Miracle-dz/UniFAR-FTUs huggingface dataset:
The Challenge of Considering Receptor Flexibility in Ligand Docking and Virtual Screening

Computational ligand docking and screening is widely employed throughout the pharmaceutical industry to speed up the drug discovery process and identify drug candidates from very large pools of virtual compound libraries. When a ligand interacts with a receptor a number of structural changes within the ligand binding site might occur. It is therefore critical for these methods to accurately predict, or otherwise take into account the receptor flexibility upon ligand binding. This flexibility within the binding pocket explains why a diverse range of ligand sizes and shapes can sometimes bind to the same receptor pocket. This observation supersedes the notion that ligand-receptor interaction is a purely lock and key mechanism. The capability to correctly predict molecular interactions is critical for computer-aided molecular design technology. In this review, we discuss biological cases of receptor flexibility upon ligand binding that can range from large-scale movement of loops to single gate-keeper amino acid movements. In addition, we provide further evidence that rigid receptor docking alone will more than likely fail in the drug-discovery process. We then discuss computational methods, which have been developed to mimic flexibility within the binding pocket and predict ligand-receptor interactions. Early flexible receptor docking methods used soft-potential docking and rotamer libraries. More recently methods have focused on constructing an ensemble of structures generated by a variety of means including X-ray crystallography, NMR, Monte Carlo sampling, Normal Modes-based methods and Molecular Dynamics. It is evident that methods that ignore receptor flexibility can result in poorly docked solutions and therefore the challenge is to develop computational methods, which can accurately and efficiently predict this phenomenon.
Targeting Metabolic Survival Pathways in Lung Cancer via Combination Therapy

Abstract : This proposal aims to identify critical metabolic pathways necessary for survival of liver kinase B1 (LKB1)-deficient non-small cell lung cancer (NSCLC) cell lines. We have conducted 13C metabolic flux analysis studies in LKB1 proficient or deficient NSCLC cells under nutrient complete or metabolic stress conditions (e.g. hypoxia, matrix detachment). Using these analyses we can demonstrate that cells lacking the LKB1 tumor suppressor exhibit limited oxidation of glucose-derived pyruvate in mitochondria. LKB1-deficient cells also exhibit increased reliance on glutamine metabolism. Treatment with biguanides such as metformin or phenformin decreases oxidative mitochondrial metabolism. A critical defect we have observed in our analyses is the inability of LKB1- deficient tumor cells to recover in response to phenformin treatment, as carbohydrate oxidation remains compromised for an extended period of time after removal/washout of phenformin. Given the dependence of LKB1-deficient tumor cells on glutamine metabolism, we are targeting a critical enzyme responsible for catalyzing the entry of glutamine carbon into the Krebs cycle in mitochondria, glutaminase.
Foraging Behavior of Northern Bobwhites in Relation to Resource Availability

Distribution of food resources may influence northern bobwhite (Colinus virginianus) foraging decisions and demographic rates. We tested whether covey movements were sensitive to food availability by spreading sorghum (Sorghum bicolor) every 15 days at 3 rates; high rate (174 L/ha/yr), low rate (44 L/ha/yr), and no feed on 3 sections (~240 ha each) of Tall Timbers Research Station, 2009–2010. We measured sorghum availability spread along a 17 km feeding trail every 5 days. We determined seasonal (1 Nov 15 Mar) home ranges of radio-tagged coveys (n1⁄4 89) and daily movement rates and home ranges of a subset of coveys located every 30 mins, sunrise to sunset (1 Feb 15 Mar). Diet was determined from harvested bobwhites. Mean sorghum availability (seeds/0.5m) on the feed trail declined from 50 seeds at day 1 to 12 seeds at day 15, and 11 seeds at day 1 to 0 seeds at day 10, for high and low rates, respectively. Seasonal home ranges did not differ among treatments; however, daily home ranges were smaller for coveys on the high rate areas, as was dispersion of locations within home ranges. Distances to the feed trail from covey and random locations were similar. There was no difference in distance traveled (25.20 m; SE1⁄4 0.65) between consecutive covey locations among treatments. Proportion of sorghum in the diet declined precipitously when ,15 seeds/0.5m. We estimated an empirical giving up density of 10–14 seeds/0.5m, ~1.6 kcals/ 0.5m. Food availability, even at high levels, marginally affected covey space use and movement rates during late winter. Other factors affecting bobwhites, such as predator avoidance, or thermal regulation, may have a more significant effect on bobwhite covey daily movements and space use. Citation: Miller, R. S. , W. E. Palmer, S. D. Wellendorf, and L. W. Burger, Jr. 2017. Foraging behavior of northern bobwhites in relation to resource availability. National Quail Symposium Proceedings 8:207–214.
Sub-pixel image registration with a maximum likelihood estimator. Application to the first adaptive optics observations of Arp 220 in the L' band

