Number Of Intermediate States Research Articles

Effect of Spin-Dependent Short-Range Correlations on Nuclear Matrix Elements for Neutrinoless Double Beta Decay of 48Ca

Neutrinoless double beta decay is a pivotal weak nuclear process that holds the potential to unveil the Majorana nature of neutrinos and predict their absolute masses. In this study, we delve into examining the impact of spin-dependent short-range correlations (SRCs) on the nuclear matrix elements (NMEs) for the light neutrino-exchange mechanism in neutrinoless double beta (0νββ) decay of 48Ca, employing an extensive interacting nuclear shell model. All computations are performed employing the effective shell model Hamiltonian GXPF1A, encompassing the entire fp model space through the closure approximation. Our investigation examines the NMEs’ dependencies on factors such as the number of intermediate states, coupled spin-parity attributes of neutrons and protons, neutrino momentum, inter-nucleon separation, and closure energy. This scrutiny is performed with respect to both the conventional Jastrow-type approach of SRCs, employing various parameterizations, and the spin-dependent SRC paradigm. Our findings illuminate a discernible distinction in NMEs induced by spin-dependent SRCs, differing by approximately 10–20% from those computed through the conventional Jastrow-type SRCs, incorporating distinct parameterizations.

Estimating Sojourn Time and Transition between Clinical States of HIV Patients under ART Follow up in Namibia

Background: Sojourn time refers to the amount of time a HIV patient spends in each clinical state in a single stay before he/she makes a transition to another state. HIV can be broken down into a number of intermediate states, based on CD4 counts. The four states of the Markov process of HIV are commonly defined as: S1: CD4 count > 500 cells/microlitre of blood; S2: 350 < CD4 count ≤ 500 cells/microlitre of blood; S3: 200 < CD4 count ≤ 350 cells/microlitre of blood; S4: CD4 count ≤ 200 cells/microliter of blood.
 Aims: The aim of the study was to estimate sojourn and transition between clinical states of patients under ART in Namibia using homogenous semi-Markov processes, on data obtained from MoHSS.
 Methods: A retrospective study design was used to obtain data on 2422 patients who were observed 11028 times, during 2008 to 2017 follow up period. The four staged semi-Markov model was employed to estimate sojourn times and transition between clinical states.
 Results: Results indicates that 1637 (67.6%) were female and 785 (32.41%) were male .657(27.13%) patients started ART in state 1, 683(28.19%) patients started ART in state 2, 677(27.95%) patients started ART in state 3 and 405(16.72%) patients started ART in state 4, at treatment commencement (t = 0). As expected, the probabilities of transiting from good to worse states increased with time. After 6 months, the probabilities of transiting from state 1 to 3, and from state 1 to 4 are 0.023 and 0.004 respectively. Whereas after 12 months, the probabilities of transiting from state 1 to 3, and from state 1 to 4 are 0.059 and 0.010 respectively. As time increased the probabilities to remain in the same state is decreasing (probabilities of remaining in state 1 after 6, 12 and 18 months is 0.804, 0.698 and 0.633). Sojourn times for states 1, 2, 3 and 4 were 22, 8, 10 and 15 months respectively.
 Conclusions: Sojourn time is of interest in HIV modeling, as it gives a signal of how HIV is progressing. Longer sojourn times indicates slow HIV progression and shorter sojourn times indicates rapid HIV progression. As time increases, transition probabilities from good states to worse states increases.

Abstract 2115: Multicomponent epigenetic profiling of intermediate epithelial-to-mesenchymal states in triple negative breast cancer identifies distinct regulatory signatures

