Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro Toxicity Testing in the Twenty-First Century

The National Research Council (NRC) article “Toxicity Testing in the 21st Century: A vision and A Strategy” (National Research Council, 2007) was written to bring attention to the application of scientific advances for use in toxicity tests so that chemicals can be tested in a more time and cost efficient manner while providing a more relevant and mechanistic insight into the toxic potential of a compound. Development of tools for in vitro toxicity testing constitutes an important activity of this vision and contributes to the provision of test systems as well as data that are essential for the development of computer modeling tools for, e.g., system biology, physiologically based modeling. This article intends to highlight some of the issues that have to be addressed in order to make in vitro toxicity testing a reality in the twenty-first century.
Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy

Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HMEC-1). The sensitivity of HMEC-1 cells to a 5 min treatment by electroporation with bleomycin or cisplatin (8 electric pulses, pulse duration 100 μs, frequency 1 Hz, electric field intensity 1400 V cm−1) was compared to the sensitivity of cells treated continuously for 3 days with drugs alone. HMEC-1 cells were moderately sensitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses increased cytotoxicity of cisplatin by ∼10-fold for cisplatin and ∼5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 min exposure was ∼250-fold better than a continuous exposure to the drug alone. The results of this study indicate that the anti-tumour action of electrochemotherapy is likely to be due, in part, to the highly sensitive response of vascular endothelial cells. Further studies are necessary to identify the determinants of endothelial response and its relationship to the anti-vascular action of electrochemotherapy in vivo. © 2001 Cancer Research Campaign
[Neuropsychiatric Inventory-Nursing Home version (NPI-NH): Spanish validation].

INTRODUCTION The Neuropsychiatric Inventory-Nursing Home version (NPI-NH) is a screening instrument to be used by the nursing staff to evaluate neuropsychiatric symptoms in dementia patients in the nursing home setting. The aim of the present study was to validate the NPI-NH in Spanish. METHODS We assessed the validity of the NPI-NH in 80 patients who were also nursing home residents, comparing the responses of nursing home staff on the NPI-NH with that filled out by the external observer. We developed a crossed validated form between the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and both NPI-NH. We determined the concurrent validity of the domains "depression" and "agitation/aggression" of the NPI-NH with the Cohen-Mansfield Agitation Inventory (IAACM, Spanish version) and the Hamilton Depression Rating Scale (HDRS). RESULTS Among the totals of the NPI-NH of the nursing staff and the NPI-Q, the convergent validity was r = 0.536 and r = 0.669 for the occupational disruptiveness scale (distress in NPI-Q). The Pearson correlation index between the NPI-Q and NPI-NH of the observations was r = 0.342. The convergent validity between the NPINH of the nursing home staff and NPI-NH of the observers with the Pearson correlation index was r = 0.274. CONCLUSIONS The NPI-NH Spanish version offers the possibility to use a screening tool for detecting neuropsychiatric symptoms in dementia patients in the nursing home setting. It should be administered by adequately trained staff to avoid limitations in the evolutive control of behavioral changes.
Clustering and dimensionality reduction for image retrieval in high-dimensional spaces

The scalability of indexing techniques and image retrieval pose many problems. Indeed, their performance degrades rapidly when the database size increases. In this paper, we propose an efficient indexing method for high-dimensional spaces. We investigate how high-dimensional indexing methods can be used on a partitioned space into clusters to help the design of an efficient and robust CBIR scheme. We develop a new method for efficient clustering is used for structuring objects in the feature space; this method allows dividing the base into data groups according to their similarity, in function of the parameter thresh- old and vocabulary size. A comparative study is presented between the proposed method and a set of classification methods. The experiments results on the Pascal Visual Object Classes challenges (VOC) of 2007 and Caltech-256 dataset show that our method signifi- cantly improves the performance. Experimental retrieval results based on the preci- sion/recall measures show interesting results.
Temperature dependence of predation depends on the relative performance of predators and prey

