gebhart/patrepeval huggingface dataset:
In Silico Screening Based on Predictive Algorithms as a Design Tool for Exon Skipping Oligonucleotides in Duchenne Muscular Dystrophy (2015)

The use of antisense 'splice-switching' oligonucleotides to induce exon skipping represents a potential therapeutic approach to various human genetic diseases. It has achieved greatest maturity in exon skipping of the dystrophin transcript in Duchenne muscular dystrophy (DMD), for which several clinical trials are completed or ongoing, and a large body of data exists describing tested oligonucleotides and their efficacy. The rational design of an exon skipping oligonucleotide involves the choice of an antisense sequence, usually between 15 and 32 nucleotides, targeting the exon that is to be skipped. Although parameters describing the target site can be computationally estimated and several have been identified to correlate with efficacy, methods to predict efficacy are limited. Here, an in silico pre-screening approach is proposed, based on predictive statistical modelling. Previous DMD data were compiled together and, for each oligonucleotide, some 60 descriptors were considered. Statistical modelling approaches were applied to derive algorithms that predict exon skipping for a given target site. We confirmed (1) the binding energetics of the oligonucleotide to the RNA, and (2) the distance in bases of the target site from the splice acceptor site, as the two most predictive parameters, and we included these and several other parameters (while discounting many) into an in silico screening process, based on their capacity to predict high or low efficacy in either phosphorodiamidate morpholino oligomers (89% correctly predicted) and/or 2'O Methyl RNA oligonucleotides (76% correctly predicted). Predictions correlated strongly with in vitro testing for sixteen de novo PMO sequences targeting various positions on DMD exons 44 (R² 0.89) and 53 (R² 0.89), one of which represents a potential novel candidate for clinical trials. We provide these algorithms together with a computational tool that facilitates screening to predict exon skipping efficacy at each position of a target exon.
Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04) (2018)

Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.
SIoT: Giving a Social Structure to the Internet of Things (2011)

The actual development of the Internet of Things (IoT) needs major issues related to things' service discovery and composition to be addressed. This paper proposes a possible approach to solve such issues. We introduce a novel paradigm of "social network of intelligent objects", namely the Social Internet of Things (SIoT), based on the notion of social relationships among objects. Following the definition of a possible social structure among objects, a preliminary architecture for the implementation of SIoT is presented. Through the SIoT paradigm, the capability of humans and devices to discover, select, and use objects with their services in the IoT is augmented. Besides, a level of trustworthiness is enabled to steer the interaction among the billions of objects which will crowd the future IoT.
Notch Signaling in Blood Vessels (2007)

It has become increasingly clear that the Notch signaling pathway plays a critical role in the development and homeostasis of the cardiovascular system. This notion has emerged from loss- and gain-of-function analysis and from the realization that several hereditary cardiovascular disorders originate from gene mutations that have a direct impact on Notch signaling. Current research efforts are focused on determining the specific cellular and molecular effects of Notch signaling. The rationale for this has stemmed from the clinical importance and therapeutic potential of modulating vascular formation during various disease states. A more complete appreciation of Notch signaling, as it relates to vascular morphogenesis, requires an in-depth knowledge of expression patterns of the various signaling components and a comprehensive understanding of downstream targets. The goal of this review is to summarize current knowledge regarding Notch signaling during vascular development and within the adult vascular wall. Our focus is on the genetic analysis and cellular experiments that have been performed with Notch ligands, receptors, and downstream targets. We also highlight questions and controversies regarding the contribution of this pathway to vascular development.
Monodisperse drops templated by 3D-structured microparticles (2020)

Abstract The ability to create uniform sub-nanoliter compartments using microfluidic control has enabled new approaches for analysis of single cells and molecules. However, specialized instruments or expertise have been required, slowing the adoption of these cutting-edge applications. Here, we show that 3D-structured microparticles with sculpted surface chemistries template uniformly-sized aqueous drops when simply mixed with two immiscible fluid phases. In contrast to traditional emulsions, particle-templated drops of a controlled volume occupy a minimum in the interfacial energy of the system, such that a stable monodisperse state results with simple and reproducible formation conditions. We describe techniques to manufacture microscale drop-carrier particles and show that emulsions created with these particles prevent molecular exchange, concentrating reactions within the drops, laying a foundation for sensitive compartmentalized assays with minimal instrumentation.
cis Elements and trans-Acting Factors Affecting Regulation of a Nonphotosynthetic Light-Regulated Gene for Chloroplast Glutamine Synthetase (1995)