Abstract Epithelial-to-mesenchymal transition (EMT) is an early step in the invasion-metastasis cascade, involving cellular progression through a number of intermediate states through the transition. Due to difficulty in isolating cells with intermediate EMT phenotypes, it has been challenging to investigate their molecular characteristics. Here, we describe multicomponent epigenetic profiles of phenotypes across the EMT spectrum. Six single cell clones on different points of the EMT spectrum were isolated from SUM149 cells, a heterogeneous ER/PR negative inflammatory breast cancer line. Methylation (mC) and hydroxymethylation (hmC) of >860,000 CpGs sites were measured with tandem oxidative bisulfite treatment and Illumina EPIC arrays, global chromatin accessibility was determined using Assay for Transposase Accessible Chromatin (ATAC) seq, and gene expression was measured using RNA-seq. We observed distinct mC and hmC profiles of the EMT intermediate clones compared to clones at either the epithelial or mesenchymal extremes. Intermediate clones demonstrated 17,862 CpGs with significantly higher hmC and 7,903 CpGs with significant hypomethylation, compared to the distal clones (FDR < 0.01). CpGs with higher hmC were enriched in regulatory regions such as promoters (OR = 2.87, p < 0.001), while hypomethylated CpGs were enriched in regions within the gene bodies. High hmC included CpGs located in promoters of key epithelial genes CDH1 and OCLN. In addition, 1,653 differentially accessible chromatin regions from ATAC-seq also were identified in intermediate clones (FDR < 0.1). Differentially accessible regions in the intermediate clones were associated with extracellular matrix organization (q-val = 0.04) in Reactome Pathway analysis. Although a large proportion of differentially accessible regions where differential hmC and mC CpGs were enriched tracked to distal intergenic regions (30.8%) and introns (28.1%), we did not observe significant enrichment of differential cytosine modifications overlapping with the differentially accessible chromatin regions which indicates the importance of multicomponent measures of epigenetic states. In genes with differentially accessible regions and hydroxymethylated CpGs, intermediate clones showed higher gene expression than distal clones. In particular, RUNX3 was observed to harbor all differential chromatin accessibility, hmC and mC CpGs, in intermediate clones. There was a stronger correlation between hmC and gene expression for differentially hydroxymethylated CpGs within accessible regions (R = 0.54, p < 0.01) than within non-accessible regions (R = 0.45, p = 0.02). Our results indicate both shared and distinct epigenetic profiles on the EMT spectrum at the cytosine and chromatin level regulate EMT processes and may be targeted to prevent the progression of EMT. Citation Format: Min Kyung Lee, Meredith S. Brown, Owen M. Wilkins, Diwakar R. Pattabiraman, Brock C. Christensen. Multicomponent epigenetic profiling of intermediate epithelial-to-mesenchymal states in triple negative breast cancer identifies distinct regulatory signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2115.

Advanced temperature dependent statistical analysis of forming voltage distributions for three different HfO2-based RRAM technologies

In this work, voltage distributions of forming operations are analyzed by using an advanced statistical approach based on phase-type distributions (PHD). The experimental data were collected from batches of 128 HfO2-based RRAM devices integrated in 4-kbit arrays. Three different switching oxides, namely, polycrystalline HfO2, amorphous HfO2, and Al-doped HfO2, were tested in the temperature range from −40 to 150 °C. The variability of forming voltages has been usually studied by using the Weibull distribution (WD). However, the performance of the PHD analysis demonstrated its ability to better model this crucial operation. The capacity of the PHD to reproduce the experimental data has been validated by means of the Kolmogorov-Smirnov test, while the WD failed in many of the cases studied. In addition, PHD allows to extract information about intermediate probabilistic states that occur in the forming process and the transition probabilities between them; in this manner, we can deepen on the conductive filament formation physics. In particular, the number of intermediate states can be related to the device variability.

Assessment of Mixtures by Spectral Superposition. An Approach in the Field of Metabolomics.

A recent field of metabolomic applications is the analysis of mixtures, for example, in food science or the early recognition of diseases. Particularly in large-scale studies, the number of intermediate states or mixtures tends to expand significantly and in practice, a manual analysis is extremely difficult if not nearly impossible. In this study, we present a model in which the NMR spectra of mixtures are calculated based on the spectral superposition of corresponding pure samples. Instead of using real spectra, where chemical shifts may be influenced by matrix effects, the linear combination of reduced data (buckets) was applied for the calculation. Starting from a set of 262 hazelnut samples of five Eurasian countries we obtained more than 160 000 NMR spectra with mixed geographic origin. Using these as a basis we calculated assessment curves to estimate to which extent admixtures are recognized within a multivariate classification model. Subsequently the calculated data were compared with the measured spectra of tangible mixtures to validate and assess the suitability of this method. The calculated spectra are very similar to the acquired data, and the resulting deviations are on a similar scale to the errors of current metabolomic measurements. Thus, with a suitable sample basis, various different mixtures can be simulated and limitations of the model can be described. This approach reduces time and resource consumption and allows valid predictions based on calculated NMR spectra. In addition to the first example dealing with the admixtures classification of single commodity foods, this approach may also be applied to simulate metabolic progression in other areas.

