Uncertainties of predictions from temperature replica exchange simulations.

Parallel tempering molecular dynamics simulation, also known as temperature replica exchange simulation, is a popular enhanced sampling method used to study biomolecular systems. This method makes it possible to calculate the free energy differences between states of the system for a series of temperatures. We developed a method to easily calculate the errors (standard errors or confidence intervals) of these predictions using a modified version of our recently introduced JumpCount method. The number of transitions between states (e.g., protein folding events) is counted for each temperature. This number of transitions, together with the temperature, fully determines the value of the standard error or the confidence interval of the free energy difference. We also address the issue of convergence in the situation where all replicas start from one state by developing an estimator of the equilibrium constant from simulations that are not fully equilibrated. The prerequisite of the method is the Markovianity of the process studied.

Free Energy Differences from Molecular Simulations: Exact Confidence Intervals from Transition Counts.

Here, we demonstrate a method to estimate the uncertainty (confidence intervals and standard errors) of free energy differences calculated by molecular simulations. The widths of confidence intervals and standard errors can be calculated solely from temperature and the number of transitions between states. Uncertainty (95% confidence interval) lower than ±1 kcal/mol can be achieved by a simulation with four forward and four reverse transitions. For a two-state Markovian system, the confidence interval is exact, regardless the number of transitions.

SERS and advanced chemometrics - Utilization of Siamese neural network for picomolar identification of beta-lactam antibiotics resistance gene fragment.

The enormous development and expansion of antibiotic-resistant bacterial strains impel the intensive search for new methods for fast and reliable detection of antibiotic susceptibility markers. Here, we combined DNA-targeted surface functionalization, surface-enhanced Raman spectroscopy (SERS) measurements, and subsequent spectra processing by decision system (DS) for detection of a specific oligonucleotide (ODN) sequence identical to a fragment of blaNDM-1 gene, responsible for ß-lactam antibiotic resistance. The SERS signal was measured on plasmonic gold grating, functionalized with capture ODN, ensuring the binding of corresponded ODNs. Designed DS consists of a Siamese neural network (SNN) coupled with robust statistics and Bayes decision theory. The proposed approach allows manipulation with complex multicomponent samples and predefine the desired detection level of confidence and errors, automatically determining the number of required spectra and samples. In constant to commonly used classification-type SNN, our method was applied to analyze samples with compositions previously "unknown" to DS. The detection of targeted ODN was performed with ≥99% level of confidence up to 3 × 10-12 M limit on the background of 10-10 M concentration of similar but not targeted ODNs.

Silica Nanoparticles from Coir Pith Synthesized by Acidic Sol-Gel Method Improve Germination Economics.

Lignin is a natural biopolymer. A vibrant and rapid process in the synthesis of silica nanoparticles by consuming the lignin as a soft template was carefully studied. The extracted biopolymer from coir pith was employed as capping and stabilizing agents to fabricate the silica nanoparticles (nSi). The synthesized silica nanoparticles (nSi) were characterized by ultraviolet-visible (UV-Vis) spectrophotometry, X-ray diffraction analysis (XRD), Scanning Electron Microscope (SEM), Energy-Dispersive X-ray Analysis (EDAX), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FTIR). All the results obtained jointly and independently verified the formation of silica nanoparticles. In addition, EDAX analysis confirmed the high purity of the nSi composed only of Si and O, with no other impurities. XRD spectroscopy showed the characteristic diffraction peaks for nSi and confirmed the formation of an amorphous nature. The average size of nSi obtained is 18 nm. The surface charge and stability of nSi were analyzed by using the dynamic light scattering (DLS) and thus revealed that the nSi samples have a negative charge (-20.3 mV). In addition, the seed germination and the shoot and root formation on Vigna unguiculata were investigated by using the nSi. The results revealed that the application of nSi enhanced the germination in V. unguiculata. However, further research studies must be performed in order to determine the toxic effect of biogenic nSi before mass production and use of agricultural applications.

