Miracle-dz/UniFAR-FTUs huggingface dataset:
p53 Elevation in Relation to Levels and Cytotoxicity of Mono- and Bifunctional Melphalan-DNA Adducts

We tested the hypothesis that bifunctional DNA adducts formed by a nitrogen mustard-based anticancer drug were more efficient than monofunctional adducts at causing elevation of p53, consistent with the difference in cytotoxicity. Human leukemia cell line ML-1 was exposed for 1 h to melphalan or its monofunctional derivative monohydroxymelphalan. Levels of DNA adducts, measured by specific immunoassay, were linearly related to the concentration of alkylating agent. Monohydroxymelphalan formed twice as many adducts as did equal concentrations of melphalan. After the removal of the alkylating agent, adduct levels were maintained or increased slightly up to 8 h and then decreased by 27 to 44% by 24 h. Alkaline elution analyses confirmed the absence of detectable DNA interstrand cross-links in cells exposed to monohydroxymelphalan. DNA single-strand breaks were detected after monohydroxymelphalan but not after melphalan. Levels of p53 were quantified by sensitive fluorogenic enzyme-linked immunosorbent assay at intervals up to 24 h after exposure of cells to various concentrations of melphalan and monohydroxymelphalan. The level of initially formed DNA adducts needed to cause elevation of p53 from a baseline level of 0.5 ng/mg total protein to 2 ng/mg was 5- to 8-fold higher for monohydroxymelphalan than melphalan. The concentrations of melphalan and monohydroxymelphalan (±S.D.) causing 50% growth inhibition were 1.2 ± 0.4 and 28.1 ± 1.6 μg/ml, respectively, a 23-fold difference. The adduct levels induced by these exposures were 9.3 and 420 nmol/g DNA for melphalan and monohydroxymelphalan, respectively, a 45-fold difference, which is considerably greater than the difference in efficacy at elevating p53.
Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation

The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to the control of cell death processes but the molecular details remain to be characterized. One important aspect of fully understanding this pathway is the biochemical description of the hypusine modification system. Here we have used recombinant eIF5A proteins either modified by hypusination or non-modified to establish a bi-dimensional electrophoresis (2D-E) profile for the three eIF5A protein isoforms and their hypusinated or unmodified proteoforms present in Arabidopsis thaliana. The combined use of the recombinant 2D-E profile together with 2D-E/western blot analysis from whole plant extracts has provided a quantitative approach to measure the hypusination status of eIF5A. We have used this information to demonstrate that treatment with the hormone abscisic acid produces an alteration of the hypusine modification system in Arabidopsis thaliana. Overall this study presents the first biochemical description of the post-translational modification of eIF5A by hypusination which will be functionally relevant for future studies related to the characterization of this pathway in Arabidopsis thaliana.
Effectiveness Evaluation of Rule Based Classifiers for the Classification of Iris Data Set

In machine learning, classification refers to a step by step procedure for designating a given piece of input data into any one of the given categories. There are many classification problem occurs and need to be solved. Different types are classification algorithms like tree-based, rule-based, etc are widely used. This work studies the effectiveness of Rule-Based classifiers for classification by taking a sample data set from UCI machine learning repository using the open source machine learning tool. A comparison of different rule- based classifiers used in Data Mining and a practical guideline for selecting the most suited algorithm for a classification is presented and some empirical criteria for describing and evaluating the classifiers are given.
Shelf Life and Chemical Stability of Calcium Phosphate Coatings Applied to Poly Carbonate Urethane Substrates

Many modern orthopaedic implants are coated with calcium phosphate to improve the host tissue response to the implants. Despite numerous studies on the dissolution properties of calcium phosphate (CaP) coatings, the coating “shelf life” (i.e. the chemical stability of these coatings prior to implantation), has not been investigated adequately, particularly for CaP coatings applied to polymeric substrates. This paper examines the chemical stability of CaP coatings that were applied to a poly carbonate urethane (PCU) substrate by an aqueous, low temperature technique. Applying a CaP coating to the PCU surface is designed to enhance the fixation between the implant and adjacent vertebrae. High temperature coating techniques are unfeasible for polymeric substrates, like PCU, because the high temperature may critically degrade the substrate. The CaP coating shelf life was assessed by using FTIR-ATR and SEM to analyze changes in CaP-coated PCU discs over time. The expected in vivo chemical stability of the CaP coating was measured by immersing CaP-coated PCU discs in cell culture media under physiological conditions. ICP-OES was used to measure the calcium and phosphorus concentrations of the immersion solution.
Factored MCTS for Large Scale Stochastic Planning

