Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Oxidation Sites for Low Redox Potential Substrates

Background: Versatile peroxidases oxidize different substrates, including low redox potential aromatics. Results: To investigate this activity, 13 variants were characterized, and five x-ray structures obtained. Conclusion: Phenols and dyes are oxidized in a low efficiency site in the heme channel and a high efficiency site at an exposed tryptophan. Significance: This study supplies new structural-functional information on versatile peroxidase, and provides variants with improved activity on phenols. Versatile peroxidase shares with manganese peroxidase and lignin peroxidase the ability to oxidize Mn2+ and high redox potential aromatic compounds, respectively. Moreover, it is also able to oxidize phenols (and low redox potential dyes) at two catalytic sites, as shown by biphasic kinetics. A high efficiency site (with 2,6-dimethoxyphenol and p-hydroquinone catalytic efficiencies of ∼70 and ∼700 s−1 mm−1, respectively) was localized at the same exposed Trp-164 responsible for high redox potential substrate oxidation (as shown by activity loss in the W164S variant). The second site, characterized by low catalytic efficiency (∼3 and ∼50 s−1 mm−1 for 2,6-dimethoxyphenol and p-hydroquinone, respectively) was localized at the main heme access channel. Steady-state and transient-state kinetics for oxidation of phenols and dyes at the latter site were improved when side chains of residues forming the heme channel edge were removed in single and multiple variants. Among them, the E140G/K176G, E140G/P141G/K176G, and E140G/W164S/K176G variants attained catalytic efficiencies for oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) at the heme channel similar to those of the exposed tryptophan site. The heme channel enlargement shown by x-ray diffraction of the E140G, P141G, K176G, and E140G/K176G variants would allow a better substrate accommodation near the heme, as revealed by the up to 26-fold lower Km values (compared with native VP). The resulting interactions were shown by the x-ray structure of the E140G-guaiacol complex, which includes two H-bonds of the substrate with Arg-43 and Pro-139 in the distal heme pocket (at the end of the heme channel) and several hydrophobic interactions with other residues and the heme cofactor.
Ventilatory function in healthy adult Nigerians.

SUMMARY 1. Static and dynamic lung volumes (yC, FEV lo FRC, ERV, RV and TLC) have been determined in 291 adult healthy Nigerians (174 males and 117 females). 2. Prediction formulae of various authors on Caucasians and South African Bantu have been applied to the Nigerian data. The results show significantly smaller VC, FEV 1 , FRC, RV, TLC and RV/TLC in Nigerians than in Caucasians. The VC, FEV 1 and FRC of Nigerians were similar to those of South African Bantu. 3. ERV values were similar to those previously reported by other authors for Caucasians. The combination of lower RV values and similar ERV indicates the possibility of less 'basal airway closure' in Nigerians. Several investigators have shown the lung volumes of Africans and peoples of African descent to be significantly less than the values for Caucasians when standardized for age and height (Smillie & Augustine, 1926; Roberts & Crabtree, 1927; Gilson, Stott, Hopwood, Roach, McKerrow & Schilling, 1962; Abramowitz, Leiner, Lewis & Small, 1965; Johannsen & Erasmus, 1968; Hearn, 1968; Oduntan, 1970). Other racial groups also shown to have lower lung volumes compared with Caucasians include Chinese (Foster, 1924), Indians (Rao, Gupta Sen, Saha & Devi Sita, 1961; Cotes & Malhotra, 1965; Bhattacharya & Banerjee, 1966) and Maoris (Glass, 1962). These findings support the need for each racial or ethnic group to have its own 'normal' standards of pulmonary function. The aim of the present study was to establish 'normal' values for ventilatory functions in Nigerians. A sample of 291 healthy Nigerian adults were studied. All the sub-divisions of total lung capacity were compared with values predicted by formulae previously derived by other authors for Caucasians and for South African Bantu. Whereas the lung volumes of Nigerians are very similar to those ofSouth African Bantu, the present study confirms the differences previously reported by other workers between the lung • This paper forms part of a thesis approved by the University of Aberdeen, Scotland, for the M.D. degree. Correspondence: Dr D. Femi-Pearse, Cardiothoracic Research Laboratory, Lagos University Teaching Hospital, Private Mail Bag 12003, Lagos, Nigeria.
Structure of products prepared by freeze-drying solutions containing organic solvents.