Porous Medium Equation in Graphene Oxide Membrane: Nonlinear Dependence of Permeability on Pressure Gradient Explained.

Membrane performance in gas separation is quantified by its selectivity, determined as a ratio of measured gas permeabilities of given gases at fixed pressure difference. In this manuscript a nonlinear dependence of gas permeability on pressure difference observed in the measurements of gas permeability of graphene oxide membrane on a manometric integral permeameter is reported. We show that after reasoned assumptions and simplifications in the mathematical description of the experiment, only static properties of any proposed governing equation can be studied, in order to analyze the permeation rate for different pressure differences. Porous Medium Equation is proposed as a suitable governing equation for the gas permeation, as it manages to predict a nonlinear behavior which is consistent with the measured data. A coefficient responsible for the nonlinearity, the polytropic exponent, is determined to be gas-specific-implications on selectivity are discussed, alongside possible hints to a deeper physical interpretation of its actual value.

Highly Hydrophobic Organosilane-Functionalized Cellulose: A Promising Filler for Thermoplastic Composites.

The aim of this work is to design and optimize the process of functionalization of cellulose fibers by organosilane functional groups using low-pressure microwave plasma discharge with hexamethyldisiloxane (HMDSO) precursor in order to prepare a compatible hydrophobic filler for composites with nonpolar thermoplastic matrices. Particular attention was paid to the study of agglomeration of cellulose fibers in the mixture with polypropylene. In our contribution, the dependence of the surface wettability on used process gas and treatment time was investigated. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were applied to characterize the surface morphology and chemical composition of the cellulose fibers. It was observed that the plasma treatment in oxygen process gas led to the functionalization of cellulose fibers by organosilane functional groups without degradation. In addition, the treated cellulose was highly hydrophobic with water contact angle up to 143°. The use of treated cellulose allowed to obtain a homogeneous mixture with polypropylene powder due to the significantly lower tendency of the functionalized cellulose fibers to agglomerate.

The surgical treatment of renal tumors - a 30-month evaluation of the post operative period at a secondary center. / Tratamiento quirúrgico de tumores renales- evaluación postoperatoria a 30 meses en un centro secundario.

OBJECTIVES: Our aim was to compare nephrectomies with kidney resections in terms of their influence on renal function and blood loss. We compared laparoscopic nephrectomies with open nephrectomies in terms of the length of the procedure and the hospital stay. METHODS: We retrospectively included patients who were operated for renal tumors (n=148) between January 2016 to July 2018 in a single secondary center. We considered the type of operation (nephrectomies versus kidney resections), the approach to the kidney (open or laparoscopic) and compared the following outcomes: the length of the operation, perioperative blood loss, the changes in hemoglobin concentrations, in creatinine levels and in the estimated glomerular filtration rate (eGFR). RESULTS: Kidney resections when compared to nephrectomies resulted in a significantly smaller decline in the estimated glomerular filtration rates (ß=38.78 ml/min;p<0.001). When compared to baseline values, there was a significant drop in the eGFR on both day 1 and 3-6 months after the operation in the nephrectomy group (p<0.001 for both intervals); this drop was not present in the resection group. The decline in hemoglobin levels was bigger in the resection than in the nephrectomy group. However, during a follow up evaluation 3-6 months after the procedures, the values did not differ between the groups. We then compared open nephrectomies with laparoscopic nephrectomies. Laparoscopy involved more time (ß=38.6 minutes; p<0.001), was used for early stage tumors and involved a shorter hospital stay (ß=3 days;p<0.001) in comparison to open surgeries. CONCLUSIONS: Data from our center confirmed the findings from other literature that nephron-sparing surgeries lead to a lower decline in kidney function than with nephrectomies. This benefit for kidney function also remained during the follow-up. When performing a nephrectomy, the laparoscopic approach offers a shorter hospital stay for the patient than with an open surgery.