This paper investigates stochastic planning problemswith large factored state and action spaces. We show that even with moderate increase in the size of existing challenge problems, the performance of state of the art algorithms deteriorates rapidly, making them ineffective.To address this problem we propose a family of simple but scalable online planning algorithms that combine sampling, as in Monte Carlo tree search, with “aggregation,” where the aggregation approximates a distribution over random variables by the product of their marginals. The algorithms are correct under some rather strong technical conditions and can serve as an unsound but effective heuristic when the conditions do not hold. An extensive experimental evaluation demonstrates that the new algorithms provide significant improvement over the state of the art when solving largeproblems in a number of challenge benchmark domains.
CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline

Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. SUMMARY: Germ granules in C. elegans are required for fertility and the maintenance of germ cell identity, but also function to repress sperm-specific expression in during oogenesis.
Edaphic and seasonal heterogeneity of seed banks in agricultural fields of a tropical dry forest region in southern Mexico

The slash-and-burn agriculture practiced across tropical dry regions results in the elimination of native vegetation. Upon fi eld abandonment, the seed bank becomes a potentially important mechanism of natural regeneration at early successional stages. Soil properties and climate seasonality may affect seed bank characteristics, thus we analyzed the effects of these two factors on seed bank density and composition in agricultural fi elds of a seasonally dry tropical region of southern Mexico. Soil cores were collected for the rainy and the dry seasons in order to assess changes occurring in the seed bank from the time of harvest to the moment when succession could potentially start (the next rainy season). The 12 studied fi elds comprised three different soil types recognized by local inhabitants: sandy and stony, silty, and clayey soils, locally known as cascajo, black soil, and red soil, respec- tively. At each fi eld 20 soil cores (8 cm diameter, 4.5 cm depth) were collected and mixed to form four pooled samples, which were placed in a greenhouse to induce germination. A total of 4,422 seedlings (2,291 seeds m -2 ) representing 40 species were recorded. The most abundant species were, in decreasing order, Melanthera nivea, Rhynchelytrum repens, Waltheria indica, Amaranthus scariosus, Digitaria bicornis, and Cenchrus pilosus. Herbs were the prevailing growth form (> 80% of total richness). No clear pattern was observed in the seed bank related to soil type; however, seed bank characteristics tended to be associated with the time of use of the agricultural fi elds, a variable that was not controlled in the study. Seed bank species richness was signifi cantly larger in the dry season, and although seed density showed a similar trend, it was not signifi cant. The studied seed banks contain no elements of the regional primary tropical dry forest, which suggests that seed banks in deforested areas cannot guarantee their maintenance beyond forested areas.
Timely scientific opinions

Intent. The intent of Learned Discourses is to provide a forum for open discussion. These articles reflect the professional opinions of the authors regarding scientific issues. They do not represent SETAC positions or policies. And, although they are subject to editorial review for clarity, consistency, and brevity, these articles are not peer reviewed. The Learned Discourses date from 1996 in the North America SETAC News and, when that publication was replaced by the SETAC Globe, continued there through 2005. The continued success of Learned Discourses depends on our contributors. We encourage timely submissions that will inform and stimulate discussion. We expect that many of the articles will address controversial topics, and promise to give dissenting opinions a chance to be heard. Rules. All submissions must be succinct: no longer than 1000 words, no more than 6 references, and at most one table or figure. Reference format must follow the journal requirement found on the Internet at http://www. setacjournals.org. Topics must fall within IEAM’s sphere of interest. Submissions. All manuscripts should be sent via email as Word attachments to Peter M Chapman (peter@chapmanenviro.com).
Axonal Regulation of Schwann Cell Proliferation and Survival and the Initial Events of Myelination Requires PI 3-Kinase Activity

