question:You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.Question: What is the link between ultraconserved elements and three-dimensional mammalian genome organization?Context: Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization.We find that UCEs are enriched within contact domains and, further, that the subset of UCEs within domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither overrepresented nor underrepresented, but those present in loop anchors are enriched for splice sites. Finally, as the relationships between UCEs and human Hi-C features are conserved in mouse, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.

question:You are presented with multiple paper abstracts, alongside the associated literature review and chapter titles. Given the provided information, you are going to do a literature review. Please generate a coherent literature review that synthesizes the content, draws connections between different works, highlights major findings, and identifies any gaps in the existing research.Literature Review Title: A Review of Interference Reduction in Wireless Networks Using Graph Coloring Methods Chapter Title: RELATED WORK 1. Abstract of Cited Paper (BIB001): We present the first location-oblivious distributed unit disk graph coloring algorithm having a provable performance ratio of three (i.e. the number of colors used by the algorithm is at most three times the chromatic number of the graph). This is an improvement over the standard sequential coloring algorithm that has a worst case lower bound on its performance ratio of 4−3/k (for any k>2, where k is the chromatic number of the unit disk graph achieving the lower bound) (Tsai et al., in Inf. Process. Lett. 84(4):195–199, 2002). We present a slightly better worst case lower bound on the performance ratio of the sequential coloring algorithm for unit disk graphs with chromatic number 4. Using simulation, we compare our algorithm with other existing unit disk graph coloring algorithms.Literature Review:

question:You are presented with multiple paper abstracts, alongside the associated literature review and chapter titles. Given the provided information, you are going to do a literature review. Please generate a coherent literature review that synthesizes the content, draws connections between different works, highlights major findings, and identifies any gaps in the existing research.Literature Review Title: Survey of Spectrum Sharing for Inter-Technology Coexistence Chapter Title: B. Spectrum Sharing at Layer 2 1. Abstract of Cited Paper (BIB001): As the spectral efficiency of a point-to-point link in cellular networks approaches its theoretical limits, with the forecasted explosion of data traffic, there is a need for an increase in the node density to further improve network capacity. However, in already dense deployments in today's networks, cell splitting gains can be severely limited by high inter-cell interference. Moreover, high capital expenditure cost associated with high power macro nodes further limits viability of such an approach. This article discusses the need for an alternative strategy, where low power nodes are overlaid within a macro network, creating what is referred to as a heterogeneous network. We survey current state of the art in heterogeneous deployments and focus on 3GPP LTE air interface to describe future trends. A high-level overview of the 3GPP LTE air interface, network nodes, and spectrum allocation options is provided, along with the enabling mechanisms for heterogeneous deployments. Interference management techniques that are critical for LTE heterogeneous deployments are discussed in greater detail. Cell range expansion, enabled through cell biasing and adaptive resource partitioning, is seen as an effective method to balance the load among the nodes in the network and improve overall trunking efficiency. An interference cancellation receiver plays a crucial role in ensuring acquisition of weak cells and reliability of control and data reception in the presence of legacy signals. 2. Abstract of Cited Paper (BIB002): Orthogonal Frequency Division Multiplexing Access (OFDMA) has been increasingly deployed in various emerging and evolving cellular systems to reduce interference and improve overall system performance. However, in these systems Inter-Cell Interference (ICI) still poses a real challenge that limits the system performance, especially for users located at the cell edge. Inter-cell interference coordination (ICIC) has been investigated as an approach to alleviate the impact of interference and improve performance in OFDMA-based systems. A common ICIC technique is interference avoidance in which the allocation of the various system resources (e.g., time, frequency, and power) to users is controlled to ensure that the ICI remains within acceptable limits. This paper surveys the various ICIC avoidance schemes in the downlink of OFDMA-based cellular networks. In particular, the paper introduces new parameterized classifications and makes use of these classifications to categorize and review various static (frequency reuse-based) and dynamic (cell coordination-based) ICIC schemes. 3. Abstract of Cited Paper (BIB003): Motivated by stringent power constraints, duty cycling - the practice of turning a mote's radio on and off to conserve energy - has become a fundamental mechanism in the design of Wireless Sensor Networks. Because of its importance, a variety of approaches to duty cycling have emerged during the last decade and are being now proposed with increasingly ambitious goals, such as achieving ultra low duty cycles as low as 0.1%. Such propositions differ mostly in their reliance on nodes' synchronization, which, in turn, translates into different hardware requirements and implementation complexity. However, duty cycling may also differ in other aspects as topology dependency, network density requirements and increase in end-to-end delay. This paper organizes the most important proposals into a taxonomy and provides insights into their strengths and weaknesses in relation to important characteristics of applications, mote's hardware and network deployments. 4. Abstract of Cited Paper (BIB004): Channel bonding (CB) is a proven technique to increase bandwidth and reduce delays in wireless networks. It has been applied in traditional wireless networks such as cellular networks and wireless local area networks along with the emerging cognitive radio networks. This paper first focuses on providing a survey of CB schemes for traditional wireless networks such as cellular networks, wireless local area networks, and wireless sensor networks, and then provides a detailed discussion on the CB schemes proposed for cognitive radio networks. Finally, we highlight a number of issues and challenges regarding CB in cognitive radio sensor networks and also provide some guidelines on using CB schemes in these futuristic networks.Literature Review:

question:You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.Paper text: gpgeneral practitionerhoncodehealth on the internet codeipdinvasive pneumococcal diseaseitinformation technologynvppnational vaccine prevention plan health on the internet code invasive pneumococcal disease information technology national vaccine prevention planthe development of the app is a part of the project on increasing the population 's awareness of invasive pneumococcal disease and has been supported by sponsorship from pfizer s.r.l .

