Root Mean Standard Deviation Research Articles

Antioxidant activity of Bougainvillea spectabilis ethanol extracts as an aryl hydrocarbon inhibitor

Background: Antioxidants overcome ageing processes and skin tissue damage caused by free radicals. The flavonoid contents of Bougainvillea spectabilis Willd contain hydroxyl groups attached to the carbon of the aromatic rings which makes them capable of catching free radicals and absorbing UV-A and UV-B. Objective: This study aimed to investigate the in silico antioxidant activities of various compounds contained in B. spectabilis Willd ethanol extracts compared to control. Method: The identification was carried out using GCMS methods and Molegro Virtual Docker. The molecular mechanics of scoring functions used in this study were the Rerank score, Root Mean Standard Deviation, and H Bond Result: p-Trimethylsylyoxylphenyl-(trimethylsilyoxy)trimethylsilyacrilate had a better bond than vitamin C used as the control and is smaller than BHF_401 (A) standard ligand, indicated by rerank scores of -92.6478, -76.0593, and -104.771. Conclusion: p-Trimethylsilyloxyphenyl-(trimethylsilyloxy)trimethylsilylacrylate had a better and more stable bond (rerank score: -92.6478) than the positive vitamin C control (76.0593).

Assessing dissolved oxygen dynamics in Pasig River, Philippines: A HEC-RAS modeling approach during the COVID-19 pandemic

Abstract The water quality in Pasig River has been impacted by urbanization, industrialization, and the pandemic conditions. This study involved comparative analysis of dissolved oxygen (DO) levels before and during the pandemic. Field measurements, including water temperature, salinity, and DO, were conducted during neap and spring tides. To further understand and simulate DO distribution, a one-dimensional mathematical model, specifically Hydrologic Engineering Center-River Analysis System, was employed. Results showed that DO increased during the pandemic, ranging from 3.26 to 7.25 and 1.08 to 5.69 mg/L during neap and spring tide. From the minimum standard DO level, out of eight stations, seven passed during neap tide, while one station passed during spring tide. Salinity levels were higher during spring tide, which may have affected the DO. Salt intrusion was evident until 4 km from the confluence. The hydraulic model yielded average water level differences of 5.1 and 8.3 cm during calibration and validation, respectively. The DO calibration and simulation exhibited very good statistical evaluation outcomes, with values of 0.9 for Nash-Sutcliffe Efficiency and 0.3 for Root Mean Standard Deviation Ratio. These findings hold significant potential for formulation of water quality enhancement plans and implementation of solid waste management and pollution policies.

Моделирование стока горных рек Илейского Алатау с применением модели HBV-light

The research aimed to evaluate the possibility of applying the HBV model for assessing the flow of the Ile Alatau Mountain Range rivers. The main part of the corresponding water resources forms on the northern slopes of the Ile Alatau making them a significant water balance and water supply factor for the major cities of Almaty, Kaskelen, Talgar, and Yesik. The article includes a brief description of the HBV model, as well as hydrometeorologicaland topographical inputs, and continues with the description of the flow simulation outputs for the rivers with the catchment area varying between 71-601 km2. For the periods of 2000-2016, the model parameters were calibrated using the GAP optimization algorithm. The model’s performance was evaluated based on several criteria: Nash-Sutcliffe Efficiency (NSE), Percent bias (PBIAS), and Root Mean Standard Deviation Ratio (RSR). The selection of optimal parameters allowed obtaining the following model efficiency values: 0.80-0.93 (as per NSE), -0.78 to -15.33% (as per PBIAS), and 0.27–0.80 (as per RSR). The calculated model efficiencies point to the sufficient correlation between the dynamics of the observed and simulated runoffs during the calibration period. The study likewise included the assessment of the HBV model applicability as a forecasting technique based on the ratio. The outcomes of that exercise confirmed the facility of using the model for predicting the runoff of the Kaskelen, Talgar, Ulken Almaty, and Kishi Almaty Rivers. Due to the fact that the observation data were available only for 2020, the HBV model parameters of all the studied rivers, except the Talgar River, underwent validation for the periods of 2017-2020. The calibrated and validated parameters of the obtained Ile Alatau Mountain River Model can be recommended for runoff modeling based on the HBV-light model as well as for runoff forecasting, namely for short- and medium-term water flow forecasts, with the exception of the Turgen, Prokhodnaya and Uzyn Kargaly River Basins.