OBJETIVOS: Nuestro objetivo fue comparar las nefrectomías en términos de resultados de función renal y perdida de sangre. Comparamos las nefrectomías laparoscópicas con las abiertas en términos de duración de la cirugía y estancia hospitalaria. MÉTODOS: Se incluyeron retrospectivamente pacientes que fueron operados por tumores renales (n=148) entre enero 2016 y julio 2018 en un único centro secundario. Consideramos el tipo de cirugía (nefrectomía vs resección renal), la técnica quirúrgica (abierta vs laparoscópica) y comparando sus resultados: tiempo de cirugía, perdida sanguínea, cambios en la concentración hemoglobina, niveles de creatinina y filtrado glomerular estimado. RESULTADOS: Las resecciones renales en comparación con las nefrectomías presentaron una caída estimada de FG menor (ß=38,78 ml/min; p<0,001). Al comparar con los valores basales, se mostro una caída significativa de FG en los días 1 y a los 3-6 meses después de la operación en el grupo nefrectomía (p<0,001 en ambos intervalos); esta caída no estaba presente en el grupo de resección renal. La caída de hemoglobina fue superior en las resecciones renales en comparación con las nefrectomías. Aunque durante el seguimiento de 3 a 6 meses después del procedimiento, el valor no cambio entre grupos. Comparamos también las nefrectomías abiertas con laparoscópicas. Las laparoscópicas implican más tiempo (ß=38,6 minutos; p<0,001), se usaron en estadíos más precoces e implicaron menos estancia hospitalaria en comparación con las abiertas (ß=3 días; p<0,00). CONCLUSIONES: Los datos de nuestro centro confirmanlos hallazgos que la cirugía de resección renal implica menos caída de FG que las nefrectomías. Este beneficio se mantuvo en el seguimiento. Cuando realizamos una nefrectomía, la laparoscopia aporta una menor estancia hospitalaria que la cirugía abierta.

The surgical treatment of renal tumors a 30 month evaluation of the post operative period at a secondary center / El tratamiento quirúrgico de los tumores renales: una evaluación de 30 meses del período postoperatorio en un centro secundario

Objetives: Our aim was to comparenephrectomies with kidney resections in terms of their influence on renal function and blood loss. We comparedlaparoscopic nephrectomies with open nephrectomiesin terms of the length of the procedure and the hospitalstay.Mmethods: We retrospectively included patients whowere operated for renal tumors (n=148) between January 2016 to July 2018 in a single secondary center. Weconsidered the type of operation (nephrectomies versuskidney resections), the approach to the kidney (open orlaparoscopic) and compared the following outcomes:the length of the operation, perioperative blood loss, thechanges in hemoglobin concentrations, in creatinine levels and in the estimated glomerular filtration rate (eGFR). Results: Kidney resections when compared to nephrectomies resulted in a significantly smaller decline in theestimated glomerular filtration rates (β=38.78 ml/min;p<0.001). When compared to baseline values, therewas a significant drop in the eGFR on both day 1 and3-6 months after the operation in the nephrectomy group(p<0.001 for both intervals); this drop was not presentin the resection group. The decline in hemoglobin levels was bigger in the resection than in the nephrectomy group. However, during a follow up evaluation 3-6months after the procedures, the values did not differbetween the groups.We then compared open nephrectomies with laparoscopic nephrectomies. Laparoscopy involved more time(β=38.6 minutes; p<0.001), was used for early stagetumors and involved a shorter hospital stay (β=3 days;p<0.001) in comparison to open surgeries.Conclusions: Data from our center confirmed thefindings from other literature that nephron-sparing surgeries lead to a lower decline in kidney function thanwith nephrectomies. This benefit for kidney function alsoremained during the follow-up. When performing...(AU)

