Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitory Potency of 8-Methoxypsoralen on Cytochrome P450 2A6 (CYP2A6) Allelic Variants CYP2A6*15, CYP2A6*16, CYP2A6*21 and CYP2A6*22: Differential Susceptibility Due to Different Sequence Locations of the Mutations

Human cytochrome P450 2A6 (CYP2A6) is a highly polymorphic isoform of CYP2A subfamily. Our previous kinetic study on four CYP2A6 allelic variants (CYP2A6*15, CYP2A6*16, CYP2A6*21 and CYP2A6*22) have unveiled the functional significance of sequence mutations in these variants on coumarin 7-hydroxylation activity. In the present study, we further explored the ability of a typical CYP2A6 inhibitor, 8-methoxypsoralen (8-MOP), in inhibition of these alleles and we hypothesized that translational mutations in these variants are likely to give impact on 8-MOP inhibitory potency. The CYP2A6 variant and the wild type proteins were subjected to 8-MOP inhibition to yield IC50 values. In general, a similar trend of change in the IC50 and Km values was noted among the four mutants towards coumarin oxidation. With the exception of CYP2A6*16, differences in IC50 values were highly significant which implied compromised interaction of the mutants with 8-MOP. Molecular models of CYP2A6 were subsequently constructed and ligand-docking experiments were performed to rationalize experimental data. Our docking study has shown that mutations have induced enlargement of the active site volume in all mutants with the exception of CYP2A6*16. Furthermore, loss of hydrogen bond between 8-MOP and active site residue Asn297 was evidenced in all mutants. Our data indicate that the structural changes elicited by the sequence mutations could affect 8-MOP binding to yield differential enzymatic activities in the mutant CYP2A6 proteins.
Volunteering as a community mental health educator: Positives and negatives for recovery

Abstract An advocacy role that is highly visible within the community is that of a consumer educator, when people with lived experience of mental illness use their personal experience to educate others in the community. This study investigated the positives and negatives for recovery of volunteering in an advocacy role as a consumer educator. A phenomenological qualitative research design was chosen, and semi-structured interviews were undertaken with 10 female consumer educators, aged between 20 and 59 years and with a wide range of diagnoses. Transcript s were analysed using a thematic analysis approach to identify themes within the data using a reiterative comparative procedure. The benefits of being a consumer educator far outweighed the negatives and four main themes emerged for the benefits: the unique value of peer support; the personal meaning gained from educating others about mental illness; the benefits of validation and catharsis through telling their story; and the skills gained. Negatives included feeling vulnerable during or after presentations, being fearful of stigma, and dealing with occasional challenges with co-presenters. This is one of the first studies of the effects on consumer educators of telling and re-telling their stories and ‘coming out’ in a public forum. It reveals substantial benefits for consumers in this advocacy role, but also shows that the role is not appropriate for all consumers and ongoing support in terms of screening, training, debriefing and peer support is vital.
SPECTRAL TECHNIQUES FOR PARTITIONING PLANTED RANDOM GRAPHS

This my final project paper for the class 18.S996: Algorithmic Aspects of Machine Learning, taught in Fall 2013 by Prof. Ankur Moitra. In this note, I will explain the spectral method for partitioning a graph as used in the following two papers: [1] N. Alon, M. Krivelevich, and B. Sudakov, Finding a large hidden clique in a random graph. [4] F. McSherry, Spectral partitioning of random graphs. In [1], the problem is to recover a planted clique of size c √ n in a random graph G(n, 1/2). That is, we first generate a random graph G(n, 1/2), and then randomly put in a clique of size c √ n, and the algorithmic goal is to recover this clique. In [4], variations and extensions of this planted clique problem are considered, including planted bisection and k-coloring. In each case, the graph is generated by first partitioning the vertices into parts of prescribed size (the algorithm doesn’t know which vertices belong to which partition) and then edges are places between parts and within parts using certain prescribed probabilities. The goal is to recover the original partition given the resulting random graph. In [4], McSherry considers probabilities that depend on n, the size of graph, whereas in [1], only the constant 1/2 probability is considered. These problems are all variations of classical NP-hard optimization problems which are even hard to approximate. However, the planted versions turn out to be more amenable, at least in certain parameter regimes. Note that our goal is to recover the planted object/partition, and not necessarily to solve the optimization problem (e.g., finding the largest clique), although these two goals can coincide (as they do in the case of planted clique, since the largest clique in G(n, 1/2) has size (2 + o(1)) log2 n). I will give only a very rough sketch of the proof ideas, without giving much details or calculations.
Teleseismic Search for Slow Precursors to Large Earthquakes