A Modified SCS Curve Number Method for Temporally Varying Rainfall Excess Simulation

The SCS curve number (SCS-CN) method has gained widespread popularity for simulating rainfall excess in various rainfall events due to its simplicity and practicality. However, it possesses inherent structural issues that limit its performance in accurately simulating rainfall excess and infiltration over time. The objective of this study was to develop a modified CN method with temporally varying rainfall intensity (MCN-TVR) by combining a soil moisture accounting (SMA) based SCS-CN method with the SMA method in the Hydrologic Engineering Center’s Hydrologic Modeling System (HEC-HMS). In the MCN-TVR, the SMA-based SCS-CN method is utilized to simulate the cumulative rainfall excess and infiltration, while the SMA method in the HEC-HMS serves as an infiltration control function. A key advantage of the MCN-TVR is that it eliminates the need for additional input parameters by inherently linking the parameters in the two SMA-based methods. Sixteen hypothetical 24 h SCS Type II rainfall events with different soil types and five real rainfall events for the Rush River Watershed in North Dakota were used to assess the performances of the MCN-TVR method and the SMA-based SCS-CN method. In the hypothetical simulations, the rainfall excess simulated by the SMA-based SCS-CN and MCN-TVR models was compared to that simulated by a Green–Ampt model. Discrepancies were observed between the rainfall excess simulated by the SMA-based SCS-CN and Green–Ampt models, especially for coarse soils under relatively light rainfall. However, the MCN-TVR model, incorporating an infiltration control function, demonstrated its improved performance closer to the Green–Ampt model. For all the hypothetical events, the Nash–Sutcliffe efficiency (NSE) coefficient of the rainfall excess simulated by the MCN-TVR method compared to the Green–Ampt model was greater than 0.99, while the root mean standard deviation ratio (RSR) was less than 0.03. In the real applications, the SMA-based SCS-CN model failed to provide acceptable simulation of the direct runoff for rainfall events with durations of less than the time of concentration. In contrast, the MCN-TVR model successfully simulated the direct runoff for all the events with NSE values ranging from 0.65 to 0.91 and RSR values from 0.31 to 0.56.

Molecular docking and dynamics analysis of halogenated imidazole chalcone as anticancer compounds

Cancer is one of the three biggest causes of death in the world. The development of new drugs against this disease is a serious study that must be carried out in order to reduce mortality and extend the life span of sufferers. The aim of this research was to develop a new anti-cancer drug based on halogenated imidazole chalcones have been conducted. A 18 The halogenated imidazole chalcone compound was designed and performed molecular docking. Potential compounds of molecular docking are then carried out molecular dynamics. The results of molecular docking show that the potential chalcones based on bond affinity and specific interactions are chalcones B5, B6, C5, and C6. Analysis of the molecular dynamics result parameters are root mean standard deviation (RMSD) complex, root mean square fluctuation (RMSF), Radius of Gyration, Protein-ligand hydrogen bonding, and complex stability with generalized born surface area (GBSA) method, where the potential chalcone compounds are chalcones B5 and B6.

Abstract 5809: Tracking cancer stem cell expression of pancreatic and ampullary cancer organoids in response to chemotherapy