Energy Efficiency and Renewable Energy Management with Multi-State Power-Down Systems

A power-down system has an on-state, an off-state, and a finite or infinite number of intermediate states. In the off-state, the system uses no energy and in the on-state energy it is used fully. Intermediate states consume only some fraction of energy but switching back to the on-state comes at a cost. Previous work has mainly focused on asymptotic results for systems with a large number of states. In contrast, the authors study problems with a few states as well as systems with one continuous state. Such systems play a role in energy-efficiency for information technology but are especially important in the management of renewable energy. The authors analyze power-down problems in the framework of online competitive analysis as to obtain performance guarantees in the absence of reliable forecasting. In a discrete case, the authors give detailed results for the case of three and five states, which corresponds to a system with on-off states and three additional intermediate states “power save”, “suspend”, and “hibernate”. The authors use a novel balancing technique to obtain optimally competitive solutions. With this, the authors show that the overall best competitive ratio for three-state systems is 9 5 and the authors obtain optimal ratios for various five state systems. For the continuous case, the authors develop various strategies, namely linear, optimal-following, progressive and exponential. The authors show that the best competitive strategies are those that follow the offline schedule in an accelerated manner. Strategy “progressive” consistently produces competitive ratios significantly better than 2.

Nuclear structure studies of double-charge-exchange Gamow-Teller strength

The double Gamow-Teller strength distributions in even-$A$ Calcium isotopes were calculated using the nuclear shell model by applying the single Gamow-Teller operator two times sequentially on the ground state of the parent nucleus. The number of intermediate states actually contributing to the results was determined. The sum rules for the double Gamow-Teller operator in the full calculation were approximately fulfilled. In the case that the symmetry is restored approximately by introducing degeneracies of the $f$-levels, and the $p$-levels in the $fp$-model space, the agreement with the sum rules was very close.

METHOD FOR PLANNING THE OPTIMAL TRAJECTORY OF A THREE-LINK MANIPULATOR IN TRIDIMENSIONAL SPACE WITH AN OBSTACLE

Objectives. The method for planning the optimal trajectory of a three-link manipulator with 7 degrees of mobility in a tridimensional space containing an obstacle specified by an array of points of three-dimensional space and represented in the form of a sphere is considered in the article. A literature review on the research problem indicates that universal methods for planning the trajectory of the manipulator's movement are faced with problems of operational low accuracy or the algorithm's large computational complexity. The aim of the study is to develop methods for planning the optimal trajectory of a three-link manipulator in a tridimensional space with an obstacle. Methods. The study was carried out using the method of iterative piecewise linear approximation of the trajectory of an anthropomorphic manipulator and the choice of the optimal displacement trajectory according to the criterion of energy efficiency. Results. The method for planning the optimal trajectory of a three-link manipulator with 7 degrees of mobility in a tridimensional space containing an obstacle specified by an array of points of three-dimensional space and represented in the form of a sphere is considered in the article. The task is reduced to finding the Euler angles of the manipulator engines in order to pass to the final position either directly or using the developed method of searching for intermediate positions to achieve the result. The choice of the optimal trajectory for the obstacle bypass is made using the criterion of minimisation of the manipulator power consumption for the continuous operation of the mobile manipulative or anthropomorphic robot in offline mode. Conclusion. The method of planning the optimal trajectory of a three-link manipulator with 7 degrees of mobility in a three-dimensional space containing an obstacle specified by an array of points and represented in the form of a sphere possesses flexibility, which is achieved by varying the input parameter. Its increase makes the manipulator's movement more angular by reducing the number of intermediate states, which reduces computational costs while increasing energy costs and reducing the movement speed. Conversely, decreasing the parameter reduces energy consumption and increases the speed, but also increases computational costs, as the number of intermediate states increases and the movement becomes smoother. However, in order to reduce the estimated time, it is assumed that parallel calculations are used in calculating the Euler angles for the engines during the movement between the intermediate points, which greatly speeds up the calculation process. With the value of h=0, the trajectory degenerates into a curve and the application of the proposed method is not justified.

Weighted Synapses Without Carry Operations for RRAM-Based Neuromorphic Systems.

