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Nonparametric estimation for a probability density function that describes multivariate data has typically been addressed by kernel density estimation (KDE). A novel density estimator recently developed by Farmer and Jacobs offers an alternative high-throughput automated approach to univariate nonparametric density estimation based on maximum entropy and order statistics, improving accuracy over univariate KDE. This article presents an extension of the single variable case to multiple variables. The univariate estimator is used to recursively calculate a product array of one-dimensional conditional probabilities. In combination with interpolation methods, a complete joint probability density estimate is generated for multiple variables. Good accuracy and speed performance in synthetic data are demonstrated by a numerical study using known distributions over a range of sample sizes from 100 to 10 6 for two to six variables. Performance in terms of speed and accuracy is compared to KDE. The multivariate density estimate developed here tends to perform better as the number of samples and/or variables increases. As an example application, measurements are analyzed over five filters of photometric data from the Sloan Digital Sky Survey Data Release 17. The multivariate estimation is used to form the basis for a binary classifier that distinguishes quasars from galaxies and stars with up to 94% accuracy. [ABSTRACT FROM AUTHOR]

Abstract: To clarify the extent structure plays in determining protein dynamics, a comparative study is made using three models that characterize native state dynamics of single domain proteins starting from known structures taken from four distinct SCOP classifications. A geometrical simulation using the framework rigidity optimized dynamics algorithm (FRODA) based on rigid cluster decomposition is compared to the commonly employed elastic network model (specifically the Anisotropic Network Model ANM) and molecular dynamics (MD) simulation. The essential dynamics are quantified by a mode subspace constructed from ANM and a principal component analysis (PCA) on FRODA and MD trajectories. Aggregate conformational ensembles are constructed to provide a basis for quantitative comparisons between FRODA runs using different parameter settings to critically assess how the predictions of essential dynamics depend on a priori arbitrary user-defined distance constraint rules. We established a range of physicality for these parameters. Surprisingly, FRODA maintains greater intra-consistent results than obtained from MD trajectories, comparable to ANM. Additionally, a mode subspace is constructed from PCA on an exemplar set of myoglobin structures from the Protein Data Bank. Significant overlap across the three model subspaces and the experimentally derived subspace is found. While FRODA provides the most robust sampling and characterization of the native basin, all three models give similar dynamical information of a native state, further demonstrating that structure is the key determinant of dynamics. [Copyright &y& Elsevier]

A 47-year-old female with an occluded iliac vein stent originally placed for deep venous thrombosis and May-Thurner syndrome presented to our clinic with complaints of left lower extremity pain and swelling. Multiple previous attempts had been made to cross this lesion with guidewire and catheter techniques without success. We were able to cross the lesion with the Wildcat catheter. Subsequent directional laser atherectomy and balloon angioplasty followed by stent placement resulted in a patent stent and resolution of her symptoms. This is the first reported use of the Wildcat catheter in chronic venous stent occlusions. [ABSTRACT FROM PUBLISHER]

We compare various predicted mechanical and thermodynamic properties of nine oxidized thioredoxins (TRX) using a Distance Constraint Model (DCM). The DCM is based on a nonadditive free energy decomposition scheme, where entropic contributions are determined from rigidity and flexibility of structure based on distance constraints. We perform averages over an ensemble of constraint topologies to calculate several thermodynamic and mechanical response functions that together yield quantitative stability/flexibility relationships (QSFR). Applied to the TRX protein family, QSFR metrics display a rich variety of similarities and differences. In particular, backbone flexibility is well conserved across the family, whereas cooperativity correlation describing mechanical and thermodynamic couplings between the residue pairs exhibit distinctive features that readily standout. The diversity in predicted QSFR metrics that describe cooperativity correlation between pairs of residues is largely explained by a global flexibility order parameter describing the amount of intrinsic flexibility within the protein. A free energy landscape is calculated as a function of the flexibility order parameter, and key values are determined where the native-state, transition-state, and unfolded-state are located. Another key value identifies a mechanical transition where the global nature of the protein changes from flexible to rigid. The key values of the flexibility order parameter help characterize how mechanical and thermodynamic response is linked. Variation in QSFR metrics and key characteristics of global flexibility are related to the native state X-ray crystal structure primarily through the hydrogen bond network. Furthermore, comparison of three TRX redox pairs reveals differences in thermodynamic response (i.e., relative melting point) and mechanical properties (i.e., backbone flexibility and cooperativity correlation) that are consistent with experimental data on thermal stabilities and NMR dynamical profiles. The results taken together demonstrate that small-scale structural variations are amplified into discernible global differences by propagating mechanical couplings through the H-bond network. Proteins 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