Abstract Background: Cancer stem cells (CSCs) have been described to confer resistance and aggressive disease biology in pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AMPC). Patient derived cancer organoids (PCOs) are an important model of PDAC that maintain the molecular features of advanced disease and have been shown to predict drug response. This study aimed to determine the dynamics of CSC expression on the oligoclonal culture growth of three independent PCOs models. Methods: PCOs were assayed using low volume 10μL microformat in 96 well design (Ibidi, Inc). PCOs were treated with physiologic FOLFIRINOX or gemcitabine + nab-paclitaxel (nab-pac) including single agent controls. Response was assayed by growth using timecourse data from 0h to 72h using high content imaging (Cytation 5). At 72h, the PCOs were stained using four distinct CSC markers (CD44, CD133, CD117, and EpCAM). Images were aligned using thresholded root mean standard deviation of 75μm and tracked for normalized change in longest diameter. At 72h, CSC markers were tracked using % area positive from brightfield region of interest. Response was tracked by effect size Glass’s Delta (GΔ) defined as the difference between the mean of media control and treatment group normalized to standard deviation of media control. Results: PCOs maintained nuclear atypia and high nuclear-chromatin ratios consistent with matured xenografts. AMPC1 showed similar sensitivity with growth arrest by PCO Δ diameter for gem + nab-pac (mean = +2.2%, GΔ = 1.29) and FOLFIRINOX (mean = 0.0%, GΔ = 1.33). AMPC1 had CSC enrichment for CD44 after treatment with nab-pac (GΔ = 0.93), CD133 expression after treatment with gem + nab-pac (GΔ = 0.75), CD117 after treatment with nab-pac treatment (GΔ = 0.80), and EpCAM after treatment with gem + nab-pac (GΔ = 0.78). In AMPC1, interquartile analysis revealed increased CSC expression conferred reduced growth for CD133 (+72% v. 37%, p<0.005) and CD117 (+81% v. +25%, p<0.005). Normalized Δ diameter across PDAC PCOs revealed PDAC1 had reduced sensitivity to gem + nab-pac (mean = +16.0%, GΔ = 1.2) vs. PDAC2 (Mean = 2.1%, GΔ = 1.65). PDAC1 had CSC enrichment with increased % area of CD44+ after treatment with gem + nab-pac (GΔ = 1.13). In PDAC2, interquartile analysis revealed increased CSC expression conferred decreased growth rate for CD133 (+65% v. +36%, p< 0.005) and CD117 (+75% v. +38%, p<0.005). Conclusions: PDAC and AMPC PCOs reveal oligoclonal expression of CSC markers within a population. Increased CSC expression for CD133 and CD117 within a population consistently revealed decreased growth within an organoid population. CSC expression (CD44, CD133, CD117, and EpCAM) was found to be enriched under therapeutic challenge with gem and nab-pac containing chemotherapy. This work supports the oligoclonal and dynamic nature of CSCs for pancreaticobiliary cancers in response to therapeutic challenge. Citation Format: Eleanor Riedl, Austin Stram, MD Shahadat Hossan, Ethan S. Lin, Luke Koeppel, Jamie Warner, Sam Lubner, Stephanie McGregor, Wei Zhang, Jeremy Kratz. Tracking cancer stem cell expression of pancreatic and ampullary cancer organoids in response to chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5809.

Spatial Alignment of Organoids Tracking Subclonal Chemotherapy Resistance in Pancreatic and Ampullary Cancer.

Pancreatic and ampullary cancers remain highly morbid diseases for which accurate clinical predictions are needed for precise therapeutic predictions. Patient-derived cancer organoids have been widely adopted; however, prior work has focused on well-level therapeutic sensitivity. To characterize individual oligoclonal units of therapeutic response, we introduce a low-volume screening assay, including an automated alignment algorithm. The oligoclonal growth response was compared against validated markers of response, including well-level viability and markers of single-cell viability. Line-specific sensitivities were compared with clinical outcomes. Automated alignment algorithms were generated to match organoids across time using coordinates across a single projection of Z-stacked images. After screening for baseline size (50 μm) and circularity (>0.4), the match efficiency was found to be optimized by accepting the diffusion thresholded with the root mean standard deviation of 75 μm. Validated well-level viability showed a limited correlation with the mean organoid size (R = 0.408), and a normalized growth assayed by normalized changes in area (R = 0.474) and area (R = 0.486). Subclonal populations were defined by both residual growth and the failure to induce apoptosis and necrosis. For a culture with clinical resistance to gemcitabine and nab-paclitaxel, while a therapeutic challenge induced a robust effect in inhibiting cell growth (GΔ = 1.53), residual oligoclonal populations were able to limit the effect on the ability to induce apoptosis (GΔ = 0.52) and cell necrosis (GΔ = 1.07). Bioengineered approaches are feasible to capture oligoclonal heterogeneity in organotypic cultures, integrating ongoing efforts for utilizing organoids across cancer types as integral biomarkers and in novel therapeutic development.