In this report, we have investigated the signaling pathways that are activated by, and mediate the effects of, the neuregulins and axonal contact in Schwann cells. Phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein kinase kinase (MAPK kinase) are strongly activated in Schwann cells by glial growth factor (GGF), a soluble neuregulin, and by contact with neurite membranes; both kinase activities are also detected in Schwann cell-DRG neuron cocultures. Inhibition of the PI 3-kinase, but not the MAP kinase, pathway reversibly inhibited Schwann cell proliferation induced by GGF and neurites. Cultured Schwann cells undergo apoptosis after serum deprivation and can be rescued by GGF or contact with neurites; these survival effects were also blocked by inhibition of PI 3-kinase. Finally, we have examined the role of these signaling pathways in Schwann cell differentiation in cocultures. At early stages of coculture, inhibition of PI 3-kinase, but not MAPK kinase, blocked Schwann cell elongation and subsequent myelination but did not affect laminin deposition. Later, after Schwann cells established a one-to-one relationship with axons, inhibition of PI 3-kinase did not block myelin formation, but the myelin sheaths that formed were shorter, and the rate of myelin protein accumulation was markedly decreased. PI 3-kinase inhibition had no observable effect on the maintenance of myelin sheaths in mature myelinated cocultures. These results indicate that activation of PI 3-kinase by axonal factors, including the neuregulins, promotes Schwann cell proliferation and survival and implicate PI 3-kinase in the early events of myelination.
CA 125 as a Screening Test for Ovarian Cancer

Background— Screening for ovarian cancer is based on ultrasound, colour Doppler, and tumour markers. There is only limited evidence on their discriminatory performance and no evidence on their effectiveness in reducing mortality. Objective— To investigate the discriminatory performance of CA 125 as a screening test for ovarian cancer. Methods— A registry of 15 093 serum samples drawn in 1968–72 was linked to the cancer registry. During follow up between 1968 and 1980 24 ovarian cancers were identified. One or two matched case—control design nested within the sample bank was applied and the concentrations of CA 125 were assessed. Results— Case—control differences (relative risk 4.0, 95% confidence interval 1.0 to 15.5 at 20kU/l) were found. Detection rate of the CA 125 test was 21–33% and the true negative rate was 75–98% depending on the cut off level and interval between drawing of the blood sample and diagnosis of the cancer. Conclusion— CA 125 is not a valid screening test if used alone. Case—control differences of borderline significance were found in CA 125 before diagnosis of ovarian cancer, but they were not large enough to provide a sufficient detection rate.
Enthusiasm for cancer screening in the United States.

CONTEXT Public health officials, physicians, and disease advocacy groups have worked hard to educate individuals living in the United States about the importance of cancer screening. OBJECTIVE To determine the public's enthusiasm for early cancer detection. DESIGN, SETTING, AND PARTICIPANTS Survey using a national telephone interview of adults selected by random digit dialing, conducted from December 2001 through July 2002. Five hundred individuals participated (women aged > or =40 years and men aged > or =50 years; without a history of cancer). MAIN OUTCOME MEASURES Responses to a survey with 5 modules: a general screening module (eg, value of early detection, total-body computed tomography); and 4 screening test modules: Papanicolaou test; mammography; prostate-specific antigen (PSA) test; and sigmoidoscopy or colonoscopy. RESULTS Most adults (87%) believe routine cancer screening is almost always a good idea and that finding cancer early saves lives (74% said most or all the time). Less than one third believe that there will be a time when they will stop undergoing routine screening. A substantial proportion believe that an 80-year-old who chose not to be tested was irresponsible: ranging from 41% with regard to mammography to 32% for colonoscopy. Thirty-eight percent of respondents had experienced at least 1 false-positive screening test; more than 40% of these individuals characterized that experience as "very scary" or the "scariest time of my life. " Yet, looking back, 98% were glad they had had the initial screening test. Most had a strong desire to know about the presence of cancer regardless of its implications: two thirds said they would want to be tested for cancer even if nothing could be done; and 56% said they would want to be tested for what is sometimes termed pseudodisease (cancers growing so slowly that they would never cause problems during the persons lifetime even if untreated). Seventy-three percent of respondents would prefer to receive a total-body computed tomographic scan instead of receiving 1000 dollars in cash. CONCLUSIONS The public is enthusiastic about cancer screening. This commitment is not dampened by false-positive test results or the possibility that testing could lead to unnecessary treatment. This enthusiasm creates an environment ripe for the premature diffusion of technologies such as total-body computed tomographic scanning, placing the public at risk of overtesting and overtreatment.
A Pilot Study Using Machine Learning and Domain Knowledge to Facilitate Comparative Effectiveness Review Updating