The glutamine synthetase (GS) gene family in pea (Pisum sativum) consists of four nuclear genes encoding distinct isoenzymes. Molecular studies have show that the GS2 gene encoding chloroplast-localized GS is expected in specific cell types and is regulated by diverse factors such as light and photorespiration. Here, we present the nucleotide sequence of the pea GS2 gene promoter. To identify the elements involved in regulation of GS2 expression, GS2 promoter-deletion analyses were performed using GS2-GUS fusions in tobacco (Nicotiana tabacum). This analysis revealed that the GS2 transit peptide is not required for mesophyll cell-specific expression of beta-glucuronidase (GUS). GUS activity was induced 2- to 4-fold in light-grown versus etiolated T1 seedlings. However, high levels of GUS activity were observed in etiolated seedlings. This observation demonstrated that regulation of expression of GS2, a nonphotosynthetic light-regulated gene, involves additional factors. A 323-bp GS2 promoter sequence is sufficient to confer light regulation to the GUS reporter gene in leaves of mature transgenic tobacco. Light-regulated expression of this pea gene promoter is observed in both tobacco and Arabidopsis, suggesting that the regulatory elements are conserved. Gel-shift analysis detected DNA-protein complexes formed with potential transcription elements within this short, light-responsive GS2 promoter fragment.
A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. (1993)

To directly assess c-myc function in cellular proliferation, differentiation, and embryogenesis, we have used homologous recombination in embryonic stem cells to generate both heterozygous and homozygous c-myc mutant ES cell lines. The mutation is a null allele at the protein level. Mouse chimeras from seven heterozygous cell lines transmitted the mutant allele to their offspring. The analysis of embryos from two clones has shown that the mutation is lethal in homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally smaller and retarded in development compared with their littermates. Pathologic abnormalities include the heart, pericardium, neural tube, and delay or failure in turning of the embryo. Heterozygous females have reduced fertility owing to embryonic resorption before 9.5 days of gestation in 14% of implanted embryos. c-Myc protein is necessary for embryonic survival beyond 10.5 days of gestation; however, it appears to be dispensable for cell division both in ES cell lines and in the embryo before that time.
Cloning, sequencing and oocyte-specific expression of the marmoset sperm receptor protein, ZP3 (1993)

The zona pellucida surrounding the mammalian oocyte contains a major glycoprotein species, ZP3, that serves as a cell- and species-specific receptor for spermatozoa. In this study we have determined the primary amino acid structure of marmoset ZP3 (marZP3) and examined the expression of marZP3 mRNA within the ovary. The marZP3 gene possesses an open reading frame of 1272 nucleotides which is expressed specifically by the oocyte and encodes a polypeptide chain of 424 amino acids that exhibits 91% homology with the human ZP3 sequence. The disparity between these molecules was confined to a short domain spanning residues 322-352; otherwise the molecules were very similar, showing conservation of many structural features including the N-linked glycosylation sites, location and number of cysteine and proline residues and hydrophobicity profile. The results of this study have important implications for the use of the marmoset monkey as an animal model for the development of contraceptive vaccines targeting ZP3.
Cellular Microcystin Content in N-Limited Microcystis aeruginosa Can Be Predicted from Growth Rate (2001)

Cell quotas of microcystin (Q(MCYST); femtomoles of MCYST per cell), protein, and chlorophyll a (Chl a), cell dry weight, and cell volume were measured over a range of growth rates in N-limited chemostat cultures of the toxic cyanobacterium Microcystis aeruginosa MASH 01-A19. There was a positive linear relationship between Q(MCYST) and specific growth rate (mu), from which we propose a generalized model that enables Q(MCYST) at any nutrient-limited growth rate to be predicted based on a single batch culture experiment. The model predicts Q(MCYST) from mu, mu(max) (maximum specific growth rate), Q(MCYSTmax) (maximum cell quota), and Q(MCYSTmin) (minimum cell quota). Under the conditions examined in this study, we predict a Q(MCYSTmax) of 0.129 fmol cell(-1) at mu(max) and a Q(MCYSTmin) of 0.050 fmol cell(-1) at mu = 0. Net MCYST production rate (R(MCYST)) asymptotes to zero at mu = 0 and reaches a maximum of 0.155 fmol cell(-1) day(-1) at mu(max). MCYST/dry weight ratio (milligrams per gram [dry weight]) increased linearly with mu, whereas the MCYST/protein ratio reached a maximum at intermediate mu. In contrast, the MCYST/Chl a ratio remained constant. Cell volume correlated negatively with mu, leading to an increase in intracellular MCYST concentration at high mu. Taken together, our results show that fast-growing cells of N-limited M. aeruginosa are smaller, are of lower mass, and have a higher intracellular MCYST quota and concentration than slow-growing cells. The data also highlight the importance of determining cell MCYST quotas, as potentially confusing interpretations can arise from determining MCYST content as a ratio to other cell components.
한국과 중국의 재외동포네트워크정책 비교연구 -오프라인(off-Line)정책을 중심으로- (2011)

