The JaSpe specializer: BT-objects and the interprocedural aspect of the binding-time analysis algorithm

Статья посвящена частичным вычислениям, использующим offline-стратегию. Мощность этого метода решения задачи специализации программ во многом зависит от анализа времен связывания, который размечает программные конструкции как выполнимые либо невыполнимые на этапе специализации. Анализ времен связывания может использовать несколько вариантов разметки полей класса, зависящих от их использования в программе. Увеличивая число потенциальных оптимизаций, такая поливариантность по классам позволяет эффективно специализировать большее число программ. Наибольший эффект достигается на объектно/̄ориентированных языках, предполагающих создание большого количества различающихся по назначению экземпляров класса. Известные алгоритмы анализа времен связывания расширяются до поливариантности по классам и распространеняются их на объектно/̄ориентированный язык общего назначения. Новые методы реализованы в виде набора плагинов для Eclipse IDE, составляющих специализатор JaSpe для программ на Java.

The Interaction between DNA and Three Intercalating Anthracyclines Using Electrochemical DNA Nanobiosensor Based on Metal Nanoparticles Modified Screen-Printed Electrode

The screen-printed electrodes have gained increasing importance due to their advantages, such as robustness, portability, and easy handling. The manuscript presents the investigation of the interaction between double-strand deoxyribonucleic acid (dsDNA) and three anthracyclines: epirubicin (EPI), idarubicin (IDA), and doxorubicin (DOX) by differential pulse voltammetry on metal nanoparticles modified by screen-printed electrodes. In order to investigate the interaction, the voltammetric signals of dsDNA electroactive bases were used as an indicator. The effect of various metal nanomaterials on the signals of guanine and adenine was evaluated. Moreover, dsDNA/PtNPs/AgNPs/SPE (platinum nanoparticles/ silver nanoparticles/screen-printed electrodes) was designed for anthracyclines–dsDNA interaction studies since the layer-by-layer modification strategy of metal nanoparticles increases the surface area. Using the signal of multi-layer calf thymus (ct)-dsDNA, the within-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 0.58% and 0.73%, respectively, and the between-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 1.04% and 1.26%, respectively. The effect of binding time and concentration of three anthracyclines on voltammetric signals of dsDNA bases were also evaluated. The response was examined in the range of 0.3–1.3 ppm EPI, 0.1–1.0 ppm IDA and DOX concentration on dsDNA/PtNPs/AgNPs/SPE. Electrochemical studies proposed that the interaction mechanism between three anthracyclines and dsDNA was an intercalation mode.

Hierarchical Regulation of Autophagy During Adipocyte Differentiation

We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and the effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyte differentiation and evaluated the effect of the regulators on gene expression in terms of direction and magnitude. Then, we identified the overlap of the transcription factors and co-factors binding sites and targets. Finally, we built a chromatin states model based on the histone marks and studied their relation with the factors’ binding. Adipogenic factors differentially regulated autophagy genes as part of the differentiation program. Co-regulators associated with specific transcription factors and preceded them to the regulatory regions. Transcription factors differed in the binding time and location, and their effect on expression was either localized or long-lasting. Adipogenic factors disproportionately targeted genes coding for autophagy-specific transcription factors. To sum, a hierarchical arrangement between adipogenic transcription factors and co-factors drives the regulation of autophagy during adipocyte differentiation.

Enhanced type inference for binding-time analysis

In this paper we will be taking a look at type inference and its uses for binding-time analysis, dynamic typing and better error messages. We will propose a new binding-time analysis algorithm ℬ, which is a modification of an already existing algorithm by Gomard [4], and discuss the speed difference.

The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands. In this review, AhR is discussed with a focus on (i) the role of AhR in osteoclast differentiation and function and (ii) the mechanisms of AhR signaling in inhibiting or promoting osteoclastogenesis. These findings facilitate an understanding of the role of AhR in the functional regulation of osteoclasts and in osteoclast-induced bone destructive conditions such as rheumatoid arthritis and cancer.