question:You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: ["Outcome", "Participant", "Intervention"].Please return the output as a JSON object of the format: {"Participant" : ["patients with COPD", ...], "Intervention" : ["Atenolol", ...], "Outcome" : ["blood pressure", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].Only output the JSON object and do not include any additional text.Abstract:Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia : an intergroup molecular study . In each case of acute promyelocytic leukemia ( APL ) one of three PML-RAR alpha mRNA types is produced , depending on the break/fusion site in the PML gene that is linked to a common RAR alpha gene segment : a short ( S ) -form type , PML exon 3 RAR alpha exon 3 ; a long ( L ) -form type , PML exon 6 RAR alpha exon 3 ; or a variable ( V ) -form type , variably deleted PML exon 6 RAR alpha exon 3 . We evaluated whether PML-RAR alpha mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group , the Southwest Oncology Group , and the Cancer and Leukemia Group B . Of 279 clinically eligible cases , 230 were molecularly evaluable , and of these , 111 were randomized to receive remission induction therapy with all-trans retinoic acid ( ATRA ) and 119 with conventional chemotherapy . Nine cases not excluded by central pathology review were PML-RAR alpha negative , and notably , none of five of these cases treated with ATRA achieved complete remission ( CR ) . Among 221 PML-RAR alpha-positive cases , there were 82 S-form cases ( 37 % ) , 121 L-form cases ( 55 % ) , and 18 V-form cases ( 8 % ) . Before any antileukemic therapy , the S-form type , compared with the L-form type , was associated with higher values for the white blood cell ( WBC ) count ( median 2,500/microL v 1,600/microL ; P = .009 ) , the percentage of blood blasts plus promyelocytes ( median 29 % v 8.5 % ; P = .03 ) , and the absolute blood blasts plus promyelocytes ( 884/microL v 126/microL ; P = .019 ) . Also , an increased percentage of S-form versus L-form cases had the M3 variant phenotype , 24 % v 12 % ( P = .036 ) . There were no differences between S-form and L-form cases in either CR rate ( 79 % v 69 % ; P = .14 ) or disease free survival distribution ( multivariate analysis adjusting for the association of S-form type and higher WBC count ; P = .40 ) . We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RAR alpha mRNA , per se , does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients .

question:You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.Title: Genetic Diversity in the Interference Selection Limit}Article:Abstract:Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasingly severe as the density of selected polymorphisms increases. Here, we describe a simple limit that emerges when interference is common, in which the fitness effects of individual mutations play a relatively minor role. Instead, similar to models of quantitative genetics, molecular evolution is determined by the variance in fitness within the population, defined over an effectively asexual segment of the genome( a “linkage block”). We exploit this insensitivity in a new “coarse-grained” coalescent framework, which approximates the effects of many weakly selected mutations with a smaller number of strongly selected mutations that create the same variance in fitness. This approximation generates accurate and efficient predictions for silent site variability when interference is common. However, these results suggest that there is reduced power to resolve individual selection pressures when interference is sufficiently widespread, since a broad range of parameters possess nearly identical patterns of silent site variability.Introduction:Natural selection maintains existing function and drives adaptation, altering patterns of diversity at the genetic level. Evidence from microbial evolution experiments[1],[2] and natural populations of nematodes[3], fruit flies[4],[5], and humans[6],[7] suggests that selection is common and that it can impact diversity on genome-wide scales. Understanding these patterns is crucial, not only for studying selection itself, but also for inference of confounded factors such as demography or population structure. However, existing theory struggles to predict genetic diversity when many sites experience selection at the same time, which limits our ability to interpret variation in DNA sequence data. Selection on individual nucleotides can be modeled very precisely, provided that the sites evolve in isolation. But as soon as they are linked together on a chromosome, selection creates correlations between nucleotides that are difficult to disentangle from each other. This gives rise to a complicated many-body problem, where even putatively neutral sites feel the effects of selection on nearby regions. Many authors neglect these correlations, or assume that they are equivalent to a reduction in the effective population size, so that individual sites evolve independently. This assumption underlies several popular methods for inferring selective pressures and demographic history directly from genetic diversity data[8]–[12]. Yet there is also extensive literature( recently reviewed in Ref.[13]) which shows how the independent sites assumption breaks down when the chromosome is densely populated with selected sites. When this occurs, the fitness effects and demographic changes inferred by these earlier methods become increasingly inaccurate[14],[15]. Linkage plays a more prominent role in models of background selection[16] and genetic hitchhiking[17], which explicitly model how strong negative and strong positive selection distort patterns of diversity at linked sites. Although initially formulated for a two-site chromosome, both can be extended to larger genomes as long as the selected sites are sufficiently rare that they can still be treated independently. Simple analytical formulae can be derived in this limit, motivating extensive efforts to distinguish signatures of background selection and hitchhiking from sequence variability in natural populations( see Ref.[18] for a recent review). However, this data has uncovered many instances where selection is neither as rare nor as strong as these simple models require[7],[19]–[24]. Instead, substantial numbers of selected polymorphisms segregate in the population at the same time, and these mutations interfere with each other as they travel towards fixation or loss. The genetic diversity in this weak Hill-Robertson interference[25] or interference selection[26] regime is poorly understood, especially in comparison to background selection or genetic hitchhiking. The qualitative behavior has been extensively studied in simulation[22],[25]–[29], and this has led to a complex picture in which both genetic drift and chance associations between linked mutations( genetic draft) combine to generate large fluctuations in the frequencies of selected alleles, and the occasional fixation of deleterious mutations due to Muller's ratchet. In principle, these forward simulations can also be used for inference or model comparison using approximate likelihood methods[7],[30], but in practice, performance concerns severely limit both the size of the parameter space and the properties of the data that can be analyzed in this way. Here, we will show that in spite of the complexity observed in earlier studies, simple behaviors do emerge when interference is sufficiently common. When fitness differences are composed of many individual mutations, we obtain a type of central limit theorem, in which diversity at putatively neutral sites is determined primarily by the variance in fitness within the population over a local, effectively asexual segment of the genome. This limit is analogous to the situation in quantitative genetics, where the evolution of any trait depends only on the genetic variance for the trait, rather than the details of the dynamics of individual loci. We exploit this simplification to establish a coalescent framework for generating predictions under interference selection, which is based on a coarse-grained, effective selection strength and effective mutation rate. This leads to accurate and efficient predictions for a regime that is often implicated in empirical data, but has so far been difficult to model more rigorously. Our method also has important qualitative implications for the interpretation of sequence data in the interference selection regime, which we address in the Discussion.Discussion:Interfering mutations display complex dynamics that have been difficult to model with traditional methods. Here, we have shown that simple behavior emerges in the limit of widespread interference. When fitness variation is composed of many individual mutations, the magnitudes and signs of their fitness effects are relatively unimportant. Instead, molecular evolution is controlled by the variance in fitness within the population over some effectively asexual segment of the genome. This implies a corresponding symmetry, in which many weakly selected mutations combine to mimic the effects of a few strongly deleterious mutations with the same variance in fitness. We have exploited this symmetry in our “coarse-grained” coalescent framework, which generates efficient predictions across a much broader range of selection pressures than was previously possible. Our results are consistent with previous studies that have investigated interference selection in silico[22],[25]–[29],[44], but our coarse-grained model offers a different perspective on the relevant processes that contribute to molecular evolution in this regime. By using the term interference selection, we have tried to emphasize that interference( i. e., correlations in the frequencies of selected alleles) is the distinguishing feature that separates these populations from the traditional background selection regime. Previous work, on the other hand, has argued that virtually all of the deviations from the background selection limit can be attributed to fluctuations in the fitness distribution and the effects of Muller's ratchet[22],[41],[43]. Yet our coarse-grained framework includes neither of these complications directly, and the quantitative behavior is unchanged even when beneficial compensatory mutations balance the loss of fitness due to Muller's ratchet. Moreover, fitness class fluctuations and the ratchet are arguably maximized in neutral populations[52], which are well-characterized by the neutral coalescent. Instead, our results show that we can capture many aspects of silent site diversity simply by correcting for the average bias in the fitness distribution away from the prediction in Eq.( 1), similar to the findings of Ref.[47]. In order to predict this bias from first principles, it is crucial to account for correlations in the frequencies of selected mutations, similar to rapidly adapting populations[44],[65]. Of course, the degree of interference in any particular organism is ultimately an empirical question— one that hinges on the relative strengths of mutation, selection, and recombination. Although interference is often observed in microbes and viruses[76]–[79], its prevelance in higher sexual organisms is still controversial because it is difficult to estimate these parameters in the wild. Mutation and recombination rates can be measured directly( at least in principle), but population sizes and selection strengths can only be inferred from a population genetic model, and these have historically struggled to include the effects of selection on linked sites. Many estimates of “” ignore linkage by fiat( e. g.[80]) under the assumption that sites evolve independently. But these estimates become unreliable precisely when small- and intermediate-effect mutations are most common, and the reasons for this are apparent from Figure 4. All of the distortions in Figure 4 C and Figure 4 D would be mistakenly ascribed to demography( or in the case of Figure 4 E, population substructure), thereby biasing the estimates of selection at nonsynonymous sites. At best, these estimates of “” represent measurements of, which carry little information about the true strength of selection( Ns) or even the potential severity of interference. For example, all of the populations in Figure 8 have Ns = 10 and, even though they fall in the interference selection regime, and show a strong distortion in minor allele frequency that cannot be explained by Eq.( 2). In other words, we cannot conclude that interference is negligible just because “”, as inferred from data, is larger than one. More sophisticated analyses avoid these issues with simulations of the underlying genomic model[7],[22],[29],[30]. In principle, this approach can provide robust estimates of the underlying parameter combinations that best describe the data. But in practice, simulation-based methods suffer from two major shortcomings which are highlighted by the symmetry above. We have seen that strongly-interfering populations with the same variance in fitness possess nearly identical patterns of genetic diversity. This suggests a degree of “sloppiness”[81] in the underlying model, which can lead to large intrinsic uncertainties in the parameter estimates and a strong sensitivity to measurement noise. A more fundamental problem is identifying the nearly equivalent populations in the first place. Even in our simplified model, large genomes are computationally expensive to simulate, and this obviously limits both the number of dependent variables and the various parameter combinations that can be explored in a single study. We have shown that sets of equivalent populations lie along a single line( namely, the line of constant Nσ) in the larger parameter space, which can easily be missed in a small survey unless the parameters are chosen with this degeneracy in mind. In this way, our theoretical predictions can aid existing simulation methods by identifying equivalent sets of parameters that also describe the data. As an example, we consider the D. melanogaster dot chromosome that inspired the parameter combination in Figure 4 A. Earlier, we showed that the reduction in silent site diversity on this chromosome() is consistent with the parameters Ns≈30, NU≈300, and NR≈0, which fall in the middle of the interference selection regime( Ref.[29], see Methods). Our calculations allow us to predict other parameter combinations with the same patterns of diversity, and we plot the simulated frequency spectrum for three of these alternatives in Figure 6. We see that even with highly resolved frequency spectra( unavailable in the original dataset), there is little power to distinguish between these predicted alternatives despite rather large differences in the underlying parameters. However, this “resolution limit” suggests that individual fitness effects are not the most interesting quantity to measure when interference is common. Individual fitness effects may play a central role in single-site models, but we have shown that global properties like the variance in fitness and the corresponding linkage scale are more relevant for predicting evolution in interfering populations. Estimating these quantities directly may therefore be preferable in practice. Our coarse-grained predictions provide a promising new framework for inferring these quantities based on allele frequency data or genealogical reconstruction. A concrete implementation presents a number of additional challenges, mostly to ensure a proper exploration of the high-dimensional parameter space, but this remains an important avenue for future work. Finally, our findings suggest a qualitative shift in the interpretations gleaned from previous empirical studies. We have provided further evidence that even weak purifying selection, when aggregated over a sufficiently large number of sites, can generate strong deviations from neutrality. Moreover, these signals can resemble more “biologically interesting” scenarios like recurrent sweeps, large-scale demographic change, or selection on the silent sites themselves. Here we refer not only to the well-known reduction in diversity and skew towards rare alleles, but also to the topological imbalance in the genealogy( or the “U-shaped” frequency spectrum), and the strong correlations in these quantities with the rate of recombination. Since weakly deleterious mutations are already expected to be common[60], they may constitute a more parsimonious explanation for observed patterns of diversity unless they can be rejected by a careful, quantitative comparison of the type advocated above. At the very least, these signals should not be interpreted as prima facie evidence for anything more complicated than weak but widespread purifying selection.