induction will provide Hsp70 that can improve tumor cell lysability. The implications of the differential effect of acute versus permanent Hsp70 overexpression for tumor therapy are discussed.
Please stop rubbing your relationship in my Face(book): An investigation of online romantic social comparison.

ii Acknowledgements . iii List of Tables . vi List of Figures . vii Chapter 1: Introduction . 1 Social Media and Social Comparison . 1 Social Media and Romantic Relationships . 3 The Present Study: Romantic Social Comparison on Social Media . 5 Attachment orientation . 6 Relationship-contingent self-esteem . 7 Fear of being single . 7 Tendency to engage in social comparison . 8 Trait self-esteem . 9 Summary of Hypotheses . 9 Chapter 2: Study One . 12 Participants . 13 Procedure and Measures . 14 Prescreening measures . 14 Ethics. 16 Manipulation of pessimism for future relationships . 16 Social comparison condition (photographs). 17 In-lab questionnaires . 18 Results . 19 Data analytic strategy . 19 Preliminary analyses . 21 Correlation analyses . 23 Impact of viewing romantic content on state self-esteem . 24 Impact of viewing romantic content on affect . 31 Impressions of and attitudes towards object of comparison . 34 Discussion . 40 Chapter 3: Study Two . 44 Participants . 45 v Procedure and Measures . 45 Prescreening measures . 45 Ethics. 46 Rejection threat manipulation . 46 Social comparison condition (photographs). 48 In-lab questionnaires . 48 Results . 49 Data analytic strategy . 49 Preliminary analyses . 50 Correlation analyses . 52 Impact of viewing romantic content on state self-esteem . 54 Impact of viewing romantic content on affect . 55 Impact of viewing romantic content on relationship satisfaction . 58 Impressions of and attitudes towards object of comparison . 58 Exploratory post-hoc correlation analyses . 61 Discussion . 70 Chapter 4: General Discussion . 76 Summary of Findings . 77 Single individuals and online romantic social comparison . 77 Dating individuals and online romantic social comparison . 79 Limitations and Future Directions . 80 Implications. 84 References . 86 Appendix A: Ethics Documents . 95 Appendix B: Prescreening Measures . 100 Appendix C: Study Two (Rejection Threat Manipulation) . 103 Appendix D: In-Lab Questionnaires . 105 Appendix E: Bivariate Correlations By Group (Study One) . 108 Appendix F: Bivariate Correlations By Group (Study Two) . 111 Appendix G: Pilot Study (Background and Preliminary Data) . 115
Tele-guidance to develop reflective practice: experiences in four teacher education programmes across Europe

Abstract The use of tele-guidance environments with student teachers and their teacher educators was implemented during teaching practice and evaluated for four European teacher education programmes in the REFLECT project. Tele-guidance can be contrasted with more common supervision methods such as face-to-face meetings between the student teachers and the participating teacher, or between a group of student teachers and their supervisors at the teacher education institution. In our research and evaluation, we focused on the content and the nature of discourse in different modes of tele-guidance in teacher education, particularly with respect to student teachers' reflective practice. During their field experiences, tele-guidance was primarily used by student teachers for reflection on technical and practical issues. It was used less than expected for critical reflection and exchanging pedagogical content knowledge, including general and instructional theories, and aspects of the teaching profession. The r.
Ambient inspections in environmental enforcement: an extension

We consider an inspection game between an arbitrary number of polluting firms and an agency who can choose to monitor ambient pollution. We obtain an equilibrium where all firms comply with the same probability and where the inspection agency inspects all firms individually if ambient pollution exceeds an endogenous threshold. If the fine for noncompliance is high enough, the agency's costs are lower then if it does not monitor ambient pollution. If the firms believe the agency's announcement that it conducts ambient inspections, their probability of compliance can be so high that the agency will want to deviate.