Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of age on in vitro midazolam biotransformation in male CD-1 mouse liver microsomes.

To study age-related changes in drug metabolism, we examined the in vitro biotransformation of midazolam (MDZ), a human cytochrome P-450 (CYP) 3A substrate, using liver microsomes from three age groups of male CD-1 mice ranging from 6 weeks to 2 years old. MDZ was metabolized to two major products, alpha-OH- and 4-OH-MDZ, which were quantified by HPLC. For both metabolites, V(max) values were reduced in old livers (P <.05), while K(m) values did not change with age. The net intrinsic clearance (the sum of V(max)/K(m) for both pathways) also was reduced in the old animals (P <.05). The capacity of ketoconazole, a CYP3A inhibitor in humans, to inhibit the biotransformation of MDZ and of alprazolam, another human CYP3A substrate, did not differ significantly with age. At 100 microM alprazolam, 0.5 microM ketoconazole inhibited metabolite formation by >80%. At 30 microM MDZ, 2.5 microM ketoconazole impaired 4-OH-MDZ formation by 88%, whereas it reduced alpha-OH-MDZ formation by only 46%. Immunoinhibition studies with polyclonal anti-rat CYP3A1/2 and CYP2C11 antibodies confirmed that 4-OH-MDZ formation was largely CYP3A-dependent, while alpha-OH-MDZ formation was mediated by CYP3A and -2C isoforms. Western blot analysis revealed decreased microsomal content of CYP3A in old livers. Net intrinsic clearance of MDZ was correlated with total CYP3A content (P <.001). These results demonstrate a reduction in MDZ biotransformation in old male mice, which may be attributable, in part, to decreased CYP3A content in old livers. Changes in expression and activity of CYP2C isoforms also may contribute to age-related changes in MDZ biotransformation, but this requires more investigation.
Optimization on Seperator Trees

Given a chordal graph G, and a class of subgraphs H of G, we investigate the problem of finding an element H ∈ H which minimizes a function f : H → R. We show that when f satisfies a decomposability criterion, and when H admits what we call an efficiently decomposable configuration space with respect to f , then this optimization problem can be solved in polynomial time. We give a dynamic programming formulation for solving this problem, which uses a representation of of G called a seperator-tree. The seperator-clique tree is very closely related to the clique-tree representation for G, and we give a procedure for constructing a seperator-clique tree from a clique-tree. Gavril [1] and Tarjan [2] have used graph separation properties to solve several combinatorial optimization problems when the size of the minimal separators in the graph is bounded. Our technique is an extension of theirs, and it does not require the minimal separators of G to be of bounded size. We give examples to show that this framework can be used to solve a number of problems in machine learning and statistics that require the reduction of complexity of graphical models.
Gradient-based algorithms with applications to signal-recovery problems

This chapter presents in a self-contained manner recent advances in the design and analysis of gradient-based schemes for specially structured smooth and nonsmooth minimization problems. We focus on the mathematical elements and ideas for building fast gradient-based methods and derive their complexity bounds. Throughout the chapter, the resulting schemes and results are illustrated and applied on a variety of problems arising in several specific key applications such as sparse approximation of signals, total variation-based image processing problems, and sensor location problems.
Integrality, complexity and colourings in polyhedral combinatorics

Doctoral School: Mathematics Director: Miklos Laczkovich, Member of the Hungarian Academy of Sciences Doctoral Program: Applied Mathematics Director: Gyorgy Michaletzky, Doctor of Sciences Advisor: Andras Frank, Doctor of Sciences, Professor Co-advisor: Tamas Kiraly, Ph.D. Affiliation: Department of Operations Research, Eotvos Lorand University and Egervary Research Group on Combinatorial Optimization, Budapest, Hungary
Fusion of heterogeneous features via cascaded on-line boosting