Some large earthquakes display low-frequency seismic anomalies that are best explained by episodes of slow, smooth deformation immediately before their high-frequency origin times. Analysis of the low-frequency spectra of 107 shallow-focus earthquakes revealed 20 events that had slow precursors (95 percent confidence level); 19 were slow earthquakes associated with the ocean ridge-transform system, and 1 was a slow earthquake on an intracontinental transform fault in the East African Rift system. These anomalous earthquakes appear to be compound events, each comprising one or more ordinary (fast) ruptures in the shallow seismogenic zone initiated by a precursory slow event in the adjacent or subjacent lithosphere.
A cone-based distributed topology-control algorithm for wireless multi-hop networks

The topology of a wireless multi-hop network can be controlled by varying the transmission power at each node. In this paper, we give a detailed analysis of a cone-based distributed topology-control (CBTC) algorithm. This algorithm does not assume that nodes have GPS information available; rather it depends only on directional information. Roughly speaking, the basic idea of the algorithm is that a node u transmits with the minimum power p/sub u,/spl alpha// required to ensure that in every cone of degree /spl alpha/ around u, there is some node that u can reach with power p/sub u,/spl alpha//. We show that taking /spl alpha/=5/spl pi//6 is a necessary and sufficient condition to guarantee that network connectivity is preserved. More precisely, if there is a path from s to t when every node communicates at maximum power then, if /spl alpha//spl les/5/spl pi//6, there is still a path in the smallest symmetric graph G/sub /spl alpha// containing all edges (u,v) such that u can communicate with v using power p/sub u,/spl alpha//. On the other hand, if /spl alpha/>5/spl pi//6, connectivity is not necessarily preserved. We also propose a set of optimizations that further reduce power consumption and prove that they retain network connectivity. Dynamic reconfiguration in the presence of failures and mobility is also discussed. Simulation results are presented to demonstrate the effectiveness of the algorithm and the optimizations.
Integrating contour and skeleton for shape classification

Shape analysis has been a long standing problem in the literature. In this paper, we address the shape classification problem and make the following contributions: (1) We combine both contour and skeleton (also local and global) information for shape analysis, and we derive an effective classifier. (2) We collect a challenging shape database in which there are 20 categories of animals, with each having 100 shapes. All these shapes are obtained from real images with a large variation in pose, viewing angle, articulation, and self-occlusion. (3) We emphasize the importance of having good representation for shape classification to address the unique characteristics of shape. A thorough experimental study is conducted showing significant improvement by the proposed algorithm over many of the state-of-the-art shape matching and classification algorithms, on both our dataset and the well-known MPEG-7 dataset [19]. In addition, we applied our algorithm for recognizing and classifying objects from natural images and obtained very encouraging results.
Moving Up a Gear: The Impact of Compressing Instructional Time into Fewer Years of Schooling

Policy-makers face a trade-off between the provision of higher levels of schooling and earlier labour market entries. A fundamental education reform in Germany tackles this trade-off by reducing high school by one year while leaving the total instructional time unchanged. Employing administrative data on all high school graduates in 2002-2013 in Germany, we exploit both temporal and regional variation in the implementation of the reform and study the overall effectiveness of this reform. We find that compressing the high school track by one year reduces the mean high school graduation age by about 10 months. The probability to repeat a grade level in the course of high school increases by 21 percent (3 percentage points), peaking in the final three years before graduation. However, the high school graduation rate is not affected. The results indicate the reform’s success in reducing the graduation age, though it stays behind its potential benefits for labour markets and social security schemes because of higher grade repetition rates.
Missing links? Problem drug use and social exclusion

In the late 1980s illicit drug use became a major social problem in the UK. Since then policy and practice has largely been shaped by psychological and medical perspectives that emphasize the physiological and psychological nature of dependence. Concerned by the limited impact in reducing the number of problem drug users, in 2000 the government shifted the emphasis away from voluntary treatment by the health and voluntary sector, towards coercive treatment, initially in the form of a Drug Treatment and Testing Order (DTTO). The Criminal Justice Interventions Programme (CJIP), a £447 million programme to ‘direct drug misusing offenders out of crime and into treatment’ (Home Office, 2004a: 29) further illustrates and reinforces this shift. This article argues that this shift in approach is also likely to founder, as it continues to be dominated by a narrow focus individuals and their drug dependence, and fails to adequately address the social context, nature and underlying causes of problem drug use.
Impact of Amplified Fragment Length Polymorphism Size Homoplasy on the Estimation of Population Genetic Diversity and the Detection of Selective Loci

