Information security means protecting information and information systems from unauthorized access, use, disclosure, disruption, modification or destruction, to assure confidentiality, availability and integrity. The new trends of telecommunications of the last year is the move towards the trasmission of voice over traditional packet switched IP network, voice over IP, that has become a valid alternative to traditional public circuit-switched telephone network and then the convergence of the communication systems, through the next generation networks definition. This environment presents many security problems and significant security challenges. The voice over IP system increase these with those normally tie to IP network. Along with a several benefits of voice over IP, there are new security threats for exchanged informations. This paper analyzes the security issues of the communication systems, starting from the traditional public switched telephone network toward the new next generation network. Then, with this paper, we want to introduce a process approach to manage the security, based on epidemiological model. This model is characterized by three steps, Analysis, Assessment and Management, and it can be applied to a general information security system, to identify, assess and classify the information assets, the processes concerning it, vulnerabilities of each level and common threats. Finally we evaluate the risk and the probability of damage that can crash the system or part of this and propose a model of failure time analysis. The target of this analysis is to calculate the extent of the risk function in order to understand the state and the degree of security of our system, by studying the statistics of failure and to ensure highest degree of security optimizing the business strategic decisions and information and communication technology security economic investments. The methodology is designed to be applied in the future to communication systems, more specifically. This does not exclude the application of this methodology in other areas of interest (biomedical or economical areas) to understand, formalize and solve problems of similar nature.


Introduction: There are frequent changes in the supply of female child population, especially in aesthetic sports athletes by pressure to maintain a body. Objectives: The aim was to evaluate nutritional, anthropometric and weight perception aspects of girls who perform rhythmic gymnastics. Methods: 25 gymnast girls were compared to 25 control girls (control). Anthropometric assessment was done by ISAK protocol and nutrition through a seven-day dietary record; as well as a quantitative and qualitative assessment of dietary intake by the DIAL software. Nutritional assessment was performed using a seven days dietary record. A quantitative and qualitative assessment of food intake was conducted, using DIAL software. An ad hoc questionnaire to assess their perception of weight was completed. Results: Anthropometric data showed no signifi cant differences between the study groups except for skinfolds and fat percentage, which was statistically lower in gymnast girls. Energy intake (1,413 ± 283 kcal/day) of gymnasts was lower than recommended by the Food and Nutrition Board, according to their age. Distribution of macronutrients was in the range of normal values (10-30% proteins, 45-65% carbohydrates, 20-35% fat). 32% of gymnasts and 36.4% of control girls felt they should weigh less. Conclusion: Considering the activity carried out by gymnasts, their energy requirements should conform to it, as this will contribute to their development and growth, and also to better perform their activity. Gymnasts' food consumption is far from a balanced diet. No different behaviors were observed in the perception of weight between the two groups. Resumen


Dr. Ismā'īl Rājī al Fārūqī (1339-1406 A.H/1921-1986 A.C) is widely recognized as an authority on Islam and comparative religion. Dr. al Fārūqī was a dedicated and active academician. His educational training in Philosophy took place at Indiana and Harvard University. He also engaged in the post-graduate study of Islam at al-Azhar University and Christianity and Judaism at McGill University. He co-founded the International Institute of Islamic Thought (IIIT) and the Association of Muslim Social Scientists (AMSS). Among his significant intellectual and academic contributions is his consistent emphasis on the Islamization of knowledge and result-oriented inter-faith dialogues. The present book, Toward Islamic English, extends the same discourse on the Islamization of knowledge. However, the paradigm in which the book's theme is described is more academic and relates to the methodological dimensions of studying Islamic Studies as an academic discipline.


A robust adaptive chattering-free sliding mode (ACFSM) control method for electronic throttle (ET) system is proposed in this paper. It is well known that nonlinearities in the throttle system including friction, return-spring, limp-home (LH) and gear backlash affect the control accuracy of the throttle valve. Compared with the traditional sliding mode control methods, the ACFSM control not only overcomes the influence of nonlinearities and parameter uncertainties in the ET system, but also eliminates chattering in nature such that excellent throttle tracking performance and robustness are maintained. The proposed ACFSM control method is superior to the traditional sliding mode control in the following two aspects: 1) The chattering-free sliding mode control method is able to attenuate the control chattering without weakening the output tracking performance and robustness. 2) The upper bounds of the uncertainty and disturbance are not required any more in control design. They are online estimated by the adaptive law in the sense of Lyapunov. Moreover, due to the difficulty in selecting proper control parameters, the genetic algorithm (GA) is introduced to optimate the control parameters for the ACFSM controller prior to practical implementation. The comparative experimental results are given to demonstrate the excellent control performance of the proposed ACFSM control.