We present a new method based on a maximum likelihood (ML) estimation of the sub-pixel shift between images of a given object observed with a single instrument. We first study the case of two noisy images and give the ML approach of the registration problem. By means of simulations, we show the gain obtained with this ML solution compared to a classical registration method with an academic noise model (stationary white Gaussian), and then demonstrate the relevance of this ML estimation with a more realistic noise model. We then address the problem of a sequence of low signal frames of the same object. We develop a joint ML approach in which we simultaneously estimate the reference (i.e. the noiseless) image and the shift parameters. The registration accuracy is increased at low photon levels as the number of frames grows, reaching the sub-pixel domain at very low SNR (about 1), when considering 100 frames. When applied to experimental data (thermal IR images of a faint galaxy), both ML methods show their efficiency to recover the resolution in averaged frames and totally outperform the classical cross-correlation.
Impact of heat and drought stresses on size and quality of the potato yield

Rykaczewska K. (2017): Impact of heat and drought stresses on size and quality of the potato yield. Plant Soil Environ. , 63: 40–46. Potato (Solanum tuberosum L.) is a plant typical mainly for temperate climate and develops best at about 20°C. Heat stress due to increased temperatures is an agricultural problem in many areas in the world. The aim of our work was to assess the response of selected new potato cultivars to heat and drought stress during the subsequent stages of plant growth starting from buds forming. The pot experiment was carried out over the course of two years with the following early cultivars: Lord, Miłek, Gwiazda, Hubal, Oberon and Tetyda. The impact of heat (38°C/25°C) and drought stress on potato plants was tested in four periods of two weeks. In these periods half of the plants were watered to a level close to optimal while the other half remained without irrigation. Our studies demonstrated that tested potato cultivars’ response to heat stress depends on the growth stage, in which the temperature acts on the plants and on the soil moisture. Besides the decrease in yield and tubers’ diminution, the biggest problem was the presence of tubers with physiological defects, particularly of immature tubers. The response of cultivars was differentiated.
Report on volcanic plume measurements on volcanoes in Papua New Guinea

This report summarizes the findings of plume gas measurements conducted on volcanoes of Papua New Guinea (PNG) during September 2016, as part of the DECADE project. The total sulfur dioxide (SO2) and carbon dioxide (CO2) gas fluxes of Tavurvur, Bagana and Ulawun volcanoes were determined by combining groundremote sensing and ground-/airborne direct sampling, depending on the particular conditions on each volcano. During the campaign Tavurvur was degassing passively, without forming a continuous plume, and it was accessible for direct sampling in the crater. Its SO2 emission was found to be 0.19 ± 0.05 kg/s from scanning-DOAS and a stationary wide-field-of-view (WFOV) DOAS monitor, and the fraction of CO2/SO2 molar ratios was 2.6, obtained with a compact multi-GAS instrument. Bagana, on the other hand, had permanent degassing, producing occasional explosions and ash emission. The plume was measured by ground-based scanning-DOAS and a compact multiGAS instrument aboard a multi-rotor UAV, resulting in a SO2 flux of 13 ± 5 kg/s and a CO2/SO2 of 15. Ulawun presented continuous passive degassing, forming an elevated plume which flux and composition were measured by car-traverses with a mobile-DOAS, a stationary dual-beam scanning DOAS, and a multi-GAS/UAV sensor. The SO2 flux of Ulawun was 11 ± 2 kg/s and the CO2/SO2 equal to 4.8. A stationary WFOV-DOAS instrument was left with the Rabaul Volcano Observatory (RVO) for longer-term monitoring of the SO2 flux from Tavurvur.
Regression and analytical models for estimating mangrove wetland biomass in South China using Radarsat images