Objetivos: Nuestro objetivo fue comparar las nefrectomías en términos de resultados de funciónrenal y perdida de sangre. Comparamos las nefrectomías laparoscópicas con las abiertas en términos deduración de la cirugía y estancia hospitalaria. Métodos: Se incluyeron retrospectivamente pacientes que fueron operados por tumores renales (n=148)entre enero 2016 y julio 2018 en un único centrosecundario. Consideramos el tipo de cirugía (nefrectomía vs resección renal), la técnica quirúrgica (abierta vs laparoscópica) y comparando sus resultados: tiempo de cirugía, perdida sanguínea, cambios en laconcentración hemoglobina, niveles de creatinina y filtrado glomerular estimado.Resultados: Las resecciones renales en comparación con las nefrectomías presentaron una caída estimada de FG menor (β=38,78 ml/min; p<0,001).Al comparar con los valores basales, se mostro unacaída significativa de FG en los días 1 y a los 3-6 meses después de la operación en el grupo nefrectomía(p<0,001 en ambos intervalos); esta caída no estabapresente en el grupo de resección renal. La caída dehemoglobina fue superior en las resecciones renalesen comparación con las nefrectomías. Aunque durante el seguimiento de 3 a 6 meses después del procedimiento, el valor no cambio entre grupos.Comparamos también las nefrectomías abiertas conlaparoscópicas. Las laparoscópicas implican mástiempo (β=38,6 minutos; p<0,001), se usaron en estadios más precoces e implicaron menos estancia hospitalaria en comparación con las abiertas (β=3 días;p<0,001). Conclusiones: Los datos de nuestro centro confirman los hallazgos que la cirugía de resección renalimplica menos caída de FG que las nefrectomías.(AU)

Advanced Statistical Analysis of 3D Kinect Data: Mimetic Muscle Rehabilitation Following Head and Neck Surgeries Causing Facial Paresis.

An advanced statistical analysis of patients' faces after specific surgical procedures that temporarily negatively affect the patient's mimetic muscles is presented. For effective planning of rehabilitation, which typically lasts several months, it is crucial to correctly evaluate the improvement of the mimetic muscle function. The current way of describing the development of rehabilitation depends on the subjective opinion and expertise of the clinician and is not very precise concerning when the most common classification (House-Brackmann scale) is used. Our system is based on a stereovision Kinect camera and an advanced mathematical approach that objectively quantifies the mimetic muscle function independently of the clinician's opinion. To effectively deal with the complexity of the 3D camera input data and uncertainty of the evaluation process, we designed a three-stage data-analytic procedure combining the calculation of indicators determined by clinicians with advanced statistical methods including functional data analysis and ordinal (multiple) logistic regression. We worked with a dataset of 93 distinct patients and 122 sets of measurements. In comparison to the classification with the House-Brackmann scale the developed system is able to automatically monitor reinnervation of mimetic muscles giving us opportunity to discriminate even small improvements during the course of rehabilitation.

Time-Lagged t-Distributed Stochastic Neighbor Embedding (t-SNE) of Molecular Simulation Trajectories.

Molecular simulation trajectories represent high-dimensional data. Such data can be visualized by methods of dimensionality reduction. Non-linear dimensionality reduction methods are likely to be more efficient than linear ones due to the fact that motions of atoms are non-linear. Here we test a popular non-linear t-distributed Stochastic Neighbor Embedding (t-SNE) method on analysis of trajectories of 200 ns alanine dipeptide dynamics and 208 µs Trp-cage folding and unfolding. Furthermore, we introduce a time-lagged variant of t-SNE in order to focus on rarely occurring transitions in the molecular system. This time-lagged t-SNE efficiently separates states according to distance in time. Using this method it is possible to visualize key states of studied systems (e.g., unfolded and folded protein) as well as possible kinetic traps using a two-dimensional plot. Time-lagged t-SNE is a visualization method and other applications, such as clustering and free energy modeling, must be done with caution.

Chronological Age as Factor Influencing the Dental Implant Osseointegration in the Jaw Bone.