This study surveyed attitudes, behaviors, social norms, and perceived control among the populations of students at three high schools in downtown Toronto, Ontario, Canada. The results showed a pattern of hesitancy to cycle on the part of female high school students compared with their male counterparts. Young women reported less access to a bicycle, less comfort or confidence in riding, more fear associated with cycling, and less ability to decide independently how to travel to school. The study identified two important variables that were likely associated with young women's smaller participation in cycling to school: overall cycling mode share and ability to decide their travel mode independently. The former variable tracked findings for the general population, and the latter appeared to have been associated with the proximity of immigration, as families might have brought associations of danger to independent female travelers from their countries of origin or perceived new dangers in Canada. While the former association is well established, the latter hypothesis warrants further research.


Fa ys~s has recently become a very efficient pre-chromatographic treatment technique for the determination of small and medium molecules in large series of biological, environmental and food samples when the elimination of macromolecules and solid particles is required.This paper will discuss how the classical limitations of dia-l ysis have been overcome to achieve a recovery of 60 to 90% of the starting analytes within 3 to 7 minutes. Analytical performances are discussed within the context of automated routine analyses using HDOC.


Traumatic peripheral nerve neurotmesis occurs frequently and functional recovery is often slow and impaired. Induced pluripotent stem cells (iPSCs) have shown much promise in recent years due to its regenerative properties similar to that of embryonic stem cells. However, the potential of iPSCs in promoting the functional recovery of a transected peripheral nerve is largely unknown. This study is the first to investigate in vivo effects of episomal iPSCs (EiPSCs) on peripheral nerve regeneration in a murine sciatic nerve transection model. Episomal iPSCs refer to iPSCs that are generated via Oct3/4-Klf4-Sox2 plasmid reprogramming instead of the conventional viral insertion techniques. It represents a relatively safer form of iPSC production without permanent transgene integration which may raise questions regarding risks of genomic mutation. A minimal number of EiPSCs were added directly to the transected nerve. Functional recovery of the EiPSC group was significantly improved compared to the negative control group when assessed via serial five-toe spread measurement and gait analysis of ankle angles. EiPSC promotion of nerve regeneration was also evident on stereographic analysis of axon density, myelin thickness, and axonal cross-sectional surface area. Most importantly, the results observed in EiPSCs are similar to that of the embryonic stem cell group. A roughly ten-fold increase in neurotrophin-3 levels was seen in EiPSCs which could have contributed to peripheral nerve regeneration and recovery. No abnormal masses or adverse effects were noted with EiPSC administration after one year of follow-up. We have hence shown that functional recovery of the transected peripheral nerve can be improved with the use of EiPSC therapy, which holds promise for the future of nerve regeneration.


Polarimetric radar measurements and products perform as the cornerstones of modern severe weather warning and nowcast systems. Two radar quantitative precipitation estimation (QPE) frameworks, one based on a radar-gauge feedback mechanism and the other based on standard rain drop size distribution (DSD)-derived rainfall retrieval relationships, are both evaluated and investigated through an extreme severe convective rainfall event that occurred on 23 June 2015 in the mountainous region over eastern China, using the first routinely operational C-band polarimetric radar in China. Complex rainstorm characteristics, as indicated by polarimetric radar observables, are also presented to account for the severe rainfall field center located in the gap between gauge stations. Our results show that (i) the improvements of the gauge-feedback-derived radar QPE estimator can be attributed to the attenuation correction technique and dynamically adjusted Z–R relationships, but it greatly relies on the gauge measurement accuracy. (ii) A DSD-derived radar QPE estimator based on the specific differential phase (KDP) performs best among all rainfall estimators, and the interaction between the mesocyclone and the windward slope of the mountainous terrain can account for its apparent overestimation. (iii) The rainstorm is mainly dominated by small-sized and moderate-sized raindrops, with the mean volume diameter being less than 2 mm, but its KDP column (KDP > 3°·km−1) has a liquid water content that is higher than 2.4815 g·m−3, and a high raindrop concentration (Nw) with log10(Nw) exceeding 5.1 mm−1m−3. In addition, small hailstones falling and melting are also found in this event, which further aggregates Nw upon the severe rainfall center in the gap between gauge stations.