Piloting a training program in computed tomography skeletal muscle assessment for registered dietitians.

Consensus definitions for disease-associated malnutrition and sarcopenia include reduced skeletal muscle mass as a diagnostic criterion. There is a need to develop and validate techniques to assess skeletal muscle in clinical practice. Skeletal muscle mass can be precisely quantified from computed tomography (CT) images. This pilot study aimed to train registered dietitians (RDs) to complete precise skeletal muscle measurements using CT. Purposive sampling identified RDs employed in clinical areas in which CT scans are routinely performed. CT training included (1) a 3-Day training session focused on manual segmentation of skeletal muscle cross-sectional areas (cm2 , centimeter squared) from abdominal CT images at the third lumbar vertebra (L3), using sliceOmatic® software, and (2) a precision assessment to quantify the intraobserver and interobserver precision error of repeated skeletal muscle measurements (30 images in duplicate). Precision error is reported as the root mean standard deviation (cm2 ) and percent coefficient of variation (%CV), our primary performance indicator, was defined as a precision error of <2%. Five RDs completed CT training. RDs were from three clinical areas: cancer care (N = 1), surgery (N = 2), and critical care (N = 1). RDs' precision error was low and below the minimal acceptable error of <2%; intraobserver error was ≤1.8 cm2 (range, 0.8-1.8 cm2 ) or ≤1.5% (range, 0.8%-1.5%) and interobserver error was 1.2 cm2 or 1.1%. RDs can be trained to perform precise CT skeletal muscle measurements. Increasing capacity to assess skeletal muscle is a first step toward developing this technique for use in clinical practice.

Root Zone Soil Moisture Comparisons: AirMOSS, SMERGE, and SMAP

A long-standing goal in the terrestrial remote sensing community has been the development of a root-zone soil moisture (RZSM) product based on microwave radar or radiometry observations. For example, the National Aeronautics and Space Administration's (NASA's) Airborne Microwave Observatory of Subcanopy and Surface (AirMOSS) mission between 2012 and 2015 served as an airborne testbed for the development of RZSM estimates acquired from a 420-440 MHz (P-band) radar. Results from the AirMOSS mission suggest that P-band backscatter can be inverted to provide a direct measurement of 0- to 40-cm RZSM. However, whether AirMOSS RZSM is inherently more robust than indirect RZSM estimates including soil MERGE (SMERGE) and Soil Moisture Active Passive Level 4 (SMAP L4) is not clear. SMERGE and SMAP L4 leverage surface (2-5 cm depth), higher-frequency microwave observations (C- and L-bands) via data fusion (DFus) and data assimilation (DA) techniques, respectively. Therefore, the comparisons of these products are warranted and were based on bias, root mean square error (RMSE), and unbiased root mean standard deviation (ubRMSD) metrics. Comparisons also were made against in situ observations providing additional context. The seven AirMOSS sites within the contiguous United States (CONUS) were examined. Overall, direct AirMOSS RZSM measurements, based on the original retrieval algorithms, did not outperform indirect SMERGE and SMAP L4 RZSM estimates. These results provide insight into the viability of achieving enhanced RZSM accuracy via deployment of a spaceborne P-band radar.

