Splitting statistical potentials into meaningful scoring functions: testing the prediction of near-native structures from decoy conformations

Background: Recent advances on high-throughput technologies have produced a vast amount of protein sequences, while the number of high-resolution structures has seen a limited increase. This has impelled the production of many strategies to built protein structures from its sequence, generating a considerable amount of alternative models. The selection of the closest model to the native conformation has thus become crucial for structure prediction. Several methods have been developed to score protein models by energies, knowledge-based potentials and combination of both.Results: Here, we present and demonstrate a theory to split the knowledge-based potentials in scoring terms biologically meaningful and to combine them in new scores to predict near-native structures. Our strategy allows circumventing the problem of defining the reference state. In this approach we give the proof for a simple and linear application that can be further improved by optimizing the combination of Zscores. Using the simplest composite score () we obtained predictions similar to state-of-the-art methods. Besides, our approach has the advantage of identifying the most relevant terms involved in the stability of the protein structure. Finally, we also use the composite Zscores to assess the conformation of models and to detect local errors.Conclusion: We have introduced a method to split knowledge-based potentials and to solve the problem of defining a reference state. The new scores have detected near-native structures as accurately as state-of-art methods and have been successful to identify wrongly modeled regions of many near-native conformations.

Characterization of myocardial deformation in patients with different etiologies of left ventricular hypertrophy by using strain distribution from Magnetic Resonance Imaging

Introducción y objetivos. Se ha señalado que, en la miocardiopatía hipertrófica (MCH), la desorganización de las fibras regionales da lugar a segmentos en los que la deformación es nula o está gravemente reducida, y que estos segmentos tienen una distribución no uniforme en el ventrículo izquierdo (VI). Esto contrasta con lo observado en otros tipos de hipertrofia como en el corazón de atleta o la hipertrofia ventricular izquierda hipertensiva (HVI-HT), en los que puede haber una deformación cardiaca anormal, pero nunca tan reducida como para que se observe ausencia de deformación. Así pues, proponemos el empleo de la distribución de los valores de strain para estudiar la deformación en la MCH. Métodos. Con el empleo de resonancia magnética marcada (tagged), reconstruimos la deformación sistólica del VI de 12 sujetos de control, 10 atletas, 12 pacientes con MCH y 10 pacientes con HVI-HT. La deformación se cuantificó con un algoritmo de registro no rígido y determinando los valores de strain sistólico máximo radial y circunferencial en 16 segmentos del VI. Resultados. Los pacientes con MCH presentaron unos valores medios de strain significativamente inferiores a los de los demás grupos. Sin embargo, aunque la deformación observada en los individuos sanos y en los pacientes con HVI-HT se concentraba alrededor del valor medio, en la MCH coexistían segmentos con contracción normal y segmentos con una deformación nula o significativamente reducida, con lo que se producía una mayor heterogeneidad de los valores de strain. Se observaron también algunos segmentos sin deformación incluso en ausencia de fibrosis o hipertrofia. Conclusiones. La distribución de strain caracteriza los patrones específicos de deformación miocárdica en pacientes con diferentes etiologías de la HVI. Los pacientes con MCH presentaron un valor medio de strain significativamente inferior, así como una mayor heterogeneidad de strain (en comparación con los controles, los atletas y los pacientes con HVI-HT), y tenían regiones sin deformación.

Acute life-threatening presentation of vitamin d deficiency rickets.

Context: Clinical manifestations of vitamin D deficiency rickets are widely described; however cardiorespiratory arrest is an extremely rare presentation. Objective: The aim of this paper is to present the symptoms of severe vitamin D deficiency rickets and to highlight the importance of vitamin D prophylaxis in infants. Results: We report a case of a 16-month-old infant who presented to emergency room with a stridor that evolved into a full cardiorespiratory arrest secondary to hypocalcemia. Medical history revealed that the infant was exclusively breastfed without vitamin D supplementation until the age of 10 months. Due to cultural habits, his diet was also grossly deficient in dairy products. Physical exam revealed clinical signs of rickets. Laboratory test showed severe hypocalcemia, elevated alkaline phosphatase, normal serum phosphorous, decreased 25(OH) cholecalciferol, increased intact parathyroid hormone level, and normal urine calcium excretion. The radiography of the wrist showed evidence of cupping, fraying, metaphyseal widening, and demineralization of the distal radial and ulnar metaphyses. The bone mineral density of the lumbar spine measured by dual x-ray absorptiometry showed a Z-score below -2 SD. His cardiorespiratory arrest secondary to hypocalcemia was therefore attributed to severe nutritional rickets. Conclusion: Vitamin D deficiency rickets can be life threatening. Vitamin D supplementation is therefore crucial, especially in breastfed infants and some ethnic minorities (dark-skinned people, poor sun exposure), more at risk for developing severe rickets if not supplemented.