Lymphocyte chromatin lability to acid hyrolysis was studied using acridine orange fluorescence metachromasia in a high-lymphocytic-leukemia-susceptibility strain (AKR) and random-bred mice (ICR). Comparisons were made of blood, thymus, and spleen lymphocytes between random-bred, "normal" AKR, and leukemic AKR animals. The leukemic mice were in the stages of the disease characterized by enlarged thymus and spleen but preceding massive elevation of blood lymphocytes. The ranges of the mean chromatin acid lability overlapped and were nearly identical in peripheral blood lymphocytes. However, thymic and splenic lymphocytes showed a marked rise in mean chromatic acid lability in the leukemic animals. The ranges of the mean values of this parameter were also found to be far greater in the lymphopoietic organs of normal AKR than in the random-bred mice. The data indicate that anatomically normal AKR animals of an age in which they are highly susceptible to spontaneous lymphocytic leukemia may contain a greater number of lymphoblasts in both the spleen and the thymus than do comparable random-bred mice. The implications of these findings are discussed in relation to strain differences and the concept of thymic origin of lymphocytic leukemia in mice.


A wave detector, a newly designed magnetic probe, is installed in the large helical device (LHD). This wave detector is a 100-turn loop coil with electrostatic shield. Comparing a one-loop coil to this detector, this detector has roughly constant power coupling in the lower frequency range of 40 MHz, and it can easily detect magnetic wave in the frequency of a few megahertz. During high-harmonic fast wave heating, lower frequency waves (<10 MHz) were observed in the LHD for the first time, and for the power density threshold of lower frequency wave excitation (7.5 MHz) the power density of excited pumped wave (38.47 MHz) was approximately -46 dBmHz. These lower frequencies are kept constant for electron density and high energy particle distribution, and these lower frequency waves seem to be ion cyclotron waves caused by nonlinear wave-particle interaction, for example, parametric decay instability.


Cooperative vehicular systems are being developed to improve traffic safety and management. Reducing road traffic congestion can be achieved through effective management strategies. In this sense, mechanisms for its rapid and accurate detection that allow evaluating the road network performance are crucial. Current Intelligent Transportation Systems (ITS) require the deployment of infrastructure sensors to monitor traffic conditions. Their installation is often expensive and their capability to provide accurate traffic information is limited. In this context, this paper proposes CoTEC (COperative Traffic congestion detECtion), a novel cooperative technique based on Vehicle-to-Vehicle (V2V) communications and fuzzy logic to detect road traffic congestion without the need to deploy infrastructure sensors. The proposed technique is also capable to accurately detect the traffic congestion intensity and length.


This paper is a comparative study of English loans in Russian and Swahili. In the twenty first century, due to the advantage of English as a global language, a language of technology and business, it has had contact with many languages of the world and has become a major source of loans to many languages. Though very different from each other, both Russian and Swahili currently have English as their main source of loanwords. This study reports the extensive adaptation of English loans by Russian and Swahili and examines how this loan items are assimilated into the two languages. It concludes that beside the adaption of pure English loans they have both employed other strategies such as loan translation, semantic extensions and loanblends for vocabulary expansion.