Remote Sensing-Based Quantification of the Summer Maize Yield Gap Induced by Suboptimum Sowing Dates over North China Plain

Estimating yield potential (Yp) and quantifying the contribution of suboptimum field managements to the yield gap (Yg) of crops are important for improving crop yield effectively. However, achieving this goal on a regional scale remains difficult because of challenges in collecting field management information. In this study, we retrieved crop management information (i.e., emerging stage information and a surrogate of sowing date (SDT)) from a remote sensing (RS) vegetation index time series. Then, we developed a new approach to quantify maize Yp, total Yg, and the suboptimum SDT-induced Yg (Yg0) using a process-based RS-driven crop yield model for maize (PRYM–Maize), which was developed in our previous study. PRYM–Maize and the newly developed method were used over the North China Plain (NCP) to estimate Ya, Yp, Yg, and Yg0 of summer maize. Results showed that PRYM–Maize outputs reasonable estimates for maize yield over the NCP, with correlations and root mean standard deviation of 0.49 ± 0.24 and 0.88 ± 0.14 t hm−2, respectively, for modeled annual maize yields versus the reference value for each year over the period 2010 to 2015 on a city level. Yp estimated using our new method can reasonably capture the spatial variations in site-level estimates from crop growth models in previous literature. The mean annual regional Yp of 2010–2015 was estimated to be 11.99 t hm−2, and a Yg value of 5.4 t hm−2 was found between Yp and Ya on a regional scale. An estimated 29–42% of regional Yg in each year (2010–2015) was induced by suboptimum SDT. Results also show that not all Yg0 was persistent over time. Future studies using high spatial-resolution RS images to disaggregate Yg0 into persistent and non-persistent components on a small scale are required to increase maize yield over the NCP.

Experimental and numerical analysis of a packed-bed thermal energy storage system designed to recover high temperature waste heat: an industrial scale up

Abstract An industrial-scale air-ceramic horizontal packed-bed thermal energy storage (Eco-Stock®) has been designed and built by Eco-Tech Ceram and tested during an experimental campaign of 500h. The goal is to provide experimental data and analysis of a horizontal and containerized packed bed TES at high temperature, with performance indicators specific to waste heat recovery. A single charge-discharge at 525°C and 3 cycles at 500°C were carried out (300 kWTh for charge, 350 kWTh for discharge). The unit was able to store up to 1.9 MWhTh in a TES system (1.7 × 1.7 × 3.08 m3) composed by 16-ton of bauxite ceramic media. The packed bed was able to valorize up to 90% of the heat source, which demonstrates the system ability to recover waste heat up to 525°C at industrial scale. No channeling effect and moderate radial thermal gradient were detected, even though the tank had a horizontal geometry. The plug and play TES presents a non-negligible part of its energy stored in the insulant, which can be recovered during discharge. To take into account such phenomenon, a one-dimension 3 temperature model is proposed. The model fitted well with experimental results, with a root mean standard deviation of the model below 20°C for the temperature profiles.

1026 Associations Between Physiological Arousal and Executive Function in Adults With Chronic Widespread Pain and Insomnia Complaints

Abstract Introduction Individuals with chronic widespread pain (CWP) commonly experience increased physiological arousal, insomnia symptoms, and cognitive disturbance. Higher arousal (as measured by heart rate variability, HRV) is associated with worse executive function in healthy adults, suggesting that hyperarousal selectively disrupts prefrontal cortical activity. However, the HRV/cognition relationship in CWP, the moderating impact of insomnia severity, as well as the components of executive function affected, are unclear. The present study assessed independent associations between HRV and components of executive functioning in patients with CWP and insomnia complaints, and evaluated whether these associations depend on insomnia severity. Methods Forty-two adults (Mage=46.2, SD=13.7) with comorbid CWP and insomnia complaints (difficulty falling/staying asleep plus daytime dysfunction) underwent 5-minutes of Holter monitoring to assess resting HRV. The root mean standard deviation of successive normal to normal heartbeats (RMSDNN) was computed as the HRV index. Participants completed the Insomnia Severity Index (ISI). Participants also completed three computerized tasks measuring executive function: Stroop task (inhibition), Sternberg task (working memory), and the Balloon Analogue Risk Task (risk taking behavior). Multiple regressions examined whether RMSDNN independently predicted or interacted with ISI to predict cognition, controlling for age. Results RMSDNN independently predicted Stroop performance, with higher RMSDNN (lower arousal) associated with lower interference scores (better inhibitory function), B=-.003, SE=.001, p=.029, Full Model R2=.31. RMSDNN and ISI did not independently predict or interact to predict Sternberg/BART performance. Conclusion In patients with CWP and insomnia symptoms, reduced physiological arousal was associated with better inhibition, and this did not depend on insomnia severity. Findings highlight the potential underlying role of hyperarousal in a specific component of executive disruption in CWP. Results suggest that treatments aimed at reducing physiological arousal in comorbid CWP and insomnia (e.g., relaxation, HRV biofeedback) may selectively improve inhibitory function. Findings warrant further consideration in larger samples and prospective analyses. Support Research was supported by the National Institute of Nursing Research (NR017168; PI: McCrae). Data collected as part of clinical trial NCT02001077 Sleep and Pain Interventions (SPIN2) at the University of Missouri (PI: McCrae).