The temperature dependence of predation rates is a key issue for understanding and predicting the responses of ecosystems to climate change. Using a simple mechanistic model, we demonstrate that differences in the relative performances of predator and prey can cause strong threshold effects in the temperature dependence of attack rates. Empirical data on the attack rate of northern pike (Esox lucius) feeding on brown trout (Salmo trutta) confirm this result. Attack rates fell sharply below a threshold temperature of +11°C, which corresponded to a shift in relative performance of pike and brown trout with respect to maximum attack and escape swimming speeds. The average attack speed of pike was an order of magnitude lower than the escape speed of brown trout at 5°C, but approximately equal at temperatures above 11°C. Thresholds in the temperature dependence of ecological rates can create tipping points in the responses of ecosystems to increasing temperatures. Thus, identifying thresholds is crucial when predicting future effects of climate warming.
Experimental Evaluation of an Angle Based Indoor Localization System

In this paper, we present an experimental prototype of an indoor localization system that uses angle estimation and decentralized computations. The system uses three rotating optical beacon signal generators that are built using commonly available off-the-shelf components. Wireless sensor nodes equipped with photo sensors determine their locations from the estimated angular separations between the optical sources. No additional hardware is required at the sensor nodes. The system also does not involve any centralized server or off-line measurements, which are key requirements of RF-based localization systems. We present the design principles, possible sources of error, and the lessons learnt from building the experimental localization system. Performance results obtained from laboratory experiments are presented. The proposed system provides location estimates that are accurate within a few inches in indoor applications. In addition, the idea may be extended to large scale outdoor sensor systems where it may not be economically or physically viable to use additional localization hardware such as GPS.
Group Heterogeneity Increases the Risks of Large Group Size

Heterogeneous groups are valuable, but differences among members can weaken group identification. Weak group identification may be especially problematic in larger groups, which, in contrast with smaller groups, require more attention to motivating members and coordinating their tasks. We hypothesized that as groups increase in size, productivity would decrease with greater heterogeneity. We studied the longitudinal productivity of 549 research groups varying in disciplinary heterogeneity, institutional heterogeneity, and size. We examined their publication and citation productivity before their projects started and 5 to 9 years later. Larger groups were more productive than smaller groups, but their marginal productivity declined as their heterogeneity increased, either because their members belonged to more disciplines or to more institutions. These results provide evidence that group heterogeneity moderates the effects of group size, and they suggest that desirable diversity in groups may be better leveraged in smaller, more cohesive units.
Carcinomata developing at the site of foreign bodies in the lung

THIS paper records two cases of carcinoma of the Bronchoscopy. -Carcinoma seen at orifice of middle bronchus occurring at the site of retained metallic lobe bronchus, confirmed by biopsy, August, 1949. foreign bodies. ln both the foreign bodies Dissection Pneumonectomy.A portion of pericardium were war missiles and the patients died of carciinvolved with growth was excised. The post-operative course was stormy and complicated by the early noma 32 and 35 years after injury. In One the appearance of a bronchopleural fistula and empyema diagnosis was not proven histologically. requiring pleural drainage. -October, 1949 : Discharged home in poor condition
HuR and podoplanin expression is associated with a high risk of malignant transformation in patients with oral preneoplastic lesions

The risk of malignant transformation in oral preneoplastic lesions (OPLs) is challenging to assess. The objective of the present study was to determine the expression of ELAV like RNA binding protein 1 (HuR) and podoplanin in OPLs, and to evaluate the use of each protein as biomarkers for the risk assessment of malignant transformations. Immunohistochemistry for HuR and podoplanin was performed on the tissues of 51 patients with OPL, including cases of low grade dysplasia (LGD) and high grade dysplasia (HGD). The association between the protein expression patterns and clinicopathological parameters, including oral cancer free survival (OCFS) time, was analyzed during the follow-up period. HuR and podoplanin expression was observed in 28 (55%) and 36 (71%) of 51 patients, respectively. Kaplan-Meier analysis showed that the expression of HuR and podoplanin was associated with the risk of progression to oral cancer (P<0.05). Multivariate analysis revealed that HuR and podoplanin expression was associated with a 2.93-fold (95% confidence interval (CI), 0.98–10.34; P=0.055) and 2.06-fold (95% CI, 0.55–8.01; P=0.283) increase in risk of malignant transformation, respectively. The risk of OPL malignant transformation was considerably increased with the coexpression of HuR and podoplanin compared with the histological grading (95% CI, 1.64–23.59; P=0.005). The results of the present study demonstrated that the expression of HuR and podoplanin associates with malignant transformation and suggests that the proteins may be used as biomarkers to identify OPL patients with an increased risk of cancer development.
Mental health assessments in juvenile justice: report on the consensus conference.