In this paper, we employ the recent on-line boosting framework to fuse heterogeneous features for object detection and tracking in a video surveillance application. Detection and tracking are treated as a classification problem by an ensemble of weak classifiers built on heterogeneous feature types and updated on-line. We extend the on-line boosting framework by proposing an algorithm that builds a cascade of classifiers dynamically. The procedure takes into account both the error and the computational requirements of the available features and populates the levels of the cascade accordingly to optimize the detection rate while retaining real-time performance. We show the effectiveness of employing different features on real-world video sequences.
Antitumor Efficacy of bcl-2 and c-myc Antisense Oligonucleotides in Combination with Cisplatin in Human Melanoma Xenografts: Relevance of the Administration Sequence

Purpose: bcl-2 and c-myc oncogenes are frequently overexpressed in different human tumors, including melanoma. Here, we evaluate the combined efficacy of two antisense oligonucleotides targeting bcl-2 mRNA (ODN bcl-2) and c-myc mRNA (ODN c-myc) in combination with cis-diammine dichloroplatinum (cisplatin, DDP) on three human melanoma lines (LM, NG, and M20). Experimental Design: Two different sequences were designed to treat tumor-bearing mice: in the first one, ODN bcl-2 at a dose of 0.2 mg/day ×4, followed by DDP given i.p. at a dose of 3.3 mg/kg/day ×3 and ODN c-myc i.v. at 0.5 mg/day ×7, whereas the other sequence consisted of ODN c-myc given as first agent followed by DDP and ODN bcl-2 at the same doses. Mice received three complete cycles of treatment in 1-week intervals. Results: The treatment sequence with ODN bcl-2/DDP/ODN c-myc combination completely inhibited growth in NG tumor and induced a 35-day delay in LM tumor growth. In contrast, the M20 tumor growth was unaffected by the combination. A discrete amount of c-Myc and bcl-2 protein expression in both LM and NG tumors was detected, whereas no detectable levels of the two proteins were observed in M20 tumors. Compared with the other combination, the sequence (ODN bcl-2/DDP/ODN c-myc) produced the most effective results, producing a significant decrease in bcl-2 and c-Myc protein expression, which in turn significantly increased the survival of NG- and LM-bearing mice, with 4 mice out of 11 and 1 out of 7 mice being cured, respectively. Finally, this combination increased the apoptotic rate and produced an antiangiogenetic effect. Conclusions: These results show that an antisense approach to the treatment of melanoma xenografts overexpressing either bcl-2 or c-myc oncogenes represents a successful strategy to improve the response to chemotherapy in melanoma, with particular attention to the treatment sequence.
Human IRIS Identification Via Low-Complexity Circular Periodicity Transform

In this paper, we propose a low-complexity circular periodicity transform (CPT) for human iris identification. The proposed CPT enhances the standard periodicity transform by enabling the extraction of a wide spectrum of periodic patterns hidden in human iris. A computation-efficient architecture is developed for accurate iris identification with minimal hardware cost. The CPT-based iris identification system achieves up to 99.2% recognition rates with 21.8% - 56.2% reduction in computation complexity as compared with the standard periodicity transform. The proposed CPT in combination with architecture optimizations address the challenges in single-chip implementation of biometric systems
Comptonization in the vicinity of the black hole horizon

Using a Monte Carlo method, we derive spectra arising from Comptonization taking place close to a Kerr black hole. We consider a model consisting of a hot thermal corona Comptonizing seed photons emitted by a cold accretion disc. We find that general relativistic effects are crucial for the emerging spectra in models, which involve significant contribution of radiation produced in the black hole ergosphere. As a result of this contribution, spectra of hard X-ray emission produced in the vicinity of a rapidly rotating black hole strongly depend on the inclination of the line of sight, with larger inclinations corresponding to harder spectra. Remarkably, such anisotropy could be responsible for properties of the X-ray spectra of Seyfert galaxies, which appear to be intrinsically harder in type 2 objects than in type 1, as reported recently.
A model for parallel evolutionary search