Background. Comparative effectiveness and systematic reviews require frequent and time-consuming updating. Results of earlier screening should be useful in reducing the effort needed to screen relevant articles. Methods. We collected 16,707 PubMed citation classification decisions from 2 comparative effectiveness reviews: interventions to prevent fractures in low bone density (LBD) and off-label uses of atypical antipsychotic drugs (AAP). We used previously written search strategies to guide extraction of a limited number of explanatory variables pertaining to the intervention, outcome, and study design. We empirically derived statistical models (based on a sparse generalized linear model with convex penalties [GLMnet] and a gradient boosting machine [GBM]) that predicted article relevance. We evaluated model sensitivity, positive predictive value (PPV), and screening workload reductions using 11,003 PubMed citations retrieved for the LBD and AAP updates. Results. GLMnet-based models performed slightly better than GBM-based models. When attempting to maximize sensitivity for all relevant articles, GLMnet-based models achieved high sensitivities (0.99 and 1.0 for AAP and LBD, respectively) while reducing projected screening by 55.4% and 63.2%. The GLMnet-based model yielded sensitivities of 0.921 and 0.905 and PPVs of 0.185 and 0.102 when predicting articles relevant to the AAP and LBD efficacy/effectiveness analyses, respectively (using a threshold of P ≥ 0.02). GLMnet performed better when identifying adverse effect relevant articles for the AAP review (sensitivity = 0.981) than for the LBD review (0.685). The system currently requires MEDLINE-indexed articles. Conclusions. We evaluated statistical classifiers that used previous classification decisions and explanatory variables derived from MEDLINE indexing terms to predict inclusion decisions. This pilot system reduced workload associated with screening 2 simulated comparative effectiveness review updates by more than 50% with minimal loss of relevant articles.
Autonomous search and counter-targeting using Levy search models

In this study, we explore the use of nondeterministic search trajectories to accomplish a two-fold mission of mobile robot search for a stationary target while avoiding counter-targeting by the adversary throughout the operation. We analyze the characteristics associated with a Levy distribution of search leg lengths to generate appropriate randomized search trajectories. We discuss the alteration of the probability distribution of the Levy search as a result of the method utilized to best address the presence of the bounded search area and confine the searcher within its boundaries. Through regression analysis of simulation results, we determine expressions for the coverage ratio evolution of the modified Levy search strategy and the distribution on time to target detection TD, from which we are able to calculate the expected time, E[TD], to detect the target uniformly distributed within the search area. We assert assumptions regarding the adversary's detection and tracking abilities to estimate the expected time, E[TC], required for it to counter target the searcher. From these two expected times, we construct a novel probabilistic mission performance metric that measures the likelihood that the searcher will detect the target before it is counter targeted itself.
Cone photoreceptor recovery after experimental detachment and reattachment: an immunocytochemical, morphological, and electrophysiological study.

PURPOSE To compare the morphologic and functional recovery of the retina after detachment and reattachment in an animal with a cone-dominant retina, the ground squirrel. METHODS Ground squirrel (Spermophilus beecheyi) retinas were detached for 1 day and reattached for 7, 35, or 96 days (n = 2, each time point). Flicker ERGs were recorded 1 day after the detachment and at various times after reattachment. Contrast-response functions were measured for isochromatic modulation and for selective modulation of short-wavelength-sensitive (S) and middle-wavelength-sensitive (M) cones. At the end of the experiment, retinas were prepared for light microscopy or immunocytochemical staining with antibodies to rod opsin, S and M cone opsins, cytochrome oxidase, synaptophysin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), interphotoreceptor-binding protein (IRBP), and peanut agglutinin lectin (PNA). Photoreceptor density maps were created from wholemount preparations labeled with biotinylated PNA and anti-S cone opsin. Cell counts of photoreceptor nuclei and cone outer segments (OS) were compared with flicker ERG data. Cell death was examined by the TUNEL method. RESULTS Reattachment stopped photoreceptor cell death and reversed the disruption of interphotoreceptor matrix as well as the redistribution of Müller cell proteins. It also activated some astrocytes based on anti-GFAP staining. S- and M-cone OS showed a gradual recovery in length after reattachment, and this recovery continued to the longest time points examined. ERG contrast gains also recovered after reattachment, but these reached asymptotic levels by approximately a week after reattachment. There were significant correlations between outer nuclear layer (ONL) cell counts and ERG contrast gains. No differences were noted in the indices of recovery of M and S cones. CONCLUSIONS The ERG can be used to follow specifically the changes in the retina that occur after retinal detachment and reattachment.
Using Atoms to Simplify Distributed Programs Checking

The execution of a distributed program generates a large state space which needs to be checked in testing and debugging. This state space can be reduced by using atoms corresponding to code blocks before performing the checking of the required program properties. This paper presents our results in using atoms which are known at program design time for this purpose. We consider the impact of incomplete or incorrect knowledge of atoms on the validity of checking if a run is indeed atomic with respect to the identified atoms and if it satisfies the required program properties.