An increasing number of parenteral products are being prepared by freeze-drying techniques. In this method, a sterile aqueous solution of the drug is frozen in a sterile container and the ice and bound water are removed aseptically by sublimation and vacuum drying, respectively. The method reduces the particulate contamination and improves the product quality. The purity of the product may be increased and the dissolution rate on reconstitution is enhanced. Solutions of pharmaceutical powders, prepared for freeze-drying often contain various concentrations of organic solvent. The solvents may be added to reduce the degradation rate of the active material in water during processing or may be present as a residual impurity in the pharmaceutical powder or bulk intermediate used to prepare the freeze-drying solution. The presence of organic solvents affects the freezing characteristics of products cooled by conventional techniques. The solvents may freeze or remain present as an unfrozen liquid residue distributed throughout the ice matrix as an interconnecting capillary network. The solvents retain varying quantities of associated water and various concentrations of dissolved drug. The volumes vary and are related to the hydrophilic properties of the solvent. The presence of solvents affects the rate of drying and influences the choice of plant design, the production capacity, and the product quality. Products which are frozen, dry rapidly by direct sublimation drying. In semi-frozen systems, the products dry more slowly by the simultaneous sublimation of ice and the evaporation of the liquid solvents. In this paper, the freeze-drying properties of a number of drug solutions containing various organic solvents have been studied. Several drugs have been processed from aqueous solution containing up to 20% of ethanol, n. propanol, n. and tert. butanol, ethylacetate, dimethyl carbonate, acetonitrite, dichloromethane, methylethyl ketone, and methylisobutyl ketone. The studies have been conducted in a small research dryer and in both pilot plant and large scale industrial freeze dryers. In this paper, the principles of the methods are reviewed and the physical chemistry of the operation is discussed. The mechanisms of freeze-drying are elucidated and the characteristics of the finished products are compared.
Surrogate endpoints: wishful thinking or reality?

Generally, before a new drug can be accepted for the use in clinical practice, its efficacy and safety needs to be rigorously assessed in a series of clinical trials. This process of testing a new therapy can (and, in fact, does) take many years. One of the reasons is the use of long-term clinical endpoints like clinical progression or survival. However, recent advances in the understanding of the biological mechanisms of disease development have resulted in the emergence of a large number of potentially effective new agents. There is also increasing public pressure for promising new drugs to receive marketing approval as rapidly as possible, in particular for life threatening diseases such as cancer. For these reasons, there is an urgent need to find ways of shortening the duration of cancer clinical trials. A possible solution to this problem is to replace the endpoint of interest, the ‘true’ endpoint, by another one, a ‘surrogate’ endpoint, which might be measured earlier or more frequently. However, before a surrogate can replace a true endpoint, it should be validated. This means that it should be checked whether the use of the surrogate leads to correct conclusions about the effect of the treatment on the true endpoint. The validation of a candidate surrogate endpoint is not straightforward. Merely establishing a correlation between both endpoints is not sufficient.1 Formal methods, allowing for validation of surrogate endpoints, have become the subject of intensive research over the past decades.2 Until recently, the statistical approaches developed for this purpose were based on the definition of a surrogate proposed by Prentice,3 according to which a surrogate endpoint is ‘a response variable for which a test of the null hypothesis of no relationship to the treatment groups under comparison is also a valid test of the corresponding null hypothesis based on the true endpoint. ’ The methods assumed the availability of data from a single trial.3–5 These methods suffer from numerous drawbacks: some of them are too stringent to be of practical value, while others are based on non-testable assumptions.6 To overcome these limitations, ‘meta-analytic’ validation approaches have recently been developed.7–10 They are based on an alternate definition, according to which ‘a surrogate endpoint is expected to predict clinical benefit (or harm or lack of benefit or harm)’. 11 These methods use large databases from multiple randomized clinical trials and aim at measuring directly the association between the treatment effects on the surrogate and the true endpoint. At the 33rd International Biometric Conference, which took place on 16–21 July, 2006, in Montreal, a special Topic Contributed Session ‘Surrogate Endpoints: Wishful Thinking or Reality? ’ was devoted to the issue of surrogate endpoint validation. Each speaker was provided with two datasets, containing data from multiple randomized clinical trials in colorectal cancer. The speakers were asked to evaluate, using different
ICT AND SOCIO-ECONOMIC TRANSFORMATION: THE EXPERIENCE OF NIGERIA