AFLP markers are becoming one of the most popular tools for genetic analysis in the fields of evolutionary genetics and ecology and conservation of genetic resources. The technique combines a high-information content and fidelity with the possibility of carrying out genomewide scans. However, a potential problem with this technique is the lack of homology of bands with the same electrophoretic mobility, what is known as fragment-size homoplasy. We carried out a theoretical analysis aimed at quantifying the impact of AFLP homoplasy on the estimation of within- and between-neutral population genetic diversity in a model of a structured finite population with migration among subpopulations. We also investigated the performance of a currently used method (DFDIST software) to detect selective loci from the comparison between genetic differentiation and heterozygosis of dominant molecular markers, as well as the impact of AFLP homoplasy on its effectiveness. The results indicate that the biases produced by homoplasy are: (1) an overestimation of the frequency of the allele determining the presence of the band, (2) an underestimation of the degree of differentiation between subpopulations, and (3) an overestimation or underestimation of the heterozygosis, depending on the allele frequency of the markers. The impact of homoplasy is quickly diminished by reducing the number of fragments analyzed per primer combination. However, substantial biases on the expected heterozygosity (up to 15–25%) may occur with ∼50–100 fragments per primer combination. The performance of the DFDIST software to detect selective loci from dominant markers is highly dependent on the number of selective loci in the genome and their average effects, the estimate of genetic differentiation chosen to be used in the analysis, and the critical bound probability used to detect outliers. Overall, the results indicate that the software should be used with caution. AFLP homoplasy can produce a reduction of up to 15% in the power to detect selective loci.
Preservation of Recognizability for Weighted Linear Extended Top-Down Tree Transducers

An open question in [Fulop, Maletti, Vogler: Weighted extended tree transducers. Fundamenta Informaticae 111(2), 2011] asks whether weighted linear extended tree transducers preserve recognizability in countably complete commutative semirings. In this contribution, the question is answered positively, which is achieved with a construction that utilizes inside weights. Due to the completeness of the semiring, the inside weights always exist, but the construction is only effective if they can be effectively determined. It is demonstrated how to achieve this in a number of important cases.
SUS, an Object Reference Model for Distributing UNIX Super User Privileges

This paper describes a system administration tool which allows a user to run a command as root or as some other user after authenticating. Unlike most other commands of that ilk, SUS attempts to treat the command and its arguments as references to system objects, and allows for relatively powerful matching on the attributes of those objects to determine if the user should or should not be allowed to execute the desired command. In addition, SUS has a mode to help limit the number of setuid utilities needed to provide user services via the web.
Impact of optimization algorithms on hybrid indoor positioning based on GSM and Wi‐Fi signals

In the recent time indoor positioning becomes an extremely hot topic between researchers worldwide. This is mainly because of lack of available positioning solutions in the indoor environment and possibility to offer novel services based on location of users. Such services can also open new markets for service providers and thus increase their income. In this paper we will focus on application of optimization algorithms on performance of hybrid indoor positioning system, which utilize radio signals from both Global System for Mobile communication and Wi‐Fi networks simultaneously. The system is based on fingerprinting framework, which is widely used for indoor positioning because of its performance in strong multipath environment. Tests of the optimization algorithms were performed via simulations that were performed using simulation model created in Matlab environment. Copyright © 2016 John Wiley & Sons, Ltd.
The epistemic stance between the author and reader: A driving force in the cohesion of text and writing

This article explores the role of text cohesion in the comprehension and production of text. While most discourse models have considered the roles of the text features and the reader, the crucial role of writers’ epistemic stance has not been widely considered. The thesis explored here is that levels of cohesion emerge in text based on the epistemic stance of the author relative to the reader. Evidence is provided indicating that text genres (i.e. science, narrative) show compensatory relationships between different features related to text difficulty. For example, while science texts have more challenging words than do narratives, they tend to have higher cohesion and simpler syntax. These text profiles indicate that skilled writers have an awareness of readers’ needs. By contrast, less skilled writers seem to have less sensitivity to the interplay between textual dimensions and less audience awareness. For example, evidence is reviewed showing that more proficient essays are characterized by lower cohesion than less proficient essays: less skilled writers tend to use more cohesive cues (when they are likely unnecessary) than do more skilled writers. To the extent that an author understands the readers’ needs, the author has a more successful epistemic stance toward the reader. This stance is partially evidenced by the crucial role of cohesion in text comprehension and writing.
Investigation, treatment and monitoring of late-onset hypogonadism in males

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.
Modification of the peroxygenative: peroxidative activity ratio in the unspecific peroxygenase from Agrocybe aegerita by structure-guided evolution