A parallel search technique for improving evolutionary algorithms is proposed. The method is based on a new philosophy of applying search operators. Two search operators compete for being applied. One is a hybrid operator (recombination plus mutation) and the other is pure mutation operator. The aim of the proposed technique is to maintain a good equilibrium between the exploration and the exploitation of the search space. Experimental results prove that the parallel search outperforms the standard way of applying search operators. A new quality measure for search operators is also proposed.
A proposed tutoring system to support the learning of computer programming: Case Study

The deployment of technology across the globe towards efficient learning environments is growing rapidly. In the United Kingdom, for example, the government is investing 1.1 million pounds towards primary and secondary school early programming lessons; with similar investments happening in other countries. The ideology behind this push is to strengthen the link between the younger generation and the technological growth that will continue to have an ever increasing impact upon their lives and to fuel the pace of innovation. One of the core themes of this area is that of computer programming, which has been overlooked at this level of education until recently. This paper will convey this research into the development of tutoring systems for supporting the learning of computer programming in early years schooling. It will also discuss in depth the significant statistical results of the experimental study, which were conducted in one the UK primary schools. Fifty-two pupils participated in this experimental study, which were divided into three groups comprising of different ages and skill sets.
The embodied mind: A journey through the “soma” to reach the “psyche”

Background: Recent studies have confirmed a significant comorbidity between eating disorders and self-harm; they linked the presence of self-harm to a more severe and treatment-resistant eating disorder symptomatology. Difficulties with impulse-control were suggested to mediate this association. The present study explored another variable believed to be involved: mentalising. Method: A cross-sectional, questionnaire-based, between-groups design was employed and a measure of mentalising was compared in individuals presenting with eating disorders and in individuals presenting with eating disorders and concurrent self-harm. Both groups were compared with a control group. Results: Findings suggested that individuals with concurrent presentations reported less mentalising ability compared to individuals without concurrent difficulties. In addition, both groups significantly differed from the control group. Conclusions: Results are discussed in relation to clinical implications.
Design and Implementation of Hybrid Shingled Recording RAID System

Shingled write disks (SWDs) adopt shingled magnetic recording (SMR) to overcome the density limit faced in the conventional hard disk drives (HDDs) and RAID5 provide high performance and high reliability for reasonable cost. Meanwhile Flash memory based Solid State Drives (SSDs) are becoming an important part of computer storage hierarchy to significantly improve performance and energy efficiency. In this work, we present a novel shingled recording RAID, which turned the traditional disks in RAID into SWDs with considerable performance. We implemented the storage system in 3 models: first, we take the SSD as the cache of RAID on the top of storage system, second, we regarded SSDs as caches of every single SWD, in the third way, we have SSDs as caches for both RAID and every single SWD. We designed a backup strategy for model 1 and a hot data select algorithm for cache. We have implemented SWDs RAID on Linux system. Extensive experiments have been carried out to evaluate the three model of SWDs RAID. Experimental results show that shingled recording RAID could maintain the performance of traditional RAID even with 1.83% performance improvement by model 1. While the backup policy improve the reliability of SWDs RAID in return for 2.03% IOPS decrease.
Application of a symbolic-connectionist approach for the design of a highly interactive documentary database interrogation system with on-line learning capabilities

The NOMAD system is a documentary database interrogration system based on a symbolico-connectionist approach. NOMAD makes use of the synthesis capabilities and flexibility inherent in this type of approach to increase its processing power as compared as compared to existing systems while proposing new operating modes directly accessible to a large number of users: •NOMAD manages multiple synthetic type views on its documentary contents in the form of neural topographies acting as case-memories as well as elaborated thematic browsing tools. •NOMAD manages a session memory based on the neural model of the novelty detector with the following three functions: cumulative recording of user need, managing user contradictions and proposing new orientations. •NOMAD also has extended learning capabilities, enabling it to improve its performance in the long term. In the introduction of this article, we justify the modelling choices made for NOMAD. The system will then be described in detailed, stressing the new possibilities regarding help in query formulation and improvement in retrieval performance. The evaluation campaign and the numerous evolution perspectives provided by the model are described in the final section.
Comparison between Multi-Layer Perceptron and Radial Basis Function Networks for Sediment Load Estimation in a Tropical Watershed