With the rapid development of globalization, the government should make the right judgments and formulate the suitable policies to facilitate its own national development. However, how to judge the developing trend of globalization and how to make the suitable policy? The answer is to set a benchmarking for all the possible polices. By comparing the policies among different countries, the right policy fitting the trend of globalization and benefiting its own country could be made. Through comparing the network policy of overseas compatriot between China and South Korea, this paper exhibits the common and different points between these two countries and proposes some implications for overseas Koreans act. First, encouraging overseas Koreans to invest to Korea, meanwhile, making and conducting the preferential treatment policy to them. Second, the local government should keep a great interest to the overseas Koreans. Third, it is necessary to strengthen the long-term bonds than the economic performance of short-term.
Computer model for glucose‐limited growth of a single cell of Escherichia coli B/r‐A (1984)

A computer model is described which is capable of predicting changes in cell composition, cell size, cell shape, and the timing of chromosome synthesis in response to changes in external glucose limitation. The model is constructed primarily from information on unrestricted growth in glucose minimal medium. The ability of the model to make reasonable quantitative predictions under glucose-limitation is a test of the plausibility of the basic biochemical mechanisms included in the model. Such a model should be of use in differentiating among competing hypotheses for biological mechanisms and in suggesting as yet unobserved phenomena. The last two points are illustrated with the testing of a mechanism for the control of the initiation of DNA synthesis and predictions on cellwidth variations during the division cycle.
Estimating the Number of Species: A Review (1993)

How many kinds are there? Suppose that a population is partitioned into C classes. In many situations interest focuses not on estimation of the relative sizes of the classes, but on estimation of C itself. For example, biologists and ecologists may be interested in estimating the number of species in a population of plants or animals, numismatists may be concemed with estimating the number of dies used to produce an ancient coin issue, and linguists may be interested in estimating the size of an author's vocabulary. In this article we review the problem of statistical estimation of C. Many approaches have been proposed, some purely data-analytic and others based in sampling theory. In the latter case numerous variations have been considered. The population may be finite or infinite. If finite, samples may be taken with replacement (multinomial sampling) or without replacement (hypergeometric sampling), or by Bernoulli sampling; if infinite, sampling may be multinomial or Bernoulli, or the sample may be the result of random Poisson contributions of each dass. Given a sampling model, one may approach estimation of C via a parametric or nonparametric formulation; in either case there may be frequentist and Bayesian procedures. We begin by discussing the existing literature on this problem (over 120 references), organizing it by sampling model, population specification, and philosophy of estimation. We find that (a) the problem is quite resistant to statistical solution, essentially because no matter how many classes have been observed, there may still be a large number of very small unobserved classes; (b) many closely related estimation procedures have been developed independently and have not yet been compared; (c) there is not as yet a globally preferable estimator of C, although for some models there is an acceptable estimator (for some not even this is true); and (d) there are promising directions for research to pursue; for example, it appears possible to exploit estimates of the “coverage” of the sample (the total proportion of the population represented by the observed classes) to improve the accuracy of estimators of the number of classes. Finally, we make specific recommendations for future research, regarding parametric estimation, coverage-based estimation, resampling methods, Poisson process representation of sampling models, and frequentist decision theory.
Interleukin 18 gene polymorphisms predict risk and outcome of Alzheimer's disease (2007)

As IL-18 cytokine promoter gene polymorphisms have been previously described to have functional consequences on IL-18 expression, it is possible that individuals with a prevalent IL-18 gene variant have a dysregulated immune response, suggesting that IL-18 mediated immune mechanisms may play a crucial role in AD.
Structure-Guided Transformation of Channelrhodopsin into a Light-Activated Chloride Channel (2014)

Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.
Theory of Primary Photoexcitations in Donor-Acceptor Copolymers (2015)