How can an income tax system be designed to exploit human nature and a free market to create a poverty free society, while balancing budgets without disproportional tax burdens? Such a tax system, with universal character, is deduced from the following guiding principles: (1) a single tax rate applies to all income types and levels; (2) the tax rate adjusts to satisfy budget projections; (3) government transfer only supplements the income of households with self-generated income below the poverty line; (4) deductions for basic living expenses, itemized investments and capital losses are allowed; (5) deductions cannot be applied to government transfer. A general framework emerges with three parameters that determine a minimum allowed tax deduction, a maximum allowed itemized deduction, and a maximum deduction defined by income percentage. An income distribution that mimics the United States, and a series of log-normal distributions are considered to quantitatively compare detailed characteristics of this tax system to progressive and flat tax systems. To minimize government dependency while maximizing after-tax income, the effective tax rate (ETR) as a function of income percentile takes the shape of the letter, V, inspiring the name victory tax, where the middle class has the lowest ETR. [ABSTRACT FROM AUTHOR]

Myosin is an actin-based motor protein that generates force by cycling between actin-attached (strong binding: ADP or rigor) and actin-detached (weak binding: ATP or ADP·Pi) states during its ATPase cycle. However, it remains unclear what specific conformational changes in the actin binding site take place on binding to actin, and how these structural changes lead to product release and the production of force and motion. We studied the dynamics of the actin binding region of myosin V by using fluorescence resonance energy transfer (FRET) to monitor conformational changes in the upper-50-kDa domain of the actin binding cleft in the weak and strong actin binding states. Steady-state and lifetime data monitoring the FRET signal suggest that the cleft is in a more open conformation in the weak actin binding states. Transient kinetic experiments suggest that a rapid conformational change occurs, which is consistent with cleft closure before actin-activated phosphate release. Our results have identified a pre-force-generation actomyosin ADP·Pi state, and suggest force generation may occur from a state not yet seen by crystallography in which the actin binding cleft and the nucleotide binding pocket are closed. Computational modeling uncovers dramatic changes in the rigidity of the upper-50-kDa domain in different nucleotide states, which suggests that the intrinsic flexibility of this domain allows myosin motors to accomplish simultaneous tight nucleotide binding (closed nucleotide binding pocket) and high-affinity actin binding (closed actin binding cleft). [ABSTRACT FROM AUTHOR]

Treatment of chronic total occlusions of the iliac and femoral-popliteal vessels with endovascular techniques has become the standard approach for shorter lesions and is increasingly applied to long, complex arterial occlusive lesions, As the complexity of the arterial occlusions increases, the demands for technical skills and devices needed to successfully cross and treat the occlusion also increases. We describe here our technique for treatment of iliac and femoralpopliteal occlusions. Important aspects of that that have allowed for a high technical success include (1) the use of hydrophilic wires and catheters to traverse occlusions in the subintimal plane, (2) femoral access with axially supported catheters or sheaths to apply the force needed for successful recanalization, and (3) the use of true lumen reentry devices when, after crossing the occlusion, the wire or catheter cannot be manipulated into the true lumen beyond the occlusion. [ABSTRACT FROM AUTHOR]

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Cancer results in a hypercoagulable state that is associated with both venous and arterial thromboses. However, little is known about the effects of acute limb ischemia (ALI) in this cohort of patients. In the present systematic review and meta-analysis, we analyzed the available clinical data on cancer and its association with ALI and evaluated the outcomes in these patients after a diagnosis of ALI. Three databases, including PubMed, EMBASE, and the Cochrane Library, were queried. Studies that met the inclusion criteria were included regardless of the publication year, language, sample size, or follow-up length. All the steps of the meta-analysis were conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and MOOSE (meta-analysis of observational studies in epidemiology) guidelines. Seven studies from 6222 references with a total of 2899 patients were included. Of the 2899 patients, 1195 (41%) had had a diagnosis of ALI before their cancer diagnosis, and 1704 (59%) had presented with ALI after a cancer diagnosis. Nearly three quarters of ALI events were among patients with cancer of the skin and soft tissue (19%), genitourinary (18%), lung (17%), and gastrointestinal (16%) systems. ALI recurrence was similar between the two groups, and major amputation was more likely in patients with a diagnosis of ALI after a cancer diagnosis (7.4% vs 4.6%; P <.01). The incidence of mortality at 1 year was significantly greater for patients with established cancer who had presented with ALI compared with the patients who had presented with ALI before a cancer diagnosis (50.6% vs 29.9%; P <.01). After adjusting for study variability using the random effects model, the mortality at 1 year for all patients was 52.3% (95% confidence interval, 37.7%-66.5%). No significant heterogeneity (P =.73) was found between the two groups of patients, which varied by the timing of the ALI diagnosis in relation to the cancer diagnosis. The 1-year mortality after the development of ALI in patients with cancer was >50%. For patients presenting with ALI of unclear etiology, the presence of an underlying cancer should be considered. [ABSTRACT FROM AUTHOR]

Instance matching is a key task in knowledge graph fusion, and it is critical to improving the efficiency of instance matching, given the increasing scale of knowledge graphs. Blocking algorithms selecting candidate instance pairs for comparison is one of the effective methods to achieve the goal. In this paper, we propose a novel blocking algorithm named MultiObJ, which constructs indexes for instances based on the Ordered Joint of Multiple Objects' features to limit the number of candidate instance pairs. Based on MultiObJ, we further propose a distributed framework named Follow-the-Regular-Leader Instance Matching (FTRLIM), which matches instances between large-scale knowledge graphs with approximately linear time complexity. FTRLIM has participated in OAEI 2019 and achieved the best matching quality with significantly efficiency. In this research, we construct three data collections based on a real-world large-scale knowledge graph. Experiment results on the constructed data collections and two real-world datasets indicate that MultiObJ and FTRLIM outperform other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

We study the emission of photons from germinating seeds using an experimental technique designed to detect light of extremely small intensity. We analyze the dark count signal without germinating seeds as well as the photon emission during the germination process. The technique of analysis adopted here, called diffusion entropy analysis (DEA) and originally designed to measure the temporal complexity of astrophysical, sociological and physiological processes, rests on Kolmogorov complexity. The updated version of DEA used in this paper is designed to determine if the signal complexity is generated either by non-ergodic crucial events with a non-stationary correlation function or by the infinite memory of a stationary but non-integrable correlation function or by a mixture of both processes. We find that dark count yields the ordinary scaling, thereby showing that no complexity of either kinds may occur without any seeds in the chamber. In the presence of seeds in the chamber anomalous scaling emerges, reminiscent of that found in neuro-physiological processes. However, this is a mixture of both processes and with the progress of germination the non-ergodic component tends to vanish and complexity becomes dominated by the stationary infinite memory. We illustrate some conjectures ranging from stress induced annihilation of crucial events to the emergence of quantum coherence. [ABSTRACT FROM AUTHOR]

Presents the results of a study which examined the achievement and affective consequences of a cooperative learning method on students in a private Christian elementary school. Use of a quasi-experimental/control group design; Student Teams-Achievement Divisions (STAD) format for cooperative learning; Benefits of cooperative learning as a teaching method.

By use of direct surgical procedures, including endarterectomy and patch angioplasty, the reconstructed profunda femoris artery has been employed to treat symptoms of claudication from femoral-popliteal occlusive disease and to facilitate healing of ampu tations that spare the knee joint. As the techniques of distal arterial bypass have become more sophisticated with improved long-term patency, the role of profun daplasty has changed.Sixty-eight reconstructions of the profunda femoris artery were reviewed for 51 patients with limb-threatening ischemia (69%), claudication (28%), or infected pros thetic vascular grafts (3%). Thirty-three (49%) of the limbs had undergone 73 prior arterial reconstructions. Forty-nine patients had inflow procedures performed at the time of the profundaplasty, and 13 had concomitant reconstruction of arterial outflow. In only 6 cases was the procedure an isolated profundaplasty. Successful profun daplasty was defined as primary patency of the vascular reconstruction.By life table analysis, revascularizations utilizing profundaplasty had a primary patency of 81% at one year, 64% at two years, and 54% at four years. The series achieved a limb salvage rate of 96% at four years.Isolated profundaplasty is seldom utilized to treat critical ischemia of the lower extremity. The current role of profundaplasty places the procedure as an important adjunct to achieve long-term limb salvage and patency of complex vascular reconstructions. [ABSTRACT FROM PUBLISHER]