Prediction of highly non-linear behavior of suspended sediment flow in rivers has prime importance in environmental studies and watershed management. In this study, the predictive performance of two Artificial Neural Networks (ANNs), namely Radial Basis Function (RBF) and Multi-Layer Perceptron (MLP) were compared. Time series data of daily suspended sediment discharge and water discharge at the Langat River, Malaysia were used for training and testing the networks. Mean Square Error (MSE), Normalized Mean Square Error (NMSE) and correlation coefficient (r) were used for performance evaluation of the models. Using the testing data set, both models produced a similar level of robustness in sediment load simulation. The MLP network model showed a slightly better output than the RBF network model in predicting suspended sediment discharge, especially in the training process. However, both ANNs showed a weak robustness in estimating large magnitudes of sediment load.
Have Your Data and Query It Too: From Key-Value Caching to Big Data Management

Couchbase Server is a rethinking of the database given the current set of realities. Memory today is much cheaper than disks were when traditional databases were designed back in the 1970's, and networks are much faster and much more reliable than ever before. Application agility is also an extremely important requirement. Today's Couchbase Server is a memory- and network-centric, shared-nothing, auto-partitioned, and distributed NoSQL database system that offers both key-based and secondary index-based data access paths as well as API- and query-based data access capabilities. This is a major change from Couchbase's roots; in its early days, its focus was entirely on high performance and highly available key-value (memcache) based caching. Customer needs and competitive pressures in the evolving non-relational database market also accelerated this change. This paper describes the architectural changes needed to address the requirements posed by next-generation database applications. In addition, it details the implementation of such an architecture using Couchbase Server and explains the evolution of Couchbase Server from its early roots to its present form. Particular attention is paid to how today's Couchbase Server cluster architecture is influenced by the memory-first, high-performance, and scalability demands of typical customer deployments. Key features include a layer-consolidated cache, a consistency-controllable interplay between updates, indexes, and queries, and a unique "multi-dimensional" approach to cluster scaling. The paper closes with a look at future plans for supporting semi-structured operational data analytics in addition to today's more OLTP-like, front-facing use cases.
Longitudinal study of a dual-factor model of mental health in Chinese youth

By incorporating psychopathology and subjective well-being (SWB), the dual-factor model of mental health (DFM) can comprehensively measure psychological health. We examined the utility of the DFM among 1,293 Chinese adolescents (Grades 7–12). Furthermore, we examined the dynamics of mental health group membership via a two-wave longitudinal study of 531 students. SWB, psychopathology, affective self-regulatory efficacy, academic self-efficacy, and academic emotions were measured via self-report scales. Mental health group membership was determined according to combinations of high or low SWB and high or low psychopathology. The DFM was supported by our identification of its four constituent groups (i.e. complete mental health, vulnerable, troubled, and symptomatic but content). Significant group differences were found in affective self-regulatory efficacy, academic self-efficacy, and academic emotions, with clear contrasts observed between adolescents with complete mental health and their vulnerable peers, as well as between troubled adolescents and their symptomatic but content peers. Moreover, youth with complete mental health demonstrated the highest stability and troubled youth the lowest, whereas vulnerable youth had the highest rates of transitioning into both the complete mental health and troubled groups. Implications for practice are explored within the context of screening and intervention.
Applying ISO-Space to Healthcare Facility Design Evaluation Reports