The objectives of this study were to evaluate osseointegration of dental implant in the jaw bone in the young and elderly population and comparing the results to assess indicators and risk factors as age for the success or failure of dental implants. A retrospective study of 107 implants (Impladent, LASAK, Czech Republic) was prepared. The patients at implants surgery were divided in three groups. The patients were followed-up for a 7-year period. We evaluated osseointegration from long term point of view as a change of marginal bone levels close to dental implant. Marginal bone levels were recorded and analysed with regard to different patient- and implant-related factors. An influence of chronological age on change of marginal bone levels during 6-year retrospective study vas evaluated. The study examined 47 patient charts and 107 implants from the Second Faculty of Medicine, Charles University and University Hospital Motol. We proved that young healthy patients with long bridges or Branemarks have the same progression of marginal bone levels changes. The chronological age hasn't therefore direct influence on the osseointegration from long term point of view. But we found that the length of dental suprastrucure-prosthetic construction negatively influences marginal bone changes, though these results weren't statistically significant. More extensive dental implant suprastrucure undergoes smaller osseointegration. On the other hand the length of dental suprastrucure (prosthetic construction) negatively influences dental osseointegration in both groups of patient.

Free-Energy Surface Prediction by Flying Gaussian Method: Multisystem Representation.

Flying Gaussian method simulates multiple replicas of the studied system and enhances sampling by disfavoring replicas to simultaneously sample similar states. The bias potential used for this enhancement is highly dynamic when looking at individual replica, which raises concerns about the accuracy of free-energy surfaces predicted by reweighing methods. Here we show that the bias potential can be considered as static when looking at the simulation from a multisystem perspective. We present two equations that can be used to predict the free-energy surface, and we demonstrate their convergence.

Multisystem altruistic metadynamics-Well-tempered variant.

Metadynamics method has been widely used to enhance sampling in molecular simulations. Its original form suffers two major drawbacks, poor convergence in complex (especially biomolecular) systems and its serial nature. The first drawback has been addressed by introduction of a convergent variant known as well-tempered metadynamics. The second was addressed by introduction of a parallel multisystem metadynamics referred to as altruistic metadynamics. Here, we combine both approaches into well-tempered altruistic metadynamics. We provide mathematical arguments and trial simulations to show that it accurately predicts free energy surfaces.

Distance associated heterophoria measured with polarized Cross test of MKH method and its relationship to refractive error and age.

PURPOSE: Due to the expansion of modern optotype liquid crystal display with the help of positive polarization, measurement of heterophorias (HTFs) by means of polarization, and thus partial dissociation of perceptions, has become more and more accessible. Our aims were to establish the prevalence of distance associated HTF by measuring with polarized Cross test of MKH [measuring and correcting methodology after H-J Haase] method and its association with age and refractive error in clinical population of wide age range. METHODS: A cross-sectional study was carried out with 170 clinical subjects aged 15-78 years with an average age of 40.7±16.62 years. All the participants had best-corrected visual acuity better than 20/25, stereopsis ≤60 second of arc, no heterotropia, not undergone vision therapy, and had no eye disease. The distance associated HTF was measured with the Cross test of the MKH methodology. The quantification of associated HTF was acquired by means of Risley rotary prism. RESULTS: The occurrence of distance associated HTF was found in 71.2% of participants. Of the total, 36.5% of the cases had esophoria (EP), 9.4% EP and hyperphoria, 10.6% exophoria (XP), 7.1% XP and hyperphoria, 7.6% hyperphoria, and 28.8% orthophoria. The mean distance horizontal associated HTF was +0.76±2.38 Δ. With EP, the mean value was +2.47±2.18 Δ, and with XP, -2.1±1.72 Δ. There was no correlation observed between the amount of distance associated HTF and age. There was no effect of the type and amount of a refractive error on the amount of distance associated HTF. CONCLUSION: A high occurrence of distance associated HTF was revealed while performing the polarized Cross test of MKH method. The relationship between the degree of associated HTF and refractive error and age was not proved.