Ground penetrating radar (GPR) has become widely accepted as a major technique for subsurface investigations, mainly in civil engineering. Considerable efforts are put in the development of GPR systems for the detection of shallow buried landmines. However, the GPR performs inadequately due to clutter, which dominates the data and obscures the mine information. The clutter varies with surface roughness and soil conditions and lead to uncertainty in the measurements. It is therefore necessary to overcome these surrounding effects when processing GPR data for detecting small, shallow buried objects. We present improved signal processing techniques which can be used to reduce the clutter through data preprocessing. Several approaches are proposed for the GPR clutter reduction techniques, most of them model the clutter statistically. The proposed clutter reduction technique models the clutter using parametric modeling. The clutter contained in the measurements is treated as an ARMA model. The advantage of such approach lies therein that once the clutter is satisfactorily known, any target will show up as a small anomaly in against the known clutter background. This method suggests that the clutter shows a certain amount of correlation. Experimentally it is shown that the dominant interference in GPR data is correlated clutter, i.e., interference, which has a large correlation coefficient for tags greater than zero. However, the clutter environment cannot be considered completely stationary. An ideal filter would then be an adaptive filter, which estimates the slowly varying local clutter parameters, all the time ignoring the small parameter jumps caused by the buried targets to be detected. Kalman filtering is used for the estimation of the clutter parameters in the presence of random noise, detects jumps that occur at unknown points in time, and provides estimates of the new parameter values, without altering the target return.


The biological ion channel gramicidin A (gA) was modified by synthetic means to obtain the tail‐to‐tail linked asymmetric gA‐derived dimer compound 3. Single‐channel current measurements for 3 in planar lipid bilayers exhibit an Eisenman I ion selectivity for alkali cations. The structural asymmetry does not lead to an observable functional asymmetry. The structure of 3 in solution without and with Cs cations was investigated by 1H‐NMR spectroscopy. In CDCl3/CD3OH (1 : 1, v/v), 3 forms a mixture of double‐stranded β‐helices. Upon addition of excess CsCl, the double‐stranded species are converted completely into one new conformer: the right‐handed single‐stranded β‐helix. A combination of DQF‐COSY and TOCSY was used for the assignment of the 1H‐NMR spectrum of the Cs–3 complex in CDCl3/CD3OH (1 : 1, v/v). A total of 69 backbone, 27 long‐range, and 64 side‐chain distance restraints were obtained from NOESY together with 25 φ and 14 χ1 torsion angles obtained from coupling constants. These data were used as input for structure calculation with dyana built in sybyl 6.8. A final set of 11 structures with an average rmsd for the backbone of 0.45 Å was obtained (PDB: 1TKQ). The structure of the Cs–3 complex in solution is equivalent to the bioactive channel conformation in the membrane environment.


Questions: How to evaluate the mixture effect on basal area increment in two-species forest stands? Is a mixed Norway spruce–silver fir stand more productive than pure adjacent stands of either species? How to develop generic modelling approaches to assess mixture effects in forest stands?

Location: In addition to a case study on Norway spruce–silver fir stands in French mountain forests, the generic approach used goes beyond local applications.

Methods: We took advantage of National Forest Inventory data to develop a unique stand basal-area-increment model for pure and mixed stands of Norway spruce and silver fir that responds to ecological site conditions. The database was made up of 284 pure Norway spruce stands, 196 pure silver fir stands, and 323 mixed stands of these species.

Results: Pure silver fir basal area increment is strongly influenced by spring climatic conditions, whereas pure Norway spruce is more influenced by soil conditions. The mixture of these species has a positive effect on silver fir, which decreases as the proportion of fir increases. In contrast, the mixture has no noticeable effect on Norway spruce.

Conclusion: We developed a stand basal-area-increment model evidencing an advantage of the mixture on silver fir basal area increment, but not on Norway spruce. The mathematical formulation of the model developed is generic and can be used in all two-species mixture situations. It also makes it possible to compare different mixture situations with each other.


The biallelic variations of the LNPK gene are associated with the "neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum" phenotype [MIM:618090] in the Online Mendelian Inheritance In Men database, and so far, two families have been identified in the literature. A third family with novel clinical features, who bears a novel variant in LNPK (NM_030650.3: c.770delA, p.D257fs*31) is described in the present study. The coexistence of psychomotor regression and neurodegeneration in brain magnetic resonance imaging was found for the first time in the present study, thanks to the long‐term follow‐up data on the case, which contributed to the phenotypic and mutation spectrum by means of the novel variation.