The emergence of information and communication technology (ICT), especially in developing countries, can best be described as epochal. This is mainly because of the socio-economic transformation it has brought about. Virtually every aspect of modern life has been touched by ICT: countries have witnessed massive injection of funds through direct foreign investment, banking operations have been revolutionised, hitherto unknown employment creation opportunities have become a reality, business operations have been enhanced without the necessity for physical contact, and vehicular movement has been enhanced in many countries. In many developing countries, the traditional drawbacks of poor infrastructure have been largely overcome through the deployment of ICT. In many African countries, however, the actual impact of ICT on socio-economic development has yet to be studied in any systematic way – a lapse attributable in part to the fast pace of change that characterises the ICT sector, but also to the fact that compared to the developed countries, African countries still lag behind in ICT investment, and the low-level of support by government and the private sector to research devoted to track development trends. This paper explores current literature on the impact of ICT on socio-economic transformation based on the Technology Acceptance Model (TAM) of Fred D Davis (1989). Focusing on Nigeria, but with lessons drawn from South Africa and other African countries, the paper highlights, among other things, the factors that enhance or inhibit the contributions that ICT could make in the country’s drive to transform the economy.
User‐centric versus network‐centric load balancing: How to provide good QoE for gold users

The predicted increase in mobile data traffic and in the number of mobile users poses challenges for network operators. Future mobile networks should support traffic volumes of several orders of magnitude larger than today. This may create situations in which the transmission capacity of the network is inadequate for the traffic demand. Intelligent and robust network management methods are thus needed to handle the upcoming changes. Because quite often the bottleneck lies in the wireless part of the network, it is essential to have methods in place to select appropriate wireless access points for the users or their applications. This can be performed either by a central entity or in a distributed manner in which the intelligence is placed in the user equipment or hybrid combinations of those. The selection criteria may vary from selfish optimization of a single user's quality of experience to global network load balancing and class‐wise prioritization. This work explores the wireless access selection scheme from a system perspective in scenarios where users of different subscription classes are using progressive video streaming. Evaluation is carried out between a Q‐learning based user‐centric algorithm, a user class aware network‐centric algorithm and a setting without handovers. Simulation results show that both user‐centric and network‐centric algorithms are able to improve the network performance and the quality of experience of the users. The gains of the network‐centric algorithm are more evident during high congestion. In a lightly congested network, the distributed selfish optimization is also qualitatively a good solution for gold users. Copyright © 2015 John Wiley & Sons, Ltd.
Capability in Reading By Using Indonesian as The National Language for Male Children at the Fifth Grade Students of Elementary School: Psycholinguistic Approach

The aim of this research was to investigate whether the male children could use Indonesian in reading well as the national language. This research could show the phenomena of language development in using national language. We conducted a qualitative study. We recorded 5 male students. We were recording them while they were reading the book which the title was ‘frog, where are you? ’ by Mercer Mayer. This book only consisted of pictures without any texts. We focused on the students’ ability in producing simplex and complex clauses. The findings showed that the students were good at reading because the finding showed that four students from five students chose to use complex sentences
PEAT, how much am i burning?

Depletion of fossil fuel and the ever-increasing need for energy in residential and commercial buildings have triggered in-depth research on many energy saving and energy monitoring mechanisms. Currently, users are only aware of their overall energy consumption and its cost in a shared space. Due to the lack of information on individual energy consumption, users are not being able to fine-tune their energy usage. Further, even-splitting of energy cost in shared spaces does not help in creating awareness. With the advent of the Internet of Things (IoT) and wearable devices, apportioning of the total energy consumption of a household to individual occupants can be achieved to create awareness and consequently promoting sustainable energy usage. However, providing personalized energy consumption information in real-time is a challenging task due to the need for collection of fine-grained information at various levels. Particularly, identifying the user(s) utilizing an appliance in a shared space is a hard problem. The reason being, there are no comprehensive means of collecting accurate personalized energy consumption information. In this paper we present the Personalized Energy Apportioning Toolkit (PEAT) to accurately apportion total energy consumption to individual occupants in shared spaces. Apart from performing energy disaggregation, PEAT combines data from IoT devices such as smartphones and smartwatches of occupants to obtain fine-grained information, such as their location and activities. PEAT estimates energy footprint of individuals by modeling the association between the appliances and occupants in the household. We propose several accuracy metrics to study the performance of our toolkit. PEAT was exhaustively evaluated and validated in two multi-occupant households. PEAT achieves 90% energy apportioning accuracy using only the location information of the occupants. Furthermore, the energy apportioning accuracy is around 95% when both location and activity information is available.
Causal Inference and Prediction in Health Studies: Environmental Exposures and Schistosomiasis, HIV-1 Genotypic Susceptibility Scores and Virologic Suppression, and Risk of Hospital Readmission for Heart Failure Patients