Unspecific peroxygenase (UPO) is a heme-thiolate peroxidase capable of performing with high-selectivity C-H oxyfunctionalizations of great interest in organic synthesis through its peroxygenative activity. However, the convergence of such activity with an unwanted peroxidative activity encumbers practical applications. In this study, we have modified the peroxygenative:peroxidative activity ratio (P:p ratio) of UPO from Agrocybe aegerita by structure-guided evolution. Several flexible loops (Glu1-Pro35, Gly103-Asp131, Ser226-Gly243, Gln254-Thr276 and Ty293-Arg327) were selected on the basis on their B-factors and ΔΔG values. The full ensemble of segments (43% of UPO sequence) was subjected to focused evolution by the Mutagenic Organized Recombination Process by Homologous IN vivo Grouping (MORPHING) method in Saccharomyces cerevisiae. Five independent mutant libraries were screened in terms of P:p ratio and thermostability. We identified several variants that harbored substitutions at positions 120 and 320 with a strong enhancement in the P:p ratio albeit at the cost of stability. The most thermostable mutant of this process (S226G with an increased T50 of 2°C) was subjected to further combinatorial saturation mutagenesis on Thr120 and Thr320 yielding a collection of variants with modified P:p ratio and recovered stability. Our results seem to indicate the coexistence of several oxidation sites for peroxidative and peroxygenative activities in UPO.
Embedding Heterogeneous Data by Preserving Multiple Kernels

Heterogeneous data may arise in many real-life applications under different scenarios. In this paper, we formulate a general framework to address the problem of modeling heterogeneous data. Our main contribution is a novel embedding method, called multiple kernel preserving embedding (MKPE), which projects heterogeneous data into a unified embedding space by preserving cross-domain interactions and within-domain similarities simultaneously. These interactions and similarities between data points are approximated with Gaussian kernels to transfer local neighborhood information to the projected subspace. We also extend our method for out-of-sample embedding using a parametric formulation in the projection step. The performance of MKPE is illustrated on two tasks: (i) modeling biological interaction networks and (ii) cross-domain information retrieval. Empirical results of these two tasks validate the predictive performance of our algorithm.
STABILITY ANALYSIS OF SEPIC CONVERTER USING MATLAB/SIMULINK

DC-DC converter is a converter where we are regulating the input voltage to get the desired output voltage which is either greater than or equal to or less than the input voltage with positive or negative polarity. A lot of dc-dc converters are available in the world out of which SEPIC (Single-Ended Primary-Inductor Converter) converter is one of them. To analyse the converter, a lot of techniques are available. This paper presents the use of MATLAB/SIMULINK to study the stability of the converter. The state space technique is applied to this higher order converter and converted into transfer function. The reduced order technique is applied to the system and compared with the higher order system which gives approximate results for all type of analysis.
Phosphate‐Activated Glutaminase in Relation to Huntington's Disease and Agonal State

Abstract: Involvement of phosphate‐activated glutaminase in Huntington's disease and agonal state was investigated in caudate nucleus and frontal cortex from postmortem brains. In Huntington's disease the activities of phosphate‐activated glutaminase, glutamic acid decarboxylase, succinic dehydrogenase, choline acetyl‐transferase, and acetylcholinesterase were significantly reduced in the caudate nucleus, but not in the frontal cortex. The activity of phosphate‐activated glutaminase, and to a lesser extent of glutamic acid decarboxylase, was reduced in cases of terminal illness, as compared with cases of sudden death. Succinic dehydrogenase and choline acetyltransferase were reduced only in the few cases of prolonged and severe terminal illness. Enzyme activities of the caudate nucleus were more affected by agonal state than were those of frontal cortex. Results indicate that phosphate‐activated glutaminase could be a useful marker of neuronal damage due to agonal state, and that phosphate‐activated glutaminase and succinic dehydrogenase are reduced in Huntington's disease.
A rational function lens distortion model for general cameras

We introduce a new rational function (RF) model for radial lens distortion in wide-angle and catadioptric lenses, which allows the simultaneous linear estimation of motion and lens geometry from two uncalibrated views of a 3D scene. In contrast to existing models which admit such linear estimates, the new model is not specialized to any particular lens geometry, but is sufficiently general to model a variety of extreme distortions. The key step is to define the mapping between image (pixel) coordinates and 3D rays in camera coordinates as a linear combination of nonlinear functions of the image coordinates. Like a "kernel trick", this allows a linear algorithm to estimate nonlinear models, and in particular offers a simple solution to the estimation of nonlinear image distortion. The model also yields an explicit form for the epipolar curves, allowing correspondence search to be efficiently guided by the epipolar geometry. We show results of an implementation of the RF model in estimating the geometry of a real camera lens from uncalibrated footage, and compare the estimate to one obtained using a calibration grid.