Comparing deep sclerectomy with collagen implant to the new method of very deep sclerectomy with collagen implant: a single-masked randomized controlled trial.

AIM: To prospectively study the intraocular pressure (IOP) lowering effect and safety of the new method of very deep sclerectomy with collagen implant (VDSCI) compared with standard deep sclerectomy with collagen implant (DSCI). METHODS: The trial involved 50 eyes of 48 patients with medically uncontrolled primary and secondary open-angle glaucoma, randomized to undergo either VDSCI procedure (25 eyes) or DSCI procedure (25 eyes). Follow-up examinations were performed before surgery and after surgery at day 1, at week 1, at months 1, 2, 3, 6, 9, 12, 18, and 24 months. Ultrasound biomicroscopy was performed at 3 and 12 months. RESULTS: Mean follow-up period was 18.6+/-5.9 (VDSCI) and 18.9+/-3.6 (DSCI) months (P=NS). Mean preoperative IOP was 22.4+/-7.4 mm Hg for VDSCI and 20.4+/-4.4 mm Hg for DSCI eyes (P=NS). Mean postoperative IOP was 3.9+/-2.3 (VDSCI) and 6.3+/-4.3 (DSCI) (P<0.05) at day 1, and 12.2+/-3.9 (VDSCI) and 13.3+/-3.4 (DSCI) (P=NS) at month 24. At the last visit, the complete success rate (defined as an IOP of < or =18 mm Hg and a percentage drop of at least 20%, achieved without medication) was 57% in VDSCI and 62% in DSCI eyes (P=NS) ultrasound biomicroscopy at 12 months showed a mean volume of the subconjunctival filtering bleb of 3.9+/-4.2 mm3 (VDSCI) and 6.8+/-7.5 mm3 (DSCI) (P=0.426) and 5.2+/-3.6 mm3 (VDSCI) and 5.4+/-2.9 mm3 (DSCI) (P=0.902) for the intrascleral space. CONCLUSIONS: Very deep sclerectomy seems to provide stable and good control of IOP at 2 years of follow-up with few postoperative complications similar to standard deep sclerectomy with the collagen implant.

Bilateral renal artery entrapment by diaphragmatic crura: a rare cause of renovascular hypertension with a specific management.

We present the case of a young man with compression of both renal arteries by the crura of the diaphragm. Correct diagnosis of renal artery entrapment is difficult but crucial. The investigations rely on an high index of suspicion and include Doppler ultrasound and spiral computed tomography angiography, which permits visualization of the diaphragm and its relationships with the aorta. This pathology, unlike common renal artery stenoses, requires surgical decompression and sometimes aortorenal bypass graft.

Rate of development of forensically-important Dipterain southern Brazil

Dipteran larvae were collected from rabbit (Oryctolagus cunniculus L.) carcasses during the four seasons in 2005 in the southernmost state of Rio Grande do Sul, Brazil. The larvae were fed ground beef at ambient temperatures following collection from carcasses. The development of each species under these conditions was estimated. The most abundant species in the carcasses were Lucilia eximia (Wiedemann) and Chrysomya albiceps (Wiedemann) (Calliphoridae), and they were found in all seasons. The data were fitted to a linear model that describes the relationship between temperature and linear developmental rating. These two species are primary forensic indicators in southern Brazil. Other species such as Hemilucilia semidiaphana (Rondani) (Calliphoridae), Synthesiomyia nudiseta (Wulp), Muscina stabulans (Fallen) (Muscidae), and Fannia pusio (Wiedemann) (Fanniidae) were forensically less important because they only occurred in high frequency in certain seasons and during the first days of carcass decomposition.