OBJECTIVE At national, state, and local levels, there is increasing recognition of the importance of identifying and responding to the mental health needs of youths in the juvenile justice system, as policymakers and practitioners struggle to find ways to address causes and correlates of juvenile crime and delinquency. The proposed guidelines for mental health assessment provide explicit information about how, why, and when to obtain mental health information on justice youths at each important juncture in processing. METHOD A national group of expert researchers and practitioners convened in April 2002. Experts derived six recommendations, following the expert consensus method, for conducting mental health assessments in juvenile justice settings. Experts had broad experience creating collaborations between juvenile justice, mental health, and child welfare systems and understood the policy and health implications of conducting such assessments in juvenile justice settings. RESULTS Consensus Conference recommendations regarding screening for emergent risk, screening and assessment of mental health service needs, comprehensive mental health assessment components, assessment before community re-entry, need for periodic reassessment, and staff training are presented. CONCLUSION Deriving specific recommendations that can be implemented systematically is a necessary first step toward policy changes that will optimize the standard of care for this vulnerable population.
Relating reliability to circuit topology

Reliability analysis of nano-scale circuits can be done using different techniques, one of them being Bayesian networks. Using this scheme, the relationship of circuit's topology to reliability has been studied for several thousand randomly generated (combinational) 3 to 9 variable circuits; the circuits contained up to 40 gates in up to 10 tiers/levels. As anticipated, strong, positive correlations were found between gate counts and circuit's probability of failure (PF), and between the level counts and circuit PF. However, the input counts and the circuit PFs were weakly correlated. These findings can be useful in creating reliability models for arbitrary circuits.
Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer cells to tumor necrosis factor α‐induced apoptosis

Overexpression of anti‐apoptosis protein cIAP1 due to its genetic amplification is found in certain cancers such as esophageal squamous cell carcinoma, hepatocellular carcinoma, cervical cancer and lung cancer, and plays a significant role in resistance to cancer therapy. We previously reported that a class of small molecules represented by (−)‐N‐[(2S, 3R)‐3‐amino‐2‐hydroxy‐4‐phenyl‐butyryl]‐L‐leucine methyl ester (MeBS) activates auto‐ubiquitylation of cIAP1 for proteasomal degradation, and enhances apoptosis of various cancer cells. However, the molecular mechanism of how MeBS sensitizes cancer cells to apoptosis via downregulation of cIAP1 is not well understood. Here, we show that ubiquitylation and distribution of RIP1, a protein ubiquitylated by cIAP1, is modulated by MeBS. Upon tumor necrosis factor (TNF)α stimulation, ubiquitylated RIP1 associates with the TNF‐receptor (TNFR) complex, whereas non‐ubiquitylated RIP1 associates with caspase8. MeBS reduces the ubiquitylated RIP1 in the TNFR complex and increases non‐ubiquitylated RIP1 bound to caspase8. Downregulation of RIP1 by siRNA reduces apoptosis induced by TNFα plus MeBS treatment. These results indicate an important role of RIP1 in apoptosis induced by combined treatment with TNFα and MeBS, suggesting that MeBS sensitizes cancer cells to apoptosis by modulating RIP1 ubiquitylation and distribution. (Cancer Sci 2010; 101: 2425–2429)
Susceptible periods during embryogenesis of the heart and endocrine glands.

One of the original principles of teratology states that, "Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence" [Wilson JG. Environment and Birth Defects. New York:Academic Press, 1973]. The time of greatest sensitivity encompasses the period of organ formation during weeks 3-8 following fertilization in human gestation. At this time, stem cell populations for each organ's morphogenesis are established and inductive events for the initiation of differentiation occur. Structural defects of the heart and endocrine system are no exception to this axiom and have their origins during this time frame. Although the function and maturation of these organs may be affected at later stages, structural defects and loss of cell types usually occur during these early phases of development. Thus, to determine critical windows for studying mechanisms of teratogenesis, it is essential to understand the developmental processes that establish these organs. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12
Gaussian Processes for time-marked time-series data