Design and Fabrication Challenges of a Highly Sensitive Thermoelectric-Based Hydrogen Gas Sensor.

This paper presents a highly sensitive thermoelectric sensor for catalytic combustible gas detection. The sensor contains two low-stress (+176 MPa) membranes of a combination of stoichiometric and silicon-rich silicon nitride that makes them chemically and thermally stable. The complete fabrication process with details, especially the challenges and their solutions, is discussed elaborately. In addition, a comprehensive evaluation of design criteria and a comparative analysis of different sensor designs are performed with respect to the homogeneity of the temperature field on the membrane, power consumption, and thermal sensitivity. Evaluating the respective tradeoffs, the best design is selected. The selected sensor has a linear thermal characteristic with a sensitivity of 6.54 mV/K. Additionally, the temperature profile on the membrane is quite homogeneous (20% root mean standard deviation), which is important for the stability of the catalytic layer. Most importantly, the sensor with a ligand (p-Phenylenediamine (PDA))-linked platinum nanoparticles catalyst shows exceptionally high response to hydrogen gas, i.e., 752 mV at 2% concentration.

Development of hydroxamic acid derivatives as anticancer agent with the application of 3D-QSAR, docking and molecular dynamics simulations studies

The inhibition of histone deacetylase (HDAC) has become a well-recognized target for cancer therapy. Until now only five HDAC inhibitors i.e., SAHA, romidepsin (FK-228), belinostat, chidamide, and panobinostat have been approved by FDA. The first four of them are being employed for the treatment of cutaneous T-cell lymphoma and last one is being used for the treatment of multiple myeloma. In the present study, structure and ligand-based computational approaches were selected to design novel histone deacetylase inhibitors. A ligand-based pharmacophore model was developed employing phase module that exhibited five similar features and the generated pharmacophore models were validated by enrichment studies using the decoy set. Atom-based 3D-QSAR model was developed and validated using internal, partial least square (PLS) and external validation methods. The best 3D-QSAR model exhibited high value of regression coefficient for training set (R2) = 0.926 and test (R2) = 0.699, cross-validated coefficient (rcv2) = 0.967 and R2 pred = 0.6578 with low root mean standard deviation (RMSE) = 0.4963. Additionally, the selected pharmacophore model (AAADR.12514) was employed as a 3D query for virtual screening against the ZINC database. The hit compounds were subsequently subjected to ligand–receptor interaction studies. Further, HDAC receptor-ligand complex were subjected to MM-GBSA and molecular dynamic simulation to evaluate the binding energy, strain energy, stability, and electrostatics of complex. Moreover, ADMET studies were also performed on resulted molecules. The outcome of these studies could be utilized for identification of novel lead for the development of HDAC inhibitors.