Biomass estimation of Triplectides egleri Sattler (Trichoptera, Leptoceridae) in a stream at Ducke Reserve, Central Amazonia

ABSTRACT Biomass is a fundamental measure for understanding the structure and functioning (e.g. fluxes of energy and nutrients in the food chain) of aquatic ecosystems. We aim to provide predictive models to estimate the biomass of Triplectides egleri Sattler, 1963, in a stream in Central Amazonia, based on body and case dimensions. We used body length, head-capsule width, interocular distance and case length and width to derive biomass estimations. Linear, exponential and power regression models were used to assess the relationship between biomass and body or case dimensions. All regression models used in the biomass estimation of T. egleri were significant. The best fit between biomass and body or case dimensions was obtained using the power model, followed by the exponential and linear models. Body length provided the best estimate of biomass. However, the dimensions of sclerotized structures (interocular distance and head-capsule width) also provided good biomass predictions, and may be useful in estimating biomass of preserved and/or damaged material. Case width was the dimension of the case that provided the best estimate of biomass. Despite the low relation, case width may be useful in studies that require low stress on individuals.

Homotopy Batalin-Vilkovisky algebras

This paper provides an explicit cofibrant resolution of the operad encoding Batalin-Vilkovisky algebras. Thus it defines the notion of homotopy Batalin-Vilkovisky algebras with the required homotopy properties. To define this resolution we extend the theory of Koszul duality to operads and properads that are defind by quadratic and linear relations. The operad encoding Batalin-Vilkovisky algebras is shown to be Koszul in this sense. This allows us to prove a Poincare-Birkhoff-Witt Theorem for such an operad and to give an explicit small quasi-free resolution for it. This particular resolution enables us to describe the deformation theory and homotopy theory of BV-algebras and of homotopy BV-algebras. We show that any topological conformal field theory carries a homotopy BV-algebra structure which lifts the BV-algebra structure on homology. The same result is proved for the singular chain complex of the double loop space of a topological space endowed with an action of the circle. We also prove the cyclic Deligne conjecture with this cofibrant resolution of the operad BV. We develop the general obstruction theory for algebras over the Koszul resolution of a properad and apply it to extend a conjecture of Lian-Zuckerman, showing that certain vertex algebras have an explicit homotopy BV-algebra structure.

Termination of Atrial Fibrillation by Catheter Ablation can be Successfully Predicted from Baseline ECG

Purpose Multiple organization indices (OIs) have been used to predict the outcome of stepwise catheter ablation (step-CA) in long-standing persistent AF (pers-AF), however with limited success. Our study aims at developing innovative OIs from baseline (BL, before ablation) ECG in order to predict the outcome of step-CA. Methods Fourteen consecutive patients (pts) (60±5 y, AF duration 21±9 m) underwent a step-CA consisting in pulmonary veins isolation, left atrial (LA) defragmentation and linear ablations, and right atrial (RA) ablations if non terminated. Chest lead V6 was placed in the back (V6b). After QRST cancellation from chest leads V1 to V6b, two OIs were computed to quantify the harmonic components of ECG atrial activity: 1) phase difference variance (PD) between the AF harmonic components as a measure of AF regularity, and 2) adaptive OI (AOI) evaluating the time evolution of the AF harmonic components. Both indices were compared to classical ones: a spectrum-based OI (SOI) and ECG AF cycle length (AFCL). Results Pers-AF was terminated into sinus rhythm or atrial tachycardia in 10/14 pts during step-CA, 8 during LA (LT), 2 during RA (RT) ablation, and 4 were non terminated (NT). The figure shows that LT was best separated from RT/NT before ablation by AOI computed on lead V1 (A) and PD from lead V6b (B) as compared to SOI and AFCL respectively. Conclusion Our results suggest that adaptive OIs computed before ablation perform better than classical OIs for separating LT from RT/NT pts. These findings are indicative of a higher baseline organization in LT pts that could be used to select candidates for the restoration of sinus rhythm by step-CA.

Validity of an arterial pressure waveform analysis device: does the puncture site play a role in the agreement with intermittent pulmonary artery catheter thermodilution measurements?