We present a generic theory of primary photoexcitations in low band gap donor-acceptor conjugated copolymers. Because of the combined effects of strong electron correlations and broken symmetry, there is considerable mixing between a charge-transfer exciton and an energetically proximate triplet-triplet state with an overall spin singlet. The triplet-triplet state, optically forbidden in homopolymers, is allowed in donor-acceptor copolymers. For an intermediate difference in electron affinities of the donor and the acceptor, the triplet-triplet state can have a stronger oscillator strength than the charge-transfer exciton. We discuss the possibility of intramolecular singlet fission from the triplet-triplet state, and how such fission can be detected experimentally.
The Retreat of Sociologists into the Present (1987)

Not much attention has been paid to the retreat of sociologists into the present. This retreat, their flight from the past, became the dominant trend in the development of sociology after the Second World War and, like this development itself, was essentially unplanned. The immediate present into which sociologists are retreating, however, constitutes just one small momentary phase within the vast stream of humanity’s development, which, coming from the past, debouches into the present and thrusts ahead toward possible futures. The human population has undergone an unplanned process of growth, in more than purely numerical terms and in spite of all fluctuations. In many cases economic and party establishments have moved ahead of them to the top of the power and status hierarchy. Scientific establishments as specialists for the production and transmission of basic knowledge, as the main providers of new means of orientation in their societies, have taken over functions formerly performed by priests.
Comparisons of the Glycosylation of a Monoclonal Antibody Produced under Nominally Identical Cell Culture Conditions in Two Different Bioreactors (2000)

The murine B-lymphocyte hybridoma cell line, CC9C10, was grown in serum-free continuous culture at steady-state dissolved oxygen (DO) concentrations of 10%, 50%, and 100% of air saturation in both LH Series 210 (LH) and New Brunswick Scientific (NBS) CelliGen bioreactors. All culture parameters were monitored and controlled and were nominally identical at steady state in the two bioreactors. The secreted monoclonal antibody (mAb), an immunoglobulin G(1), was purified and subjected to enzymatic deglycosylation using peptide N-glycosidase F (PNGase F). Asparagine-linked (N-linked) oligosaccharide pools released from mAb samples cultured in each bioreactor at each of the three DO setpoints were analyzed by high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). The predominant N-linked structures were core-fucosylated asialo biantennary chains with varying galactosylation. There were also minor amounts of monosialyl oligosaccharides and trace amounts of afucosyl oligosaccharides. The level of DO affects the glycosylation of this mAb. A definite reduction in the level of galactosylation of N-glycan chains was observed at lower DO in both bioreactors, as evidenced by prominent increases in the relative amounts of agalactosyl chains and decreases in the relative amounts of digalactosyl chains-with the relative amounts of monogalactosyl chains being comparatively constant. However, the quantitative results are not precise matches between the two bioreactors. The effect of DO on galactosylation is less pronounced in the NBS bioreactor than in the LH bioreactor, particularly the shift between the relative amounts of agalactosyl and digalactosyl chains in 10% and 50% DO. There are also perceptibly higher levels of sialylation of the mAb glycans in the NBS bioreactor than in the LH bioreactor at all three DO setpoints. The results indicate that the DO effect is not bioreactor specific and that nominally identical steady-state conditions in different chemostat bioreactors may still lead to some incongruities in glycosylation, possibly due to the particular architectures of the bioreactors and the design of their respective monitoring and control systems. The observed differences in N-linked glycosylation of the mAb secreted by the hybridoma grown in the LH and NBS bioreactors may be explained by the differences in oxygen supply and control strategies between the two bioreactors.
Derivation and Potential Applications of Human Embryonic Stem Cells (2002)

Embryonic stem cells are pluripotent cell lines that are derived from the blastocyst-stage early mammalian embryo. These unique cells are characterized by their capacity for prolonged undifferentiated proliferation in culture while maintaining the potential to differentiate into derivatives of all three germ layers. During in vitro differentiation, embryonic stem cells can develop into specialized somatic cells, including cardiomyocytes, and have been shown to recapitulate many processes of early embryonic development. The present review describes the derivation and unique properties of the recently described human embryonic stem cells as well as the properties of cardiomyocytes derived using this unique differentiating system. The possible applications of this system in several cardiac research areas, including developmental biology, functional genomics, pharmacological testing, cell therapy, and tissue engineering, are discussed. Because of their combined ability to proliferate indefinitely and to differentiate to mature tissue types, human embryonic stem cells can potentially provide an unlimited supply of cardiomyocytes for cell therapy procedures aiming to regenerate functional myocardium. However, many obstacles must still be overcome on the way to successful clinical utilization of these cells.