As data volumes continue to rise, manual inspection is becoming increasingly untenable. In response, we present MacroBase, a data analytics engine that prioritizes end-user attention in high-volume fast data streams. MacroBase enables efficient, accurate, and modular analyses that highlight and aggregate important and unusual behavior, acting as a search engine for fast data. MacroBase is able to deliver order-of-magnitude speedups over alternatives by optimizing the combination of explanation and classification tasks and by leveraging a new reservoir sampler and heavy-hitters sketch specialized for fast data streams. As a result, MacroBase delivers accurate results at speeds of up to 2M events per second per query on a single core. The system has delivered meaningful results in production, including at a telematics company monitoring hundreds of thousands of vehicles.


Since the 21st century, noninvasive brain-computer interface (BCI) has developed rapidly, and brain-computer devices have gradually moved from the laboratory to the mass market. Among them, the TGAM (ThinkGear Asic Module) and its encapsulate algorithm have been adopted by many research teams and faculty members around the world. However, due to the limited development cost, the effectiveness of the algorithm to calculate data is not satisfactory. This paper proposes an attention optimization algorithm based on the TGAM for EEG data feedback. Considering that the data output of the TGAM encapsulate algorithm fluctuates greatly, the delay is high and the accuracy is low. The experimental results demonstrated that our algorithm can optimize EEG data, so that with the same or even lower delay and without changing the encapsulate algorithm of the module itself, it can significantly improve the performance of attention data, greatly improve the stability and accuracy of data, and achieve better results in practical applications.


The aim of this study is to provide an experimental properties evaluation of a standard filter material (cellulose) and materials with fiber layer addition with small diameters (nanofibers). Filter media, including cellulose, used in the internal combustion engine inlet air filtration are made of high diameter fibres, approx. 15 µm. Significantly higher separation and filtration efficiency performance are obtained for materials with lower fibre diameters (nanofibres), however, at the expense of a significantly higher pressure drop, affecting the engine performance. Filter media manufacturers mainly specify the structure parameters (pore size, air permeability and thickness), without giving any information on the dust filtration performance and rate. The literature includes test results for models of different filter media structures. Filtration process modelling using polydisperse dust with particles of different shape and density and irregular filter media structure is possible using advanced computer techniques, however, the process is complex and requires many simplifications. Test results can be applied directly in the automotive industry. The data can be obtained by experimental tests on filter medium specimens, complete filter elements or air filters which are costly and time-consuming tests, however, those test methods are the most reliable. Conditions and testing methodology for intake air filter materials used in internal combustion engines were developed. Filtration and flow resistance efficiency and accuracy were done depending on test dust mass stopped per unit area. Tested materials filtration efficiency was assessed by a filtration quality factor, which includes experimentally determined efficiency and accuracy as well as flow resistance values. Much higher efficiency and filtration accuracy of dust grains below 5 µm in filtration materials with nanofibers addition compared to standard filtration material (filter paper) were demonstrated. For the same flow resistance values, filter materials with nanofibers addition accumulate smaller dust mass than standard filter paper. Usage of materials with nanofibers addition used in motor vehicles intake air filtration ensures their high efficiency and accuracy. It minimises its components wear, but at the expense of faster flow resistance increase, which shortens filter life and increases filter replacement frequency. Results obtained during the experimental research partly fill the gap when it comes to the basic material properties used in internal combustion engines intake air filter partitions production.


Debris‐flow fans form by shifts of the active channel, termed avulsions. Field and experimental evidence suggest that debris‐flow avulsions may be induced by depositional lobes that locally plug a channel or superelevation of the channel bed above the surrounding fan surface, by analogy to fluvial fans. To understand debris‐flow avulsion processes, we differentiate between these controls by quantifying the spatial distribution of debris‐flow lobe and channel dimensions, along with channel‐bed superelevation, on nine debris‐flow fans in Saline Valley, California, USA. Channel beds are generally superelevated by 2–5 channel depths above the fan surface, and locally by more than 7 channel depths, thereby substantially exceeding superelevation on fluvial fans. Depositional‐lobe thickness and channel depth decrease with distance from the fan apex, although both are highly variable across the fans. Median channel depths roughly correspond to the 50th–75th percentiles of lobe thicknesses, while minimum channel depths roughly correspond to the 10th–25th percentiles. In contrast, the thicknesses of lobes that have triggered avulsions roughly equal local channel depths and are on average twice as thick as the local median lobe thickness. The spatial correspondence between avulsion locations and thick lobe deposits, and the lack of correlation with channel‐bed superelevation, leads us to infer that avulsions on these fans are mostly caused by thick lobes forming channel plugs. Although results may vary with climatic and tectonic setting, our findings indicate that avulsion hazard assessment on populated fans should include mapping and monitoring of channel depths relative to typical deposit thicknesses on a given fan.