Acute limb ischemia (ALI) carries significant overall morbidity and mortality. Pregnant and postpartum women are physiologically hypercoagulable, but little is known about the impact of ALI in this cohort of patients. The goal of this systematic review was to gather available data on diagnosis and treatment of ALI during pregnancy and the postpartum period. A systematic review of studies on patients with ALI during pregnancy and the puerperium was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases including PubMed MEDLINE, Embase, and Cochrane Library were queried. Manuscripts that provided data on diagnosis and treatment of ALI in pregnant and postpartum patients were included regardless of language or study design. Outcomes of interest included type of treatment for ALI (open and endovascular), morbidity, and mortality. Fourteen manuscripts of 6222 references were included with a total of 14 patients. The median age of patients was 31.5 years. Embolism, present in eight (57%) patients, was slightly more common than thrombosis. All patients had a pregnancy complication or concomitant medical condition that might have predisposed to arterial occlusion either directly or indirectly by leading to iatrogenic arterial injury; peripartum cardiomyopathy, the most common, occurred in six (43%) patients. Open surgery was the preferred treatment option in 11 (79%) patients, followed by anticoagulation alone. No endovascular procedures were described. One patient underwent major amputation on presentation, and an additional patient required major amputation for recurrent ALI. No deaths occurred. Twelve (86%) patients had complete recovery with no other ALI-associated sequelae. ALI is rare in pregnant and postpartum women despite their transient physiologic hypercoagulability and is almost uniformly associated with pregnancy complications. Open surgical revascularization or anticoagulation alone appears to have acceptable outcomes as most patients present with embolism or thrombosis without underlying systemic arterial disease. [ABSTRACT FROM AUTHOR]

The beta-lactamase enzyme provides effective resistance to beta-lactam antibiotics due to substrate recognition controlled by point mutations. Recently, extended-spectrum and inhibitor-resistant mutants have become a global health problem. Here, the functional dynamics that control substrate recognition in TEM beta-lactamase are investigated using all-atom molecular dynamics simulations. Comparisons are made between wild-type TEM-1 and TEM-2 and the extended-spectrum mutants TEM-10 and TEM-52, both in apo form and in complex with four different antibiotics (ampicillin, amoxicillin, cefotaxime and ceftazidime). Dynamic allostery is predicted based on a quasi-harmonic normal mode analysis using a perturbation scan. An allosteric mechanism known to inhibit enzymatic function in TEM beta-lactamase is identified, along with other allosteric binding targets. Mechanisms for substrate recognition are elucidated using multivariate comparative analysis of molecular dynamics trajectories to identify changes in dynamics resulting from point mutations and ligand binding, and the conserved dynamics, which are functionally important, are extracted as well. The results suggest that the H10-H11 loop (residues 214-221) is a secondary anchor for larger extended spectrum ligands, while the H9-H10 loop (residues 194-202) is distal from the active site and stabilizes the protein against structural changes. These secondary non-catalytically-active loops offer attractive targets for novel noncompetitive inhibitors of TEM beta-lactamase. [ABSTRACT FROM AUTHOR]

Previously, we developed a high throughput non-parametric maximum entropy method (PLOS ONE, 13(5): e0196937, 2018) that employs a log-likelihood scoring function to characterize uncertainty in trial probability density estimates through a scaled quantile residual (SQR). The SQR for the true probability density has universal sample size invariant properties equivalent to sampled uniform random data (SURD). Alternative scoring functions are considered that include the Anderson-Darling test. Scoring function effectiveness is evaluated using receiver operator characteristics to quantify efficacy in discriminating SURD from decoy-SURD, and by comparing overall performance characteristics during density estimation across a diverse test set of known probability distributions. [ABSTRACT FROM AUTHOR]

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216) [ABSTRACT FROM AUTHOR]