Mangrove wetlands have been rapidly diminishing because of human pressures worldwide. The Guangdong Province in South China, which has the largest area of mangrove wetlands in the nation, is under severe threat as a result of rapid urbanization and economic development. In this paper, comparisons were made between optical Landsat TM images and Radarsat fine‐mode images for estimating wetland biomass. Regression and analytical models were used to establish the relationships between remote sensing data and wetland biomass. The optimal parameter values for the analytical model were determined using genetic algorithms. Experiments indicate that the models using Radarsat fine‐mode images have significant accuracy improvement in terms of Root Mean‐Square Error (RMSE) whereas the use of the single Normalized Difference Vegetation Index (NDVI) may produce serious errors in biomass estimation. The Radarsat images can obtain more accurate trunk information about mangrove forests because of higher resolution and side‐looking geometry. The use of genetic algorithms can help to decompose backscatter into vegetation and soil backscattering, which is very useful for ecological modelling.
Muscle Proteomics of the Indian Major Carp Catla (Catla catla, Hamilton)

Background: Skeletal muscle proteomics aims at global identification, cataloging and biochemical characterization of the entire protein complement of voluntary contractile tissues. In the lower vertebrates like fish, skeletal muscle contributes 34-48% of the total body weight and the muscle composition contributes strongly to the quality. Characterization of the muscle proteome is a key to many aspects of aquaculture, encompassing physiology, growth, food safety, seafood authentication and quality, traceability and shelf-life. Catla catla is a commercially important carp species contributing a major share to be freshwater aquaculture production in the Indian subcontinent; however, little omics information is available on this species. Methods: In the present study, protein spots excised from 2-D gels of catla muscle proteome were identified through MALDI-TOF-MS. Based on the muscle proteomic information, transcript information on the identified proteins was generated. Results: A reference muscle proteome map for Catla catla was generated and 70 protein spots from 2-D gels, representing 22 proteins, have been identified by MALDI-TOF MS. We have also generated the partial gene sequence information on the identified proteins which have been submitted at GenBank. Conclusion: This is the first study on the muscle proteogenomics of the commercially important carp Catla catla. Besides adding to the existing knowledgebase on comparative muscle proteomics, the information generated would also serve as the baseline proteogenomic information on this Indian major carp.
Estimation of Censored Quantile Regression for Panel Data With Fixed Effects

This article investigates estimation of censored quantile regression (QR) models with fixed effects. Standard available methods are not appropriate for estimation of a censored QR model with a large number of parameters or with covariates correlated with unobserved individual heterogeneity. Motivated by these limitations, the article proposes estimators that are obtained by applying fixed effects QR to subsets of observations selected either parametrically or nonparametrically. We derive the limiting distribution of the new estimators under joint limits, and conduct Monte Carlo simulations to assess their small sample performance. An empirical application of the method to study the impact of the 1964 Civil Rights Act on the black–white earnings gap is considered. Supplementary materials for this article are available online.
Medication Safety in Hospitals: Avoiding Medication Errors in the Medication Use Process

Medication errors have a large impact on patient safety and on healthcare costs. Although errors happen at every stage of the medication use process, the ones that occur in the latter part of the process are frequently undetected. Therefore, while all medication errors need to be eliminated, the ones that frequently reach the patient should be stopped first. Errors occur due to a combination of human and system-related failures. However, improving the system seems to be the prudent approach to avoiding medication errors, as human failures are inevitable. Efforts to improve systems include two broad areas. One is the automation of systems and the other is to improve the quality of prescription writing. Technologies have improved the safety of the medication use process to a large extent but this success depends on user acceptance. If technologies are difficult to use, users may work around standard procedures resulting in new and unanticipated errors. Bar-code assisted medication administration is one such useful technology which is commonly associated with implementation problems and workarounds. Therefore adequate preplanning, user attitude assessments and post-implementation assessments are three vital aspects of implementing new technology. Improving the quality of prescriptions is also a very useful strategy to improve medication safety, because a large percentage of hospitals still use hand-written prescriptions. The use of error-prone abbreviations has been shown to be very dangerous as pharmacists and nurses may misinterprit them, especially if the prescriptions are illegible. A popular approach to discourage error-prone abbreviations in prescriptions is through a ‘Do Not Use’ list; a list showing error-prone abbreviations that should be avoided by prescribers. However, its effectiveness and adherence by healthcare professionals has not been established. In conclusion, medication errors have a large impact on patient safety and interventions aimed at minimising them need careful planning and implementation.
Lepton models for TeV emission from SNR RX J1713.7-3946