The first case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identification was confirmed by rRNA amplification and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.


This article identifies the assumption of responsibility as a basic need of human beings and applies the concept specifically to older people with dementia or Alzheimer's disease. It suggests a two-level concept of responsibility, based on the approach of discourse ethicist Karl-Otto Apel, as a promising approach to recognizing human diversity while at the same time respecting people's equal rights to participate in discourse. This concept can serve as a theoretical starting point for the construction of individually adapted types of responsibility. Furthermore, the article describes practical ideas (primarily the practice of doll therapy) that can enable people with dementia or Alzheimer's disease to assume responsibility. Direct communication and a reflective, sensitive consideration of each individual case are identified as important prerequisites for the inclusion of elderly people with dementia.


Using the tight-binding approach we calculate the pressure-induced transition between the and (L) substitutional donor states. There are no energy barriers for such transformation and this is in agreement with the experimental findings. The arguments are presented that the DX state of this donor arises from the (L) resonant state as a result of spontaneous tetragonal distortion.


Background: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cellbiological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor. Methods: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines. Results: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer. Conclusion: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility.


AIM
to determine the number of measurements required to obtain stable bandwidth values for spatial frequency channels (SFCs) in the human visual system.

MATERIAL AND METHODS
Ten untrained, normal vision subjects 18-22 years old were presented with light pulses (flickers) with initial frequency of 10 Hz and then with a higher-than-initial and lower-than-initial frequency alternately at 1-sec intervals. The difference between flickers frequencies was gradually increased until the test subject determined his/her discrimination threshold. This threshold was assumed to represent the SFC bandwidth. Measured values were plotted on a coordinate system «SFC bandwidth - the number of measurement». The described procedure was repeated and a graph resulted showing SFC bandwidth as a function of Ni, where Ni is the number of i-th measurement and i = 1, 2, ..., k (k - the sequence number of measurement at which the transition process was completed and a quasi-stationary state achieved): ΔF=f(Ni). The number of measurements required to obtain stable SFC bandwidth values was determined from the number of measurements made during the transition process.

RESULTS
It has been found that to obtain stable bandwidth values for SFCs of the human visual system, 2 to 8 measurements are required (point estimate of the median for the given sample equaled 5).

CONCLUSION
The duration of a transition process to stable SFC bandwidth values is individual and this should be taken into account when assessing the visual system.


A simple, precise and accurate HPLC method was developed, optimized and validated for simultaneous determination of rosuvastatin and candesartan in rat plasma using atorvastatin as an internal standard. Solid-phase extraction was used for sample clean-up and its subsequent optimisation was carried out to achieve higher extraction efficiency and to eliminate matrix effect. A quality by design approach was used, wherein three-level factorial design was applied for optimisation of mobile phase composition and for assessing the effect of pH of the mobile phase using Design Expert Software. Adequate separation for both analytes was achieved with Waters C18 column (250 × 4.6 mm, 5 μm) using ACN: 5 mM Sodium acetate buffer (70:30, v/v; pH adjusted to 3.5 with acetic acid) as a mobile phase at a flow rate of 1.0 ml/min and wavelength of 254 nm. The calibration curves were linear over the concentration ranges of 5-150 ng/ml and 10-300 ng/ml for ROS and CAN respectively. The validated method was successfully applied to Pharmacokinetic study in Wistar rats and the data did not reveal any evidence for a potential drug-drug interaction between ROS and CAN. This information provides evidence for clinical rational use of ROS and CAN.


Large variations in the level and quality of NHS care in England in a range of clinical areas, including diabetes, stroke, and cancer, have been highlighted in an atlas.

The NHS Atlas of Variation shows the amount each of the 152 primary care trusts spends on various clinical services and links this with the health outcomes patients see. The results are presented in 34 geