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Finding top-k frequent items has been a hot issue in databases. Finding top-k persistent items is a new issue, and has attracted increasing attention in recent years. In practice, users often want to know which items are significant, i.e., not only frequent but also persistent. No prior art can address both of the above two issues at the same time. Also, for high-speed data streams, prior art cannot achieve high accuracy when the memory is tight. In this paper, we define a new issue, named finding significant items, and propose a novel algorithm namely LTC to address this issue. It includes two key techniques, Long-tail Restoring and CLOCK, as well as three optimizations. In addition, LTC is extended to support finding significant items with thresholds. We theoretically derive the correct rate and error bound, and conduct extensive experiments on three real datasets to test the performance of LTC. Our experimental results show that LTC can achieve ${10^{5}}$ times higher accuracy in terms of average relative error than other related algorithms. Lastly, LTC is applied to a DDoS detection task and it shows that finding significant items is more powerful than finding frequent items.

We present a process of producing antibacterial AuNPs on a large scale, and the AuNP-based medical dressing prepared using continuous dyeing and finishing machines is promising to be used in clinical antibacterial applications.

Cells cope with and adapt to ever-changing environmental conditions. Sophisticated regulatory networks allow cells to adjust to these fluctuating environments. One such archetypal system is the

Photoionization mass spectrometry (PI-MS) has become a versatile tool in the real-time analysis of volatile organic compounds (VOCs) from the atmosphere or exhaled breath. However, some key species

Deep reinforcement learning (DRL) has been widely used in autonomous control due to its superior performance. DRL-based autonomous control model (ACM) aims to train an agent to achieve self-control and learn optimal policy through pre-defined rewards. Despite the super-human performance, ACM is regarded as a black box, and the interpretation of its internal working mechanism remains a challenge to domain experts. In addition, adjusting the reward settings of ACM is also challenging due to the uncertain relationship between rewards setting and strategies. In this paper, we propose ACMViz, a visual analytics system to explore control strategies at different stages and reveal the relationship between rewards and action patterns. Focusing on controlling a lunar lander, ACMViz investigates different landing trajectories and action sequences to interpret the model and control the training. From our visual analytics of the action patterns, we diagnose and improve reward settings for different control targets. Through our case studies with deep learning experts, we validate the effectiveness of ACMViz.

Satellites detect the distribution of meteorological data worldwide. However, due to the orbital constraints, the satellite can only reach the same area again after one orbiting cycle. The interval between two detections in the same area is long, and the variation of meteorological data between the two detections is unknown. Moreover, meteorological satellite data are only located near the orbit in one cycle, while the global distribution of meteorological data is unknown. Our method allows to train a regression model with only few meteorological satellite data by taking advantage of the recent advances in deep learning. In detail, we train a model-agnostic meta-learning (MAML) model with data from ground stations instead of meteorological satellites and get the initial network parameters. Based on the initial network parameters trained by MAML, we train the regression models again for different areas. We sample the regression curves of all areas by time and get a time series of global meteorological data distribution. Through case studies conducted together with domain experts, we validate the effectiveness of our method.

The demand for leaf area index (LAI) retrieval from spaceborne full-waveform LiDAR increases due to its direct sampling of the three-dimensional forest structure at a near-global scale. However, the nonrandomness (i.e., clumping effect) of canopy composition limits the reliability of LAI derived from two common methods. They either assume a homogeneous scene in the footprint or just correct for the large gaps-induced between-crown clumping. The clumping in the crown is still an unaddressed issue. We proposed a method to compensate occlusion (i.e., lower canopy layers are occluded by the upper canopy in the process of LiDAR measurement), through which the vertical canopy profile can be resolved from the waveform. Further, we developed a method of deriving relative path length distribution that can reflect the heterogeneity of the canopy from the occlusion-corrected waveform. In addition to correcting the between-crown clumping, we corrected the within-crown clumping further using the derived relative path length distribution, based on path length distribution (PATH) theory. We used simulated waveform data with known LAI and GLAS data with corresponding field-measured LAI to test the performance of our and the other two common LAI retrieval methods. Results show that the errors of our approach are the lowest (with an error generally below 10% and the maximum error below 20%, compared with up to 69% and 47% for the other two methods), and it is relatively stable in various scenes. This study demonstrated the potential of improving LAI retrieval through full utilization of full-waveform data.

Cells cope with and adapt to ever-changing environmental conditions. Sophisticated regulatory networks allow cells to adjust to these fluctuating environments. One such archetypal system is the Saccharomyces cerevisiae Pho regulon. When external inorganic phosphate ( P i ) concentration is low, the Pho regulon activates, expressing genes that scavenge external and internal P i . However, the precise mechanism controlling this regulon remains elusive. We conducted a systems analysis of the Pho regulon on the single-cell level under well-controlled environmental conditions. This analysis identified a robust, perfectly adapted Pho regulon state in intermediate P i conditions, and we identified an intermediate nuclear localization state of the transcriptional master regulator Pho4p. The existence of an intermediate nuclear Pho4p state unifies and resolves outstanding incongruities associated with the Pho regulon, explains the observed programmatic states of the Pho regulon, and improves our general understanding of how nature evolves and controls sophisticated gene regulatory networks. We further propose that robustness and perfect adaptation are not achieved through complex network-centric control but by simple transport biophysics. The ubiquity of multitransporter systems suggests that similar mechanisms could govern the function of other regulatory networks as well.

Summary Advances in bioelectronics have great potential to address unsolved biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ϵ-caprolactone), which encapsulates liquid metal to make flexible and biodegradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood-vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelialization process through electrical stimulation and can enable controlled gene delivery into specific parts of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency 3 months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of the vascular tissue-machine interface.

Intimal hyperplasia (IH) in vein grafts (VGs) is a major issue in coronary artery bypass grafting (CABG) surgery. Although external stents can attenuate IH of VGs to some extent, none of the existing external stents have shown satisfactory clinical outcomes. Here we develop a flexible, biodegradable, and conductive external metal-polymer conductor stent (MPCS) that can electroporate the vessel wall and produce a protein that prevents IH. We designed the plasmid DNA encoding the tissue inhibitor of metalloproteinases-3 (TIMP-3) and lyophilized it on the inner surface of the MPCS to deliver into the adventitia and the middle layer of VGs for gene therapy. Coupled with its continuous mechanical support to prevent dilation after implanting, the MPCS can inhibit the IH of VGs significantly in the rabbit model. This proof-of-concept demonstration may aid the development of other implantable bioelectronics for electroporation gene therapy.

Transcription factor binding to a single binding site and its functional consequence in a promoter context are beginning to be relatively well understood. However, binding to clusters of sites has yet to be characterized in depth, and the functional relevance of binding site clusters remains uncertain. We employed a high-throughput biochemical method to characterize transcription factor binding to clusters varying across a range of affinities and configurations. We found that transcription factors can bind concurrently to overlapping sites, challenging the notion of binding exclusivity. Furthermore, compared to an individual high-affinity binding site, small clusters with binding sites an order of magnitude lower in affinity give rise to higher mean occupancies at physiologically-relevant transcription factor concentrations in vitro. To assess whether the observed in vitro occupancies translate to transcriptional activation in vivo, we tested low-affinity binding site clusters by inserting them into a synthetic minimal CYC1 and the native PHO5 S. cerevisiae promoter. In the minCYC1 promoter, clusters of low-affinity binding sites can generate transcriptional output comparable to a promoter containing three consensus binding sites. In the PHO5 promoter, replacing the native Pho4 binding sites with clusters of low-affinity binding sites recovered activation of these promoters as well. This systematic characterization demonstrates that clusters of low-affinity binding sites achieve substantial occupancies, and that this occupancy can drive expression in eukaryotic promoters.

The billion tons of synthetic polymer-based materials (i.e. plastics) produced every year are one of the greatest challenges that humanity has to face. Nature produces even more natural polymers, yet they are sustainable. For example, proteins are sequence-defined natural polymers, that are constantly recycled when living systems feed. Indeed, digestion is the protein depolymerization into amino acids (i.e. the monomers) followed by their re-assembly into new proteins of arbitrarily different sequence and function. This process breaks a common recycling paradigm where a material is recycled into itself. Organisms feed of random protein mixtures that are ‘recycled’ into new proteins whose identity depends on the cell’s needs at the time of protein synthesis. Currently, advanced materials are increasingly made of proteins, but the abovementioned ideal recyclability of such materials has yet to be recognized and established. In this study mixtures of several (up to >30) peptides and/or proteins were depolymerized into their amino acid constituents, and these amino acids were used to synthesize new fluorescent, and bio-active proteins extra-cellularly by using an amino acid-free cell-free transcription-translation system. Proteins with high relevance in materials engineering (β-lactoglobulin films, used for water filtration, or silk fibroin solutions) were successfully recycled into biotechnologically relevant proteins (green, and red fluorescent proteins, catechol 2,3-dioxygenase). The potential long-term impact of this approach to recycling lies in its compatibility with circular-economy models where raw materials remain in use as long as possible, thus reducing the burden on the planet.

Leaf inclination angle distribution plays an important role in indirect leaf area measurement methods. Path length distribution method (PATH) is an indirect leaf area measurement method based on Beer's Law, which has been applied to isolated trees with Terrestrial Laser Scanning (TLS). However, it can only set the leaf projection G to a constant value. In this paper, the PATH method considering leaf inclination models is introduced, which allows the G function to be a variable corresponding to leaf inclination. On the basis of this method, this paper explores the effect of different leaf inclination angle distribution assumptions on the inversion of the leaf area of isolated trees based on TLS. The results show that compared with the measured leaf inclination, the relative errors of the inversion results based on the six typical leaf inclination assumptions are between −14.3 % to +41.2%, which indicates that leaf inclination has a significant effect on the inversion of the leaf area. Further, experiments in this paper show that the mean value of the G function is a relatively accurate representation of it.

Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(e-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.

The FY-3C satellite returns more than 250,000 occultation data each year, each of which records high vertical resolution profiles of various climatic parameters in the range of 0–1000 km above the Earth. These long-term, stable, and globally distributed observations can be used to improve climate modeling and analyze trends in spatial climate. However, traditional methods based on small samples meet challenges in analyzing the multi-dimensional occultation data in large volume. In this paper, we developed OccVis-a visual analytics system for multi-dimensional and multi-scale comparative analysis of occultation data. With a novel workflow, a series of data processing methods are proposed to support data correcting, patching, and clustering. Moreover, a matrix view with two modes is presented for overview, and a detail view along with time series view is provided for further analysis. Domain scientists can easily utilize our system to visually and interactively explore multivariable occultation data at different time and space scales. Finally, we conduct case studies in climate modeling of ionosphere and obtain several preliminary results to demonstrate the usage and effectiveness of our system.

Blattisocius Keegan is a genus of predatory mites in the family Blattisociidae, with potential utility as biological control agents. In the present study, Illumina HiSeq was used to sequence the co...

Indoor positioning systems have been playing an important role in positioning technology research. This kind of technology can be used in many fields in our daily life. For example, people can use it to help firefighters find people in the fire scene, help managers to monitor robots' track in a factory, and so on. And there are many technologies that could be used to locate people or items indoors, such as Bluetooth, ZigBee, and Ultra-wideband (UWB). UWB technology has characteristics of high precision and low power consumption. In this project, we compare the performance of other technologies with UWB in an indoor positioning system, especially their precision in indoor positioning. Some channel characteristics such as Time of Arrival (TOA), direction of arrival (DOA), received signal strength (RSS) will be measured to analyze the position and motion of people or items indoors. In this paper, we improve the performance of a swarm intelligence algorithm in order to make it have higher efficiency and more accuracy to locate indoor items with static states. And then, for dynamic items, we use the Kalman filter algorithm and try to improve its performance to make the track we get in the positioning system closer to the actual track. Through simulation of position and track of items, we could prove the high precision of this indoor positioning system.

Heavy metals (HMs) in farmland soils lead to adverse influences on ecosystem and human health. Despite that, data on quantitative risk from different sources are still scarce. In this study, 100 farmland soil samples in Jiuyuan District were collected and analyzed for selected HMs (As, Cd, Co, Cr, Cu, Mn, Ni, Pb, V and Zn) content characteristics and pollution statuses. The positive matrix factorization (PMF) model combined with the Nemerow integrated risk index (NIRI) and human health risk assessment (HHRA) was used to quantitatively identify the primary risk sources. The results indicated that the mean contents or median values (mg/kg) of 10 HMs were all higher than the background values. The contamination factor (CF) and pollution load index (PLI) revealed that the soil was severely polluted. Based on PMF, the main source of HM pollution was anthropogenic activities, accounting for 78.91%. Sewage irrigation represented the biggest input but was not associated with the highest risk. The results of PMF-based NIRI and PMF-based HHRA showed that the chemical fertilizers and pesticides were the largest and priority risk sources with contribution rates of 38.10% to ecological risk and 34.61 and 32.82% to non-carcinogenic and carcinogenic risk, respectively. In addition, non-carcinogenic risk of children was higher than that of adults, while the carcinogenic risk was the opposite. The integrated approaches were beneficial for priority risk quantification from different sources and can provide direct risk information and effective policy recommendations for management and control of key risk sources.

Narrowing the mechanical mismatch between biological tissues (typically soft) and neural interfaces (hard) is essential for maintaining signal quality for the electrical recording of neural activity. However, only a few materials can satisfy all requirements for such electronics, which need to be both biocompatible and sufficiently soft. Here, a highly stretchable electrode array (SEA) is introduced, based on the liquid metal-polymer conductor (MPC), achieving high mechanical flexibility and good cytocompatability for neural interfaces. By utilizing the MPC, the SEA exhibits high stretchability (≈100%) and excellent cycling stability (>400 cycles). The cytocompatability of the SEA can allow for long-term culturing of primary neurons and enable signal recording of primary hippocampal neurons. In the future, the SEA could serve as a reliable and robust platform for diagnostics in neuronal tissues and greatly advance brain-machine interfaces.

Existing temporary epicardial pacing wires (TPWs) are rigid and non-absorbable, such that they can cause severe complications after cardiac surgery. Here, a soft and absorbable temporary epicardial pacing wire (saTPW) for effectively correcting abnormal heart rates in a rabbit model, such as bradycardia and ventricular premature beat, is developed. The saTPW exhibits excellent conductivity, flexibility, cycling stability (>100 000 cycles), and less inflammatory response during two-month subcutaneous implantation in a rat model. The saTPW which consists of poly(l-lactide-co-e-caprolactone) and liquid metal, can degrade about 13% (mass loss) in the rats over a two-month subcutaneous implantation. It can be absorbed over time in the body. The cytocompatibility and absorbability avoid secondary injuries caused by remaining wires which are permanently left in the body. The saTPW will provide a great platform for diagnosis and treatments in cardiovascular diseases by delivering the physiological signal and applying electrical stimulation for therapy.

The mitochondrial genome is widely used for phylogenetic analyses and evolutionary biology. The complete mitochondrial genome of Thitarodes sejilaensis (Lepidoptera: Hepialidae) was sequenced and analyzed in this study. This mitogenome is a typical circular molecule of 15,290bp, with the gene content, orientation and order identical to other insects in the family Hepialidae. The genome nucleotide composition is heavily biased towards As and Ts, accounting for 80.87% of total nucleotide content. The major strand shows a positive AT-skew and negative GC-skew. All 13 protein-coding genes (PCG) are initiated by the canonical putative start codons ATN, except for COI and ND1 that use the initiation codons CGA and TTG, respectively. Nine PCGs share the complete termination codons TAA, while the remaining PCGs use an incomplete termination codon T. Additionally, the codon distribution and Relative Synonymous Codon Usage of all PCGs in the T. sejilaensis mitogenome are consistent with other Hepialidae mitogenomes. Among 22 transfer RNAs, 21 have the typical clover-leaf structure, while tRNASer(AGN) does not possess the dihydrouridine (DHU) arm and could not form a stable stem-loop structure. The secondary structures of 2 ribosomal RNA genes broadly conform to the proposed models of these genes documented in other lepidopteran insects. T. sejilaensis AT-rich region exhibits three repetitive sequences of 118bp. Other regions contain 22-bp overlapping nucleotides and 72-bp intergenic nucleotides. The phylogenetic relationships were constructed by two datasets, the amino acid sequence derived from protein-coding genes and the nucleotide sequence of 13 PCGs and 2 rRNAs. Using Maximum Likelihood (ML), we reconstructed a phylogenetic tree which supported a more primitive taxa of Hepialoidea within Lepidoptera. Moreover, according to comparisons based on the CytB sequences and morphological characteristic, Hepialus species reported in China should be revised. Our taxonomic recommendations include assigning these species to the following genera: Thitarodes, Ahamus, Hepialus and Parahepialus.

Microfluidics, which enables manipulation of minute amount of fluids with nano-/micro-structures, has been applied in biomedical applications over past decades. This chapter will introduce several representative advancements in using microfluidics for cell manipulation and biochemical analysis.

Blattisocius Keegan is a genus of predatory mites in the family Blattisociidae, with potential utility as biological control agents. In the present study, Illumina HiSeq was used to sequence the complete mt genome of B. keegani Fox. The mt genome of B. keegani was a circular DNA molecule of 17,314 bp. With a 1,935 bp-long non-coding region, it is the second largest mt genome in Acari. All 37 genes expected to be present in a standard metazoan mitogenome were identified in this genome. Phylogenetic analyses of 28 additional species of Acari were then performed based on the mt genome. Bayesian inference (BI) and Maximum likelihood (ML) algorithm were used to analyse the sequence data. Compared with Limulus polyphemus, rearrangements of 34 genes and changes of three genes orientation (trnE, trnF and trnS1) in B. keegani were observed. Additionally, the gene order of the six mesostigmata mites used in the study showed a lack of conserved gene blocks. BI and ML trees based on 13 protein-coding genes suggested that B. keegani was clustered with E. nicholsi and P. persimilis into a Phytoseioidea branch, which was consistent with the traditional classifications result.

We develop a rapid and facile method to fabricate tubular scaffolds by a single-step rolling operation. With the aid of fibrin medical glue and a smooth expanded polytetrafluoroethylene (ePTFE) mandrel, we can wrap a piece of flat thin film into a three-dimensional (3D), multi-layered tubular structure with well-controlled diameter, wall thickness, and mechanical strength within 10 min. By patterning different cells in a pre-designed area on the film, after rolling, we can obtain blood vessel-mimicking tissues with well-arranged, multilayered 3D architectures within 70 min. Our strategy provides an excellent platform to rapidly fabricate tubular scaffolds essentially with no equipment and straightforward manipulations.

To evaluate the predictive significance of F-18 FDG PET/CT quantization parameters for progression-free survival (PFS) in patients with diffuse large B cell lymphoma (DLBCL) before chemotherapy.We conducted a retrospective study involving 60 patients with DLBCL between January 2010 and August 2014 who had undergone F-18 FDG PET/CT scan prior to treatment. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and number of enlarged lymph nodes (2 cm) were measured. The primary outcome measure was PFS. Spearman rank correlation analysis, univariate and multivariate Cox regression models, receiver operating characteristic (ROC) analysis, and Kaplan-Meir survival curves were used.Spearman analysis determined that the MTV and TLG values were positively related to Ann Arbor stage, National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, and lactate dehydrogenase (LDH) level. The number of enlarged lymph nodes was positively related only to LDH level. The SUVmax value and clinical characteristics were not related. Univariate Cox regression determined that the MTV and TLG values, number of enlarged lymph nodes, and NCCN-IPI score were predictive factors. Multivariate Cox regression determined that the MTV and TLG values and number of enlarged lymph nodes predicted PFS independently of the NCCN-IPI score. The SUVmax value was not predictive of PFS. According to the cut-off determined from ROC analysis, lower MTV and TLG values were highly predictive of favorable PFS.In contrast to SUVmax, the MTV and TLG may be significant prognostic markers for PFS in DLBCL.