The parallel updating scheme of RRAM-based analog neuromorphic systems based on sign stochastic gradient descent (SGD) can dramatically accelerate the training of neural networks. However, sign SGD can decrease accuracy. Also, some non-ideal factors of RRAM devices, such as intrinsic variations and the quantity of intermediate states, may significantly damage their convergence. In this paper, we analyzed the effects of these issues on the parallel updating scheme and found that it performed poorly on the task of MNIST recognition when the number of intermediate states was limited or the variation was too large. Thus, we propose a weighted synapse method to optimize the parallel updating scheme. Weighted synapses consist of major and minor synapses with different gain factors. Such a method can be widely used in RRAM-based analog neuromorphic systems to increase the number of equivalent intermediate states exponentially. The proposed method also generates a more suitable ΔW, diminishing the distortion caused by sign SGD. Unlike when several RRAM cells are combined to achieve higher resolution, there are no carry operations for weighted synapses, even if a saturation on the minor synapses occurs. The proposed method also simplifies the circuit overhead, rendering it highly suitable to the parallel updating scheme. With the aid of weighted synapses, convergence is highly optimized, and the error rate decreases significantly. Weighted synapses are also robust against the intrinsic variations of RRAM devices.

Peptide Self-Assembly Measured Using Fluorescence Correlation Spectroscopy.

Fluorescence correlation spectroscopy (FCS) is a flexible and powerful technique to measure the diffusion of fluorescently labeled particles. It has been important in examining a range of biological processes, from intracellular transport, to DNA hybridization. It is particularly suited to measuring the assembly of peptides, since peptides are often too small to be detected by standard light scattering methods, or may not contain aromatic amino acid residues, which limits the use of other spectroscopic techniques. In this protocol, we describe state-of-the-art sample preparation for Aβ1-42 peptide solutions and the measurement and analysis of the self-assembly of the peptide to form fibrils via a number of intermediate states using FCS.

Two-Color Laser Resonance Ionization Spectroscopy of Zirconium Atoms

We have performed two-color laser resonance ionization spectroscopy of zirconium atoms to measure the energies of excited states below the third ionization limit. The number of intermediate states that we observed is 19, and energies deduced from the experiments agree with previous data. Complex ionization spectra of the excited states were observed through the intermediate states. The values of the first, second, and third ionization limits were derived from the Rydberg series of the spectra with quantum defect theory.

Controlling Stochasticity in Epithelial-Mesenchymal Transition Through Multiple Intermediate Cellular States.

Epithelial-mesenchymal transition (EMT) is an instance of cellular plasticity that plays critical roles in development, regeneration and cancer progression. Recent studies indicate that the transition between epithelial and mesenchymal states is a multi-step and reversible process in which several intermediate phenotypes might coexist. These intermediate states correspond to various forms of stem-like cells in the EMT system, but the function of the multi-step transition or the multiple stem cell phenotypes is unclear. Here, we use mathematical models to show that multiple intermediate phenotypes in the EMT system help to attenuate the overall fluctuations of the cell population in terms of phenotypic compositions, thereby stabilizing a heterogeneous cell population in the EMT spectrum. We found that the ability of the system to attenuate noise on the intermediate states depends on the number of intermediate states, indicating the stem-cell population is more stable when it has more sub-states. Our study reveals a novel advantage of multiple intermediate EMT phenotypes in terms of systems design, and it sheds light on the general design principle of heterogeneous stem cell population.

Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors

Thermodynamic integration (TI) can provide accurate binding free energy insights in a lead optimization program, but its high computational expense has limited its usage. In the effort of developing an efficient and accurate TI protocol for FabI inhibitors lead optimization program, we carefully compared TI with different Amber molecular dynamics (MD) engines (sander and pmemd), MD simulation lengths, the number of intermediate states and transformation steps, and the Lennard-Jones and Coulomb Softcore potentials parameters in the one-step TI, using eleven benzimidazole inhibitors in complex with Francisella tularensis enoyl acyl reductase (FtFabI). To our knowledge, this is the first study to extensively test the new AMBER MD engine, pmemd, on TI and compare the parameters of the Softcore potentials in the one-step TI in a protein-ligand binding system. The best performing model, the one-step pmemd TI, using 6 intermediate states and 1 ns MD simulations, provides better agreement with experimental results (RMSD = 0.52 kcal/mol) than the best performing implicit solvent method, QM/MM-GBSA from our previous study (RMSD = 3.00 kcal/mol), while maintaining similar efficiency. Briefly, we show the optimized TI protocol to be highly accurate and affordable for the FtFabI system. This approach can be implemented in a larger scale benzimidazole scaffold lead optimization against FtFabI. Lastly, the TI results here also provide structure-activity relationship insights, and suggest the parahalogen in benzimidazole compounds might form a weak halogen bond with FabI, which is a well-known halogen bond favoring enzyme.