OBJECTIVE: The measurement of cardiac output is a key element in the assessment of cardiac function. Recently, a pulse contour analysis-based device without need for calibration became available (FloTrac/Vigileo, Edwards Lifescience, Irvine, CA). This study was conducted to determine if there is an impact of the arterial catheter site and to investigate the accuracy of this system when compared with the pulmonary artery catheter using the bolus thermodilution technique (PAC). DESIGN: Prospective study. SETTING: The operating room of 1 university hospital. PARTICIPANTS: Twenty patients undergoing cardiac surgery. INTERVENTIONS: CO was determined in parallel by the use of the Flotrac/Vigileo systems in the radial and femoral position (CO_rad and CO_fem) and by PAC as the reference method. Data triplets were recorded at defined time points. The primary endpoint was the comparison of CO_rad and CO_fem, and the secondary endpoint was the comparison with the PAC. MEASUREMENTS AND MAIN RESULTS: Seventy-eight simultaneous data recordings were obtained. The Bland-Altman analysis for CO_fem and CO_rad showed a bias of 0.46 L/min, precision was 0.85 L/min, and the percentage error was 34%. The Bland-Altman analysis for CO_rad and PAC showed a bias of -0.35 L/min, the precision was 1.88 L/min, and the percentage error was 76%. The Bland-Altman analysis for CO_fem and PAC showed a bias of 0.11 L/min, the precision was 1.8 L/min, and the percentage error was 69%. CONCLUSION: The FloTrac/Vigileo system was shown to not produce exactly the same CO data when used in radial and femoral arteries, even though the percentage error was close to the clinically acceptable range. Thus, the impact of the introduction site of the arterial catheter is not negligible. The agreement with thermodilution was low.

A Laboratory Investigation into the Effects of the Aggregated Related Facts of Critical VMA in Asphalt Paving Mixtures, June 2000

This report summarizes research conducted at Iowa State University on behalf of the Iowa Department of Transportation, focusing on the volumetric state of hot-mix asphalt (HMA) mixtures as they transition from stable to unstable configurations. This has raditionally been addressed during mix design by meeting a minimum voids in the mineral aggregate (VMA) requirement, based solely upon the nominal maximum aggregate size without regard to other significant aggregate-related properties. The goal was to expand the current specification to include additional aggregate properties, e.g., fineness modulus, percent crushed fine and coarse aggregate, and their interactions. The work was accomplished in three phases: a literature review, extensive laboratory testing, and statistical analysis of test results. The literature review focused on the history and development of the current specification, laboratory methods of identifying critical mixtures, and the effects of other aggregate-related factors on critical mixtures. The laboratory testing involved three maximum aggregate sizes (19.0, 12.5, and 9.5 millimeters), three gradations (coarse, fine, and dense), and combinations of natural and manufactured coarse and fine aggregates. Specimens were compacted using the Superpave Gyratory Compactor (SGC), conventionally tested for bulk and maximum theoretical specific gravities and physically tested using the Nottingham Asphalt Tester (NAT) under a repeated load confined configuration to identify the transition state from sound to unsound. The statistical analysis involved using ANOVA and linear regression to examine the effects of identified aggregate factors on critical state transitions in asphalt paving mixtures and to develop predictive equations. The results clearly demonstrate that the volumetric conditions of an HMA mixture at the stable unstable threshold are influenced by a composite measure of the maximum aggregate size and gradation and by aggregate shape and texture. The currently defined VMA criterion, while significant, is seen to be insufficient by itself to correctly differentiate sound from unsound mixtures. Under current specifications, many otherwise sound mixtures are subject to rejection solely on the basis of failing to meet the VMA requirement. Based on the laboratory data and statistical analysis, a new paradigm to volumetric mix design is proposed that explicitly accounts for aggregate factors (gradation, shape, and texture).

Structural quality of a no-tillage red latosol 50 months after gypsum aplication

Gypsum application may enhance the soil quality for plants in terms of soil chemical and physical properties. The objective of this study was to evaluate the effects of gypsum application on the structural quality of a no-tillage Red Latosol. The experiment was initiated in September 2005 in Guarapuava-PR, with gypsum applications of 0; 4; 8; and 12 Mg ha-1 on the soil surface. In November 2009, two soil blocks were sampled from the 0-0.3 m layer for visual evaluation of the soil structure quality (Sq) and to determine the aggregate-tensile strength (ATS). Soil penetration resistance (PR) and gravimetric moisture (H%) of the 0-0.300 m layer were evaluated, and soil cores were collected (layers 0.000-0.075 and 0.075-0.150 m), to determine soil bulk density (BD), total soil porosity (TP), microporosity (Mi), and macroporosity (Ma). Data were subjected to analysis of regression at 5 %. No significant effects of gypsum application on ATS and H % of aggregates were observed, but for Sq, a quadratic effect (0.000-0.075 m) and linear increase (0.075-0.150 and 0.150-0.300 m) were stated, indicating soil quality decrease, although Sq remained mostly below 3.0, with good to intermediate soil quality. Soil PR increased with gypsum, but also remained below critical levels. No effect was observed for soil H % at the moment of PR determination on the field. The gypsum applications decreased BD in the 0.075-0.150 m layer, and increased PT and Ma, while in 0.000-0.075 m some Ma was converted to Mi, without affecting PT and BD. These last results indicate a gain in soil structural quality by gypsum applications, but the higher scores of soil structure and values of soil penetration resistance, though still below thresholds, should be monitored to prevent limitations to soil use in the future.