Probing fibronectin adsorption on chemically defined surfaces by means of single molecule force microscopy

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) and a quartz crystal microbalance (QCM) were respectively employed to probe interfacial characteristics of fibronectin fragment FNIII8–14 and full-length fibronectin (FN) on CH3–, OH–, COOH–, and NH2-terminated alkane-thiol self-assembled monolayers (SAMs). Force-distance curves acquired between hexahistidine-tagged FNIII8–14 immobilised on trisNTA-Ni2+ functionalized AFM cantilevers and the OH and COOH SAM surfaces were predominantly ‘loop-like’ (76% and 94% respectively), suggesting domain unfolding and preference for ‘end-on’ oriented binding, while those generated with NH2 and CH3 SAMs were largely ‘mixed type’ (81% and 86%, respectively) commensurate with unravelling and desorption, and ‘side-on’ binding. Time-dependent binding of FN to SAM-coated QCM crystals occurred in at least two phases: initial rapid coverage over the first 5 min; and variably diminishing adsorption thereafter (5–70 min). Loading profiles and the final hydrated surface concentrations reached (~ 950, ~ 1200, ~ 1400, ~ 1500 ng cm−2 for CH3, OH, COOH and NH2 SAMs) were consistent with: space-filling ‘side-on’ orientation and unfolding on CH3 SAM; greater numbers of FN molecules arranged ‘end-on’ on OH and especially COOH SAMs; and initial ‘side-on’ contact, followed by either (1) gradual tilting to a space-saving ‘end-on’ configuration, or (2) bi-/multi-layer adsorption on NH2 SAM.

Roles of motor on-rate and cargo mobility in intracellular transport

Molecular motors like kinesin are critical for cellular organization and biological function including in neurons. There is detailed understanding of how they move and how factors such as applied force and the presence of microtubule-associated proteins can alter this single-motor travel. In order to walk, the cargo-motor complex must first attach to a microtubule. This attachment process is less studied. Here, we use a combination of single-molecule bead experiments, modeling, and simulation to examine how cargos with kinesin-1 bind to microtubules. In experiment, we find that increasing cargo size and environment viscosity both signficantly slow cargo binding time. We use modeling and simulation to examine how the single motor on rate translates to the on rate of the cargo. Combining experiment and modeling allows us to estimate the single motor on rate as 100 s−1. This is a much higher value than previous estimates. We attribute the difference between our measurements and previous estimates to two factors: first, we are directly measuring initial motor attachment (as opposed to re-binding of a second motor) and second, the theoretical framework allows us to account for missed events (i.e. binding events not detected by the experiments due to their short duration). This indicates that the mobility of the cargo itself, determined by its size and interaction with the cytoplasmic environment, play a previously underestimated role in determining intracellular transport kinetics.

Karakteristik Marshall pada Campuran Aspal Dingin dengan Asbuton Akibat Dari Penggunaan Aditif Wetfix-BE

West Nusa Tenggara Province consists of two main islands namely Lombok and Sumbawa. Regency Roads on Lombok Island, especially rural roads, has been severely damaged due to lack of routine maintenance. The types of damage that occur are cracks, small holes, and even large pools that endanger road users. This study aims to obtain a mixture of new materials in order to obtain an easy and fast repair method without reducing the quality during its intended life. In the meantime, repairing with CAD (cold asphalt mixture) requires curing time of 3x24 hours to achieve standard material quality with Marshall Characteristics according to the 2010 Bina Marga Specifications. This study combines CAD using BP (rejuvenating agent) and Wetfix-BE additive to get optimal results without curing process. The BP used is asphalt mixture, kerosene, and bunker oil stirred in a mixing machine into one unit. The results showed the optimum concentration of this mixture was 0.3% wet-be additive, 4.50% BP in CAD with asbuton proportion of 25%. In the fatigue test with a cyclic loading of 100 kPa, the pavement mixture is able to resist a fully loaded truck of 7731 times. In conclusion, this mixture combination is able to speed up the asphalt binding time by making briquettes according to the 2018 Highways Specifications without going through the long curing process.