ANALISIS DINAMIKA MOLEKUL PROTEIN LYSOZYME PUTIH TELUR DENGAN MODEL POTENSIAL LENNARD-JONES MENGGUNAKAN APLIKASI GROMACS

The molecular dynamic analysis oflysozyme protein has been done using Gromacs application. Lysozyme protein filled by water in the cubic form with variation of temperature was 300 K, 3 25 K, and 350 K and calculat ed potential energy values used Lennard Jones equation . Structure protein on temperature was 300 K showed that pressure value was 2 , 54 barand density value was 997,54 kg/m 3 then protein change d in unfolded state on ARG21-CA and SER81-CAamino acid chain with potential energy was 2992,14 kJ/mol . Structure protein on temperature was 325 K showed that pressure value was 4,84 barand density value was 974 kg/m 3 then protein change d in unfolded state on ASP101-CA and GLN121-CAamino acid chai nwith potential energy was 2994,55 kJ/mol .Structure protein on temperature was 350 K showed that pressure value was 0,82 barand density value was 94 8,747 kg/m 3 then protein change d in unfolded state on ARG21-CA amino acid chai n and lost on GLN121-CA amino acid chain with potential energy was 2994,55 kJ/m ol. Root Mean Standard Deviation (RMSD) showed that the protein will be denaturate d on temperatur e 350 K caused bylost on GLN121-CA amino acid with distance was 0.07 nm.

Rational Methods to Pharmacologically Target IDPs: Developing Modulators of Tau Aggregation

Despite a large amount of time and effort invested, the development of drugs targeting intrinsically disordered proteins (IDPs) is a major open problem in pharmacology. Classic drug development strategies are impeded by the highly dynamic nature of IDPs. We propose a strategy to identify inhibitors of the pathological aggregation of the IDP tau, implicated in Alzheimer's disease and other neurodegenerative disorders. We approach this problem by utilizing computational approaches and in vitro experiments to develop new modulators of tau aggregation as discussed below.Initially, computational simulations were used to generate conformational ensembles of tau244-372, the aggregation-prone microtubule binding region of tau. For this purpose, conventional molecular dynamics (MD) simulations were compared against enhanced sampling methods, including a recently developed novel approach based on repeated simulated annealing (ReSA).Preferentially sampled conformations within these dynamic ensembles were identified based on local and global structural similarity. To do this, the structures were grouped together based on root mean standard deviations (RMSD) between conformations and representative structures then generated from these groups. Subsequent computational screening identified selective ligands of these preferentially sampled structures by creating receptor force-fields from the representative structures and scoring potential ligand affinity based on steric, electrostatic and hydrophobic properties.Finally, computational hits were validated using a variety of biophysical methods including fibril-formation assays and single-molecule fluorescence approaches such as fluorescence correlation spectroscopy.This strategy has the potential to enhance our ability to rationally target IDPs for pharmacological intervention and may prove valuable in tackling other IDP-related pathologies such as Parkinson's disease, Diabetes, and Huntington's disease.

Virtual Surgical Planning for Orthognathic Surgery Using Digital Data Transfer and an Intraoral Fiducial Marker: The Charlotte Method

We describe an alternative workup protocol for virtual surgical planning of orthognathic surgery using an intraoral fiducial marker, clinical photography, and the digital transfer of occlusal data. Wealso discuss our initial experience using this protocol in a series of patients. A retrospective cohort study was performed of consecutive patients who had undergone combined maxillary and mandibular osteotomies for the correction of dentofacial deformities at 1 center. These patients underwent treatment planning using the modified virtual surgical planning protocol described in the present report. The primary outcome evaluated was the accuracy of the method, which was determined through superimposition of the surgical plan to the postoperative cone-beam computed tomography (CBCT) scan. The secondary outcomes included the accuracy of the natural head position readings and the adequacy of the CBCT scanned stone models for the fabrication of occlusal splints. The population included 25 patients. The root mean standard deviation (RMSD) from the preoperative plan to the postoperative scan at the maxillary cephalometric points was 1.2, 1.4, and 2.1mm in the axial, sagittal, and coronal planes, respectively. The RMSD of the superimposed plan to the postoperative scan at the 3 mandibular cephalometric points was 1.2, 0.8, and 0.7mm in the axial, sagittal, and coronal planes, respectively. The average variance from the axial, sagittal, and coronal planes for the natural head position was 0.05, 2.22, and 0.69 mm, respectively. All splints fabricated from the CBCT occlusal data fit the stone models and were used intraoperatively. In the subset of patients whose models were both digitally transferred and laser scanned, the superimposition of the laser scan data to the CBCT scanned data was found to have a maximum variation of 0.2mm at the occlusal level. The use of an intraoral fiducial marker changed the workflow for the data collection needed for virtual surgical planning of the correction of dentofacial deformities, while still obtaining accurate results. Because the device does not cause lip distortion, the possibility of virtually predicting a more expectant postoperative lip position exists without the need for additional scans. Furthermore, this work flow allows the transfer of data to be isolated to digital media.