Enlightening the photoactive site of channelrhodopsin-2 by DNP-enhanced solid-state NMR spectroscopy

Channelrhodopsin-2 from Chlamydomonas reinhardtii is a light-gated ion channel. Over recent years, this ion channel has attracted considerable interest because of its unparalleled role in optogenetic applications. However, despite considerable efforts, an understanding of how molecular events during the photocycle, including the retinal trans-cis isomerization and the deprotonation/reprotonation of the Schiff base, are coupled to the channel-opening mechanism remains elusive. To elucidate this question, changes of conformation and configuration of several photocycle and conducting/nonconducting states need to be determined at atomic resolution. Here, we show that such data can be obtained by solid-state NMR enhanced by dynamic nuclear polarization applied to (15)N-labeled channelrhodopsin-2 carrying 14,15-(13)C2 retinal reconstituted into lipid bilayers. In its dark state, a pure all-trans retinal conformation with a stretched C14-C15 bond and a significant out-of-plane twist of the H-C14-C15-H dihedral angle could be observed. Using a combination of illumination, freezing, and thermal relaxation procedures, a number of intermediate states was generated and analyzed by DNP-enhanced solid-state NMR. Three distinct intermediates could be analyzed with high structural resolution: the early [Formula: see text] K-like state, the slowly decaying late intermediate [Formula: see text], and a third intermediate populated only under continuous illumination conditions. Our data provide novel insight into the photoactive site of channelrhodopsin-2 during the photocycle. They further show that DNP-enhanced solid-state NMR fills the gap for challenging membrane proteins between functional studies and X-ray-based structure analysis, which is required for resolving molecular mechanisms.

Stochastic kinetics on networks: when slow is fast.

Most chemical and biological processes can be viewed as reaction networks in which different pathways often compete kinetically for transformation of substrates into products. An enzymatic process is an example of such phenomena when biological catalysts create new routes for chemical reactions to proceed. It is typically assumed that the general process of product formation is governed by the pathway with the fastest kinetics at all time scales. In contrast to the expectation, here we show theoretically that at time scales sufficiently short, reactions are predominantly determined by the shortest pathway (in the number of intermediate states), regardless of the average turnover time associated with each pathway. This universal phenomenon is demonstrated by an explicit calculation for a system with two competing reversible (or irreversible) pathways. The time scales that characterize this regime and its relevance for single-molecule experimental studies are also discussed.

Mechanisms and topology determination of complex chemical and biological network systems from first-passage theoretical approach

The majority of chemical and biological processes can be viewed as complex networks of states connected by dynamic transitions. It is fundamentally important to determine the structure of these networks in order to fully understand the mechanisms of underlying processes. A new theoretical method of obtaining topologies and dynamic properties of complex networks, which utilizes a first-passage analysis, is developed. Our approach is based on a hypothesis that full temporal distributions of events between two arbitrary states contain full information on number of intermediate states, pathways, and transitions that lie between initial and final states. Several types of network systems are analyzed analytically and numerically. It is found that the approach is successful in determining structural and dynamic properties, providing a direct way of getting topology and mechanisms of general chemical network systems. The application of the method is illustrated on two examples of experimental studies of motor protein systems.

Reduced Dynamic Models in Epithelial Transport

Most models developed to represent transport across epithelia assume that the cell interior constitutes a homogeneous compartment, characterized by a single concentration value of the transported species. This conception differs significantly from the current view, in which the cellular compartment is regarded as a highly crowded media of marked structural heterogeneity. Can the finding of relatively simple dynamic properties of transport processes in epithelia be compatible with this complex structural conception of the cell interior? The purpose of this work is to contribute with one simple theoretical approach to answer this question. For this, the techniques of model reduction are utilized to obtain a two-state reduced model from more complex linear models of transcellular transport with a larger number of intermediate states. In these complex models, each state corresponds to the solute concentration in an intermediate intracellular compartment. In addition, the numerical studies reveal that it is possible to approximate a general two-state model under conditions where strict reduction of the complex models cannot be performed. These results contribute with arguments to reconcile the current conception of the cell interior as a highly complex medium with the finding of relatively simple dynamic properties of transport across epithelial cells.