Performance of a reciprocal shaker in mechanical dispersion of soil samples for particle-size analysis

The dispersion of the samples in soil particle-size analysis is a fundamental step, which is commonly achieved with a combination of chemical agents and mechanical agitation. The purpose of this study was to evaluate the efficiency of a low-speed reciprocal shaker for the mechanical dispersion of soil samples of different textural classes. The particle size of 61 soil samples was analyzed in four replications, using the pipette method to determine the clay fraction and sieving to determine coarse, fine and total sand fractions. The silt content was obtained by difference. To evaluate the performance, the results of the reciprocal shaker (RSh) were compared with data of the same soil samples available in reports of the Proficiency testing for Soil Analysis Laboratories of the Agronomic Institute of Campinas (Prolab/IAC). The accuracy was analyzed based on the maximum and minimum values defining the confidence intervals for the particle-size fractions of each soil sample. Graphical indicators were also used for data comparison, based on dispersion and linear adjustment. The descriptive statistics indicated predominantly low variability in more than 90 % of the results for sand, medium-textured and clay samples, and for 68 % of the results for heavy clay samples, indicating satisfactory repeatability of measurements with the RSh. Medium variability was frequently associated with silt, followed by the fine sand fraction. The sensitivity analyses indicated an accuracy of 100 % for the three main separates (total sand, silt and clay), in all 52 samples of the textural classes heavy clay, clay and medium. For the nine sand soil samples, the average accuracy was 85.2 %; highest deviations were observed for the silt fraction. In relation to the linear adjustments, the correlation coefficients of 0.93 (silt) or > 0.93 (total sand and clay), as well as the differences between the angular coefficients and the unit < 0.16, indicated a high correlation between the reference data (Prolab/IAC) and results obtained with the RSh. In conclusion, the mechanical dispersion by the reciprocal shaker of soil samples of different textural classes was satisfactory. The results allowed recommending the use of the equipment at low agitation for particle size- analysis. The advantages of this Brazilian apparatus are its low cost, the possibility to simultaneously analyze a great number of samples using ordinary, easily replaceable glass or plastic bottles.

Generation of TALEN-mediated GRdim knock-in rats by homologous recombination.

Transcription Activator-Like Effector Nucleases (TALEN) are potential tools for precise genome engineering of laboratory animals. We report the first targeted genomic integration in the rat using TALENs (Transcription Activator-Like Effector Nucleases) by homology-derived recombination (HDR). We assembled TALENs and designed a linear donor insert targeting a pA476T mutation in the rat Glucocorticoid Receptor (Nr3c1) namely GR(dim), that prevents receptor homodimerization in the mouse. TALEN mRNA and linear double-stranded donor were microinjected into rat one-cell embryos. Overall, we observed targeted genomic modifications in 17% of the offspring, indicating high TALEN cutting efficiency in rat zygotes.

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness.

PURPOSE: Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment. METHODS: Prospective observational study in the medicosurgical ICU of a university teaching hospital. All consecutive patients staying ≥4 days were enrolled. Potential risk factors were recorded: pathology, energy intake, amount and type of nutritional lipids, intake of propofol, glucose intake, laboratory parameters, and drugs. Triglyceride (TG) levels were assessed three times weekly. Statistics was based on two-way analysis of variance (ANOVA) and linear regression with potential risk factors. RESULTS: Out of 1,301 consecutive admissions, 220 patients were eligible, of whom 99 (45 %) presented hyperTG (triglycerides >2 mmol/L). HyperTG patients were younger, heavier, with more brain injury and multiple trauma. Intake of propofol (mg/kg/h) and lipids' propofol had the highest correlation with plasma TG (r (2) = 0.28 and 0.26, respectively, both p < 0.001). Infection and inflammation were associated with development of hyperTG [C-reactive protein (CRP), r (2) = 0.19, p = 0.004]. No strong association could be found with nutritional lipids or other risk factors. Outcome was similar in normo- and hyperTG patients. CONCLUSIONS: HyperTG is frequent in the ICU but is not associated with adverse outcome. Propofol and accompanying lipid emulsion are the strongest risk factors. Our results suggest that plasma TG should be monitored at least twice weekly in patients on propofol. The clinical consequences of propofol-related hyperTG should be investigated in further studies.