In this work, 4-(p-hydroxybenzylidenehydrazino)-N-butyl-1,8-naphthalimide (1) has been designed and synthesized as a colorimetric and fluorescent dual-modal probe for F- . Compound 1 immediately detected inorganic fluoride salts using UV/vis absorption and fluorescence spectroscopy methods, and served as a 'naked-eye' indicator for F- with high selectivity and sensitivity. Both the absorption and fluorescence spectra show excellent linearity with the concentration of F- . Real-life applications demonstrated that our proposed analytical system provided a satisfactory method for the determination of F- . In addition, the reaction mechanism of deprotonation was confirmed by 1 H NMR.

A method is developed that can rapidly produce blood vessel-like structures by bonding cell-laden electrospinning (ES) films layer by layer using fibrin glue within 90 min. This strategy allows control of cell type, cell orientation, and material composition in separate layers. Furthermore, ES films with thicker fibers (polylactic-co-glycolic acid, fiber diameter: ≈3.7 µm) are used as cell-seeding layers to facilitate the cell in-growth; those with thinner fibers (polylactic acid, fiber diameter: ≈1.8 µm) are used as outer reinforcing layers to improve the mechanical strength and reduce the liquid leakage of the scaffold. Cells grow, proliferate, and migrate well in the multilayered structure. This design aims at a new type of blood vessel substitute with flexible control of parameters and implementation of functions.

In the past decade, a flurry of new blood cells separation methods based microfluidic chip technology has emerged to address clinical diagnosis and biological research. The crossflow-based filtration separation method, because of its simple working principle and effectively overcoming the chip clogging problem, is gradually developing as an attractive solution for blood cells separation. In order to investigate and optimize the structure of a crossflow-based separator for blood cells, we studied how the tilt angle of the micro branch channel in the pillar array affects the fluid partitioning of low Reynolds number using Lattice Boltzmann (LBM) method. The reliability of using LBM to solve the flow of fluid of low Reynolds number is validated by the simulation of Poiseuille flow, and then a model of the branch channel, which mainly focuses on 4 different tilt angle (30°, 45°, 60°, 90°), is built to simulate. For far upstream and downstream in the main channel, and downstream in the side branch array channels, the fluid velocity profiles are assumed to adopt those of unidirectional Poiseuille flow with prescribed flow rates. The results show that the angle of inclination, with other conditions constant, will significantly influence the partition of fluid in the main channel and side branch array channels. Generally the larger the tilt angle is, the larger the rate flow in the branch array channel is, or vice versa.

Binding to binding site clusters has yet to be characterized in depth, and the functional relevance of low-affinity clusters remains uncertain. We characterized transcription factor binding to low-affinity clusters in vitro and found that transcription factors can bind concurrently to overlapping sites, challenging the notion of binding exclusivity. Furthermore, small clusters with binding sites an order of magnitude lower in affinity give rise to high mean occupancies at physiologically-relevant transcription factor concentrations. To assess whether the observed in vitro occupancies translate to transcriptional activation in vivo, we tested low-affinity binding site clusters in a synthetic and native gene regulatory network in S. cerevisiae. In both systems, clusters of low-affinity binding sites generated transcriptional output comparable to single or even multiple consensus sites. This systematic characterization demonstrates that clusters of low-affinity binding sites achieve substantial occupancies, and that this occupancy can drive expression in eukaryotic promoters.