Remodeling of the Folding Free Energy Landscape of Staphylococcal Nuclease by Cavity-Creating Mutations

The folding of staphylococcal nuclease (SNase) is known to proceed via a major intermediate in which the central OB subdomain is folded and the C-terminal helical subdomain is disordered. To identify the structural and energetic determinants of this folding free energy landscape, we have examined in detail, using high-pressure NMR, the consequences of cavity creating mutations in each of the two subdomains of an ultrastable SNase, Δ+PHS. The stabilizing mutations of Δ+PHS enhanced the population of the major folding intermediate. Cavity creation in two different regions of the Δ+PHS reference protein, despite equivalent effects on global stability, had very distinct consequences on the complexity of the folding free energy landscape. The L125A substitution in the C-terminal helix of Δ+PHS slightly suppressed the major intermediate and promoted an additional excited state involving disorder in the N-terminus, but otherwise decreased landscape heterogeneity with respect to the Δ+PHS background protein. The I92A substitution, located in the hydrophobic OB-fold core, had a much more profound effect, resulting in a significant increase in the number of intermediate states and implicating the entire protein structure. Denaturant (GuHCl) had very subtle and specific effects on the landscape, suppressing some states and favoring others, depending upon the mutational context. These results demonstrate that disrupting interactions in a region of the protein with highly cooperative, unfrustrated folding has very profound effects on the roughness of the folding landscape, whereas the effects are less pronounced for an energetically equivalent substitution in an already frustrated region.

An Engineered Disulfide Bond Reversibly Traps the IgE-Fc3–4 in a Closed, Nonreceptor Binding Conformation

IgE antibodies interact with the high affinity IgE Fc receptor, FcεRI, and activate inflammatory pathways associated with the allergic response. The IgE-Fc region, comprising the C-terminal domains of the IgE heavy chain, binds FcεRI and can adopt different conformations ranging from a closed form incompatible with receptor binding to an open, receptor-bound state. A number of intermediate states are also observed in different IgE-Fc crystal forms. To further explore this apparent IgE-Fc conformational flexibility and to potentially trap a closed, inactive state, we generated a series of disulfide bond mutants. Here we describe the structure and biochemical properties of an IgE-Fc mutant that is trapped in the closed, non-receptor binding state via an engineered disulfide at residue 335 (Cys-335). Reduction of the disulfide at Cys-335 restores the ability of IgE-Fc to bind to its high affinity receptor, FcεRIα. The structure of the Cys-335 mutant shows that its conformation is within the range of previously observed, closed form IgE-Fc structures and that it retains the hydrophobic pocket found in the hinge region of the closed conformation. Locking the IgE-Fc into the closed state with the Cys-335 mutation does not affect binding of two other IgE-Fc ligands, omalizumab and DARPin E2_79, demonstrating selective blocking of the high affinity receptor binding.

Cross sections for the reactionse+e−→K+K−π+π−,K+K−π0π0, andK+K−K+K−measured using initial-state radiation events

We study the processes e+e−→K+K−π+π−γ, K+K−π0π0γ, and K+K−K+K−γ, where the photon is radiated from the initial state. About 84 000, 8000, and 4200 fully reconstructed events, respectively, are selected from 454 fb−1 of BABAR data. The invariant mass of the hadronic final state defines the e+e− center-of-mass energy, so that the K+K−π+π−γ data can be compared with direct measurements of the e+e−→K+K−π+π− reaction. No direct measurements exist for the e+e−→K+K−π0π0 or e+e−→K+K−K+K− reactions, and we present an update of our previous result based on a data sample that is twice as large. Studying the structure of these events, we find contributions from a number of intermediate states and extract their cross sections. In particular, we perform a more detailed study of the e+e−→ϕ(1020)ππγ reaction and confirm the presence of the Y(2175) resonance in the ϕ(1020)f0(980) and K+K−f0(980) modes. In the charmonium region, we observe the J/ψ in all three final states and in several intermediate states, as well as the ψ(2S) in some modes, and measure the corresponding products of branching fraction and electron width.35 MoreReceived 15 March 2011DOI:https://doi.org/10.1103/PhysRevD.86.012008© 2012 American Physical Society