This paper describes preliminary work on the spatial annotation of textual reports about healthcare facility design to support the long-term goal linking of report content to a three-dimensional building model. Emerging semantic annotation standards enable formal description of multiple types of discourse information. In this instance, we investigate the application of a spatial semantic annotation standard at the building-interior level, where most prior applications have been at inter-city or street level. Working with a small corpus of design evaluation documents, we have begun to apply the ISO-Space specification to annotate spatial information in healthcare facility design evaluation reports. These reports present an opportunity to explore semantic annotation of spatial language in a novel situation. We describe our application scenario, report on the sorts of spatial language found in design evaluation reports, discuss issues arising when applying ISO-Space to building-level entities and propose possible extensions to ISO-Space to address the issues encountered.
Using Temporal-Difference Reinforcement

Probability theory represents and manipulates uncertainties, but cannot tell us how to behave. For that we need utility theory which assigns values to the usefulness of different states, and decision theory which concerns optimal rational decisions. There are many methods for probability modeling, but few for learning utility and decision models. We use reinforcement learning to find the optimal sequence of questions in a diagnosis situation while maintaining a high accuracy. Automated diagnosis on a heart-disease domain is used to demonstrate that temporal-difference learning can improve diagnosis. On the Cleveland heart-disease database our results are better than those reported from all previous methods.
GaN-based radio-frequency planar inter-digitated metal-insulator-semiconductor varactors

The first demonstration of radio-frequency planar inter-digitated metal-insulator-semiconductor (PIDMIS) varactors fabricated on AlGaN/GaN heterostructures is reported. The PIDMIS varactors achieved good quality factor (Q-factor) and tuning range. The Q-factor of PIDMIS varactors is discussed, based on a physical equivalent circuit which takes into account the capacitance of the active channel, fixed insulator capacitance, parasitic resistances and leakage current through the substrate. The experimental data shows that for identical substrate structures, the quality factor varies with different design parameters.
Size matters: relationships between body size and body mass of common coastal, aquatic invertebrates in the Baltic Sea

Background Organism biomass is one of the most important variables in ecological studies, making biomass estimations one of the most common laboratory tasks. Biomass of small macroinvertebrates is usually estimated as dry mass or ash-free dry mass (hereafter ‘DM’ vs. ‘AFDM’) per sample; a laborious and time consuming process, that often can be speeded up using easily measured and reliable proxy variables like body size or wet (fresh) mass. Another common way of estimating AFDM (one of the most accurate but also time-consuming estimates of biologically active tissue mass) is the use of AFDM/DM ratios as conversion factors. So far, however, these ratios typically ignore the possibility that the relative mass of biologically active vs. non-active support tissue (e.g., protective exoskeleton or shell)—and therefore, also AFDM/DM ratios—may change with body size, as previously shown for taxa like spiders, vertebrates and trees. Methods We collected aquatic, epibenthic macroinvertebrates (>1 mm) in 32 shallow bays along a 360 km stretch of the Swedish coast along the Baltic Sea; one of the largest brackish water bodies on Earth. We then estimated statistical relationships between the body size (length or height in mm), body dry mass and ash-free dry mass for 14 of the most common taxa; five gastropods, three bivalves, three crustaceans and three insect larvae. Finally, we statistically estimated the potential influence of body size on the AFDM/DM ratio per taxon. Results For most taxa, non-linear regression models describing the power relationship between body size and (i) DM and (ii) AFDM fit the data well (as indicated by low SE and high R2). Moreover, for more than half of the taxa studied (including the vast majority of the shelled molluscs), body size had a negative influence on organism AFDM/DM ratios. Discussion The good fit of the modelled power relationships suggests that the constants reported here can be used to quickly estimate organism dry- and ash-free dry mass based on body size, thereby freeing up considerable work resources. However, the considerable differences in constants between taxa emphasize the need for taxon-specific relationships, and the potential dangers associated with ignoring body size. The negative influence of body size on the AFDM/DM ratio found in a majority of the molluscs could be caused by increasingly thicker shells with organism age, and/or spawning-induced loss of biologically active tissue in adults. Consequently, future studies utilizing AFDM/DM (and presumably also AFDM/wet mass) ratios should carefully assess the potential influence of body size to ensure more reliable estimates of organism body mass.