Aims. SNR RX J1713.7-3946 is perhaps one of the best observed shell-type supernova remnants with emissions dominated by energetic particles accelerated near the shock front. The nature of the TeV emission, however, is an issue still open to investigation. Methods. We carried out a systematic study of four lepton models for the TeV emission with the Markov chain Monte Carlo method. Results. It is shown that current data already give good constraints on the model parameters. Two commonly used parametric models do not appear to fit the observed radio, X-ray, and γ-ray spectra. Models motivated by diffusive shock acceleration and by stochastic acceleration by compressive waves in the shock downstream give comparably good fits. The former has a sharper spectral cutoff in the hard X-ray band than the latter. Future observations with the HXMT and NuSTAR may distinguish these two models.
Effect of Upper-Ocean Evolution on Projected Trends in Tropical Cyclone Activity

AbstractRecent work has highlighted the possible importance of changing upper-ocean thermal and density stratification on observed and projected changes in tropical cyclone activity. Here seven CMIP phase 5 (CMIP5)-generation climate model simulations are downscaled under IPCC representative concentration pathway 8.5 using a coupled atmosphere–ocean tropical cyclone model, generating 100 events per year in the western North Pacific from 2006 to 2100. A control downscaling in which the upper-ocean thermal structure is fixed at its monthly values in the year 2006 is compared to one in which the upper ocean is allowed to evolve, as derived from the CMIP5 models. As found in earlier work, the thermal stratification generally increases as the climate warms, leading to increased ocean mixing–induced negative feedback on tropical cyclone intensity. While trends in the frequency of storms are unaffected, the increasing stratification of the upper ocean leads to a 13% reduction in the increase of tropical cyclone .
PREVALENCE AND CLINICAL CORRELATES OF PERIPHERAL ARTERIAL DISEASE IN HEMODIALYSIS PATIENTS

Background: Peripheral arterial disease (PAD) is the most common manifestation of systemic atherosclerosis and accounts for significant morbidity and mortality among end-stage renal disease (ESRD) patients. However, few studies have identified the prevalence and clinical correlates of PAD in this specific population. Methods: Two hundred and thirty-four patients receiving stable HD ＞ 3 months from a single center were screened for PAD using the ankle-brachial index (ABI). The ABI was measured and a ratio of ＜ 0.9 was considered abnormal. Several biochemical and inflammatory parameters were also examined. Results: The prevalence rate of PAD (ABI＜0.9) was 27.8%. ABI was positively correlated with serum albumin (r=0.134, p=0.41) and serum HDL-cholesterol (r=0.168, p=0.012) and negatively correlated with age (r=0.135, P=0.039), log-transformed CRP levels (r=-0.173, p=0.008), fasting blood sugar (r=0.263, p＜0.001) and serum triglyceride (r = 0.152, p = 0.20). In univariate analysis, PAD was found to be associated with hypertriglyceridemia, CRP levels, female gender, pre-existing CVD, and diabetes mellitus. Multivariate logistic regression analysis, however, revealed that PAD was associated with diabetes mellitus, pre-existing CVD, duration on dialysis and CRP levels. Conclusion: In this preliminary study, we found that the prevalence of PAD in Taiwanese patients on HD is high. Presence of diabetes, pre-existing CVD, duration on dialysis and CRP levels independently predicts the presence of PAD.
COUPLED OSCILLATOR MODEL OF SPEECH RHYTHM