In many settings, data is collected as multiple time series, where each recorded time series is an observation of some underlying dynamical process of interest. These observations are often time-marked with known event times, and one desires to do a range of standard analyses. When there is only one time marker, one simply aligns the observations temporally on that marker. When multiple time-markers are present and are at dierent times on dierent time series observations, these analyses are more dicult. We describe a Gaussian Process model for analyzing multiple time series with multiple time markings, and we test it on a variety of data.
Introduction of a new electronic medical weekend handover at Tunbridge Wells Hospital

Abstract Effective handover between shifts is vital to protect patient safety and assist doctors with clinical governance. Poor quality, or inadequate handover can lead to serious harm for both patients and doctors. The weekend medical handover system among junior doctors at Tunbridge Wells Hospital in Pembury, UK was cumbersome, inadequate and poor, restricting the ability to provide good patient care. 78.6% of doctors felt that the introduction of an electronic weekend handover system would address the issues in order to improve communication between the medical teams and thus improve patient care. A five week trial of an excel based electronic weekend handover system was conducted. 87.5% of the doctors surveyed felt that the new electronic weekend handover was better or significantly better than the old paper based handover system. The effectiveness rating of the weekend medical handover, with 1 (least effective) - 10 (most effective), rose from 6.14 to 7.31 after introduction of the electronic weekend medical handover system. As a result, this project has become part of the junior doctors medical induction, ensuring permanence of electronic weekend medical handover. This project takes a step towards improved patient safety as well improving the working conditions for junior doctors in a busy acute medical unit. There is always a need to refine and optimise systems and though this project is not perfect, it is a step toward electronic handover that is available now and free of cost.
A complement fixation technique for the quantitative measurement of antigenic differences between strains of the virus of foot-and-mouth disease

1. A complement fixation test has been developed to measure the minor antigenic differences which occur between strains of the virus of foot-and-mouth disease of the same immunological type. 2. Strain-specific sera were prepared from each of the virus strains examined and then titrated with each of the antigens. 3. The amounts of complement fixed in each reaction were measured in the region of maximal fixation where the antigen and antibody were present in optimal proportions. 4. Heterologous antigen-antibody reactions were compared with the homologous reaction in each test and expressed as cross-fixation ratios. 5. Pairs of antigens could then be compared by taking the product of their cross-fixation ratios one with the other. The values of cross-fixation product so obtained ranged from 1·0 between identical strains to 0·01 between strains of different immunological type. 6. Strains of virus which exhibit cross-fixation products of 0·5 or more with one another have been classified within subtype groups. I wish to acknowledge the guidance and encouragement of Dr J. B. Brooksby, Director of the Animal Virus Research Institute, Pirbright, and the technical assistance of Mr E. Scoates.
Starch as a major integrator in the regulation of plant growth

Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production.
Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis

We have compiled the p73-mediated cell cycle arrest and apoptosis pathways. p73 is a member of the p53 family, consisting of p53, p63 and p73. p73 exists in several isoforms, presenting different domain structures. p73 functions not only as a tumor suppressor in apoptosis but also as differentiator in embryo development. p53 mutations are responsible for half of the human cancers; p73 can partially substitute mutant p53 as tumor suppressor. The pathways we assembled create a p73-centered network consisting of 53 proteins and 176 interactions. We clustered our network into five functional categories: Upregulation, Activation, Suppression, Transcriptional Activity and Degradation. Our literature searches led to discovering proteins (c-Jun and pRb) with apparent opposing functional effects; these indicate either currently missing proteins and interactions or experimental misidentification or functional annotation. For convenience, here we present the p73 network using the molecular interaction map (MIM) notation. The p73 MIM is unique amongst MIMs, since it further implements detailed domain features. We highlight shared pathways between p53 and p73. We expect that the compiled and organized network would be useful to p53 family-based studies.
Encoding Monomorphic and Polymorphic Types

Most automatic theorem provers are restricted to untyped logics, and existing translations from typed logics are bulky or unsound. Recent research proposes monotonicity as a means to remove some clutter. Here we pursue this approach systematically, analysing formally a variety of encodings that further improve on efficiency while retaining soundness and completeness. We extend the approach to rank-1 polymorphism and present alternative schemes that lighten the translation of polymorphic symbols based on the novel notion of "cover". The new encodings are implemented, and partly proved correct, in Isabelle/HOL. Our evaluation finds them vastly superior to previous schemes.