Applications of Real-Time Thermoregulatory Models to Occupational Heat Stress

A real-time thermoregulatory model using noninvasive measurements as inputs was developed for predicting physiological responses of individuals working long hours. The purpose of the model is to reduce heat-related injuries and illness by predicting the physiological effects of thermal stress on individuals while working. The model was originally validated mainly by using data from controlled laboratory studies. This study expands the validation of the model with field data from 26 test volunteers, including US Marines, Australian soldiers, and US wildland fire fighters (WLFF). These data encompass a range of environmental conditions (air temperature: 19-30° C; relative humidity: 25-63%) and clothing (i.e., battle dress uniform, chemical-biological protective garment, WLFF protective gear), while performing diverse activities (e.g., marksmanship, marching, extinguishing fires, and digging). The predicted core temperatures (Tc), calculated using environmental, anthropometric, clothing, and heart rate measures collected in the field as model inputs, were compared with subjects' Tc collected with ingested telemetry temperature pills. Root mean standard deviation (RMSD) values, used for goodness of fit comparisons, indicated that overall, the model predictions were in close agreement with the measured values (grand mean of RMSD: 0.15-0.38° C). Although the field data showed more individual variability in the physiological data relative to more controlled laboratory studies, this study showed that the performance of the model was adequate.

Sky luminance distribution in the North of Iberian Peninsula during winter

This work is based on the study of outdoor daylight conditions during the winter period in Pamplona (the Iberian Peninsula). The 15 standard sky types proposed by the Commission Internationale de l’Eclairage (CIE) are used. The selected sky type in each moment is the one exhibiting the lowest root mean standard deviation (RMSD) when the theoretical and experimental luminance distributions in the sky hemisphere are compared. The selection was derived from luminance distribution data from 145 patches of the sky hemisphere and registered every 10 min from October to March from 2007 and 2008. The most frequent sky type observed in winter in Pamplona is V.5 (cloudless polluted with a broad solar corona), with a frequency of occurrence of 21%. Notwithstanding, the group of overcast skies exhibits a slightly higher frequency (40%) than the clear skies (37%). Seven out of the 15 standard sky types, i.e.V.5, I.1, III.4, II.1, IV.4, II.2 and III.3, are practically 80% of those under study. In order to provide a possible application in daylight climates studies, the frequency of occurrence of the 15 sky types is included in eleven intervals of solar elevation on the threshold corresponding to the time period and the location considered.

Vibrational spectra of indene. Part 4. Calibration, assignment, and ideal-gas thermodynamics

The vibrational spectra of indene have been examined in the vapor and the liquid state using infrared and Raman spectroscopy. Wavenumbers of the liquid spectra are measured to 0.1 cm −1 to re-examine the potential of indene as a calibration molecule. An assignment for its normal modes of vibration is made considering vapor band shapes, polarization ratios and calculated frequencies from a scaling procedure of the indene AM1 force field. An AM1 analysis of the cyclopentadiene vibrations is performed to obtain the scale factors for the constituent five-membered ring. The root-mean standard deviation of the calculated relative to the observed frequencies is 11 cm −1 for the planar modes and 16 cm −1 for the nonplanar modes. The potential energy distribution for the nonplanar modes from a refinement calculation is discussed. Ideal-gas thermodynamic functions are evaluated using the vapor phase vibrational wavenumbers and the previously reported moments-of-inertia. The spectroscopic ideal-gas entropy exceeds that determined from calorimetry by ≈ 0.95 R (R = 8.31451 J K −1 mol −1) from 300 to 500 K, indicating that the crystal most probably contains some residual disorder at 0 K.