Attempts to verify instrumentally tendencies toward stress timing or syllable timing have been less than successful, leading many researchers to abandon the rhythm dichotomy as too simplistic. One empirical finding which suggests an underlying unity in the rhythms of different languages is a statistical tendency for duration of stress group to be a linear function of the number of syllables contained in it, with languages differing mainly in the constant term of the linear function. We use a robust mathematical model of simple coupled oscillators to argue that the linear relation observed may reflect a very general tendency of rhythmic systems organized in hierarchical interaction, regardless of concrete details, which may differ in complex ways. In addition, the oscillator model provides a rich conceptual tool for elucidating rhythmical differences in speech behavior.
Do remittances alleviate poverty and income inequality in poor countries? Empirical evidence from sub-Saharan Africa

An attempt has been made in this paper to examine the impact of international remittances on poverty and income inequality in sub-Saharan Africa (SSA). In carrying out the study, 34 SSA countries for which relevant data are available, between 1980 and 2009, were sampled for the poverty analysis whilst a sample size of 36 was used in the remittances-income inequality exploration. A set of dynamic panel-data models was estimated using system Generalized Method of Moments. It was found that remittances have significant poverty-alleviating effect, with the poorest of the poor being the least beneficiaries. Additionally, International remittances have income equalisation effects in countries with relatively narrower income gap, but with an intensifying income-inequality aggravating effects in countries with relatively wider income gap. It is, thus, concluded that although remittances have huge potentials to alleviate poverty and equilibrate incomes in SSA, these remittances have size-effects to the detriment of relatively poorer countries and countries with relatively higher income gap. Therefore, the paper recommends that, although the poverty-alleviating effects and income equalisation effects of remittances cannot be downplayed, it is imprudent for SSA policymakers to overly exclusively on remittances as a poverty-reduction strategy towards sustainable socioeconomic development of the sub-region.
Equilibrium and Kinetic Aspects in the Sensitization of Monolayer Transparent TiO2 Thin Films with Porphyrin Dyes for DSSC Applications

Free base, Cu(II) and Zn(II) complexes of the 2,7,12,17-tetrapropionic acid of 3,8,13,18-tetramethyl-21H,23H porphyrin (CPI) in solution and bounded to transparent monolayer TiO2 nanoparticle films were studied to determine their adsorption on TiO2 surface, to measure the adsorption kinetics and isotherms, and to use the results obtained to optimize the preparation of DSSC photovoltaic cells. Adsorption studies were carried out on monolayer transparent TiO2 films of a known thickness. Langmuir and Frendlich adsorption constants of CPI-dyes on TiO2 monolayer surface have been calculated as a function of the equilibrium concentrations in the solutions. The amount of these adsorbed dyes showed the accordance with Langmuir isotherm. Kinetic data on the adsorption of dyes showed significantly better fits to pseudo-first-order model and the evaluated rate constants linearly increased with the grow of initial dye concentrations. The stoichiometry of the adsorption of CPI-dyes into TiO2 and the influence of presence of coadsorbent (chenodeoxycholic acid) have been established. The DSSC obtained in the similar conditions showed that the best efficiency can be obtained in the absence of coadsorbent with short and established immersion times.
Institutional Development of Irrigation Management Based on the Local Wisdom in Indonesia

During 1980-1997, the management of water resources was done with a supply-driven approach. This approach results in the expensive maintenance of water resources and the disregarded resources utilization of environmental sustainability. Since 1998, The Government of Indonesia began to reform institutional irrigation with the financing supported by the World Bank. However, the institutional reforms of the irrigation have not yet reflected the exact changes as expected. Therefore, it is necessary to study the process of strengthening the institutional management of irrigation based on the local wisdom through the inventory of history series of irrigation management policy and empowerment of capacity building and institutional program of irrigation management. This paper presents an effort to develop the institutional irrigation management by exploring the local wisdom in the community. It can be used as a guide for future sustainable management of irrigation.
Sustainable practices in small and medium sized enterprises in regional Australia

ii Statement of Authorship . iv Acknowledgments . v Dedication . vi Publications and Proceedings Arising from this Thesis . vii List of Tables . xiv Abbreviations . xviii Chapter 1: Introduction . 1 1.