The JaSpe specializer: an algorithm of intra-procedural binding time analysis for programs in Java language subset

Анализ времени связывания в частичных вычислениях, нацеленных на оптимизацию программ, разделяет программные конструкции на статические и динамические. Статические конструкции исполняются специализатором, а динамические переходят в результирующую программу. Частичные вычисления применяются в основном для нетривиальной компиляции программ без компилятора, при наличии лишь интерпретатора и специализатора. Эффективность их существенно зависит от качества разметки программы, получаемой в результате анализа времени связывания. Статья посвящена особенностям алгоритма анализа времени связывания специализатора JaSpe, разрабатываемого авторами данной публикации для широко распространенного объектно/ориентированного языка Java. Она содержит основные понятия, использованные при реализации анализа времени связывания, внутрипроцедурную версию алгоритма и обсуждение деталей анализа конструкций, использующих ссылочные типы данных. Алгоритм отличается от предшествующих аналогов, из числа работающих с программами на объектно-ориентированных языках, нетривиальной обработкой конструкций ветвления (if, switch), циклов (for, while, do) и блочных инструкции, которые содержат последовательность других инструкций. От аналогичных алгоритмов, работающих с императивными и функциональными языками, он отличается использованием BT-объектов, которые позволяют получать более точную разметку — c большей долей статических конструкций — при обработке объектно-ориентированных программ. Алгоритм ориентирован на интерактивность и удобочитаемость результатов.

Study of Time-dependent Interaction of ZnO Nanoparticles with Sucrose and Honey Molecules for Biomedical Applications

Background: Nanoparticles are in the forefront of research due to their unique properties that find possible applications from optoelectronics to medical technology. It is also reported that nanoparticles can interact with the living cells and can selectively destroy the cells. Researchers are thus interested to find a way by which the drugs will be attached to the nanoparticles, go to the target site and destroy the infected cells. Before that, it is very much important to understand the interaction of nanoparticles with the blood, plasma and other biological cells that exists in the blood. It is also very essential to understand how the nanoparticles interact with the absorbed sucrose in the cell. Objective: Our objective in this research is to investigate the interaction of ZnO nanoparticles with sucrose and honey sugar to understand the basic interaction mechanism. It will also enable us to find a way of stabilizing body sucrose and glucose level. Methods: We have followed a simple chemical synthesis method to prepare ultrafine ZnO nanoparticles. Then the interaction of ZnO nanoparticles with sucrose and honey sugar was investigated as a function of time using UV-visible spectroscopy to understand the basic interaction mechanism. Results: Well grown ZnO nanoparticles were found to form of crystallite size ~38 nm. The band gap was calculated from the absorption spectra and was found to be ~ 3.9 eV. This band gap enhancement indicates that the sizes of the nanoparticles are very small. The decrease of absorption with time indicates that the ZnO nanoparticles interact with the sugar molecule. Sucrose molecules are polar. Hence there is electrostatic attraction between the sucrose molecules and ZnO molecules resulting in the sucrose-ZnO composite system. On increasing the interaction time more and more sucrose molecules will cover the ZnO nanoparticles by forming ZnO-sucrose corona. The interaction time constant i.e., the binding time of sucrose molecule with the surface of ZnO nanoparticles, t1 was found to be 27.7127 min and is 29.59 min for honey. The results indicate an association process to form corona of ZnO nanoparticles with sucrose and honey molecules. Conclusion: We have successfully synthesized ultrafine ZnO nanoparticles of high band gap. The synthesized nanoparticles interact with the sucrose and honey molecules and form corona. This study is very important in understanding the interaction mechanism on nanoparticles with the biomolecules for possible drug delivery applications.