Causal inference-inspired semi-parametric methods of measuring variable importance are well designed to answer questions of interest in health settings. Unlike traditional regression approaches, such variable importance measures are based on causal parameters that have straightforward real-world definitions, regardless of the approach used to estimate them. Parameters of regression models, in contrast, are not at all straightforward to interpret in real-world settings, because their definition relies completely on the correctness of the pre-specified model. Prediction-focused machine learning methods can avoid the issues of model pre-specification, but still do not provide estimates of variable importance that can be easily interpreted; the set of predictors chosen can also be highly variable. Semi-parametric methods combine the best of both approaches, and are able to utilize data-adaptive estimation algorithms while still returning a parameter estimate that is meaningful and can be simply understood. In this dissertation, semi-parametric methods to assess variable importance are applied to three real-world health applications: the relationship between types of water contact and the prevalence of schistosomiasis infection in rural China; HIV-1 treatment regimen genotype susceptibility scores and their relationship with the rate of virologic suppression; and the impact of a telemanagement program on and the association of multiple risk factors with the rates of hospital readmission for heart failure patients. Emphasized are (1) the choice of parameter of interest as motivated by the research question, (2) estimator choice based on a consideration of theoretical properties and performance under non-ideal conditions, and (3) the use during the estimation process of machine learning algorithms and algorithms that utilize multiple candidate models. Four different causal parameters are defined and described, and multiple estimators are considered. Each data analysis presents different opportunities to investigate aspects of causal inference-based semi-parametric methods. In the schistosomiasis analysis, a traditional regression approach is compared with semi-parametric methods. Estimator performance is compared in the HIV analysis, particularly in the context of the observed extreme violations of the experimental treatment assignment (ETA) assumption. The G-computation estimator, the inverse-probability-of-censoring-weighted (IPCW), its double-robust counterpart (DR-IPCW), and the targeted maximum likelihood estimator (TMLE), are included in this comparison. The heart failure analysis addresses differences in causal parameter definition for a community-level treatment, and the related assumptions that must be added to the typical theoretical framework. Also included in this analysis is a comparison of super learning with traditional regression in terms of predictive performance.
An Approach for Hierarchical RBAC Reconfiguration With Minimal Perturbation

In recent years, role-based access control (RBAC) has become the de facto access control model due to its good applicability and high flexibility. Since the organizations need to update the access control policies to meet the changes in employees, departments, business processes, and so on. The RBAC system has to define new roles and becomes more and more bloated because it’s difficult to modify the role-permission assignment with no or minimal impact to other users and roles. Hence, there is a great need to reconfigure the RBAC system over time to reduce its structural complexity and keep as close as possible to the original. Several RBAC reconfiguration approaches have been proposed aiming at generating roles similar to the deployed ones, but they neglect the differences in deployed roles that some of them are useless for the system and generate more roles than needed, which in turn increases the system structure complexity. In this paper, we first propose three indicators to evaluate the quality of deployed roles and define the problem of hierarchy RBAC reconfiguration with minimal weight structure complexity and perturbation. Then, the hierarchy RBAC reconfiguration approach and its algorithm process are proposed to address the problem. To conclude, we demonstrate the effectiveness and stability of our approach through experiments.
Normalization by gluing for free λ-theories

The connection between normalization by evaluation, logical predicates and semantic gluing constructions is a matter of folklore, worked out in varying degrees within the literature. In this note, we present an elementary version of the gluing technique which corresponds closely with both semantic normalization proofs and the syntactic normalization by evaluation We will expand in more detail the insight presented in Streicher’s short note [Streicher, 1998] and in Fiore [2002], giving some explicit constructions. We will be considering the case of free λ-theories generated from many-typed first-order signatures. 1 λ-signatures and λ-theories Definition 1.1 (Arity). A simply-typed first-order arity for a set T of atomic types is a pair α ≡ (? ⃗? , τ) of a list of types and a types. We write T† ≝ T⋆ × T for the set of such arities. Definition 1.2 (Many-typed signature). Following Jacobs [1999], a many-typed signature Σ ≡ (U, ∂) is a set of atomic typesU together with an arity-indexed family of sets of operations ∂, taking each operation θ to ∂(θ) ∈ U†. More abstractly, the category Sig of such signatures arises as the pullback of the fundamental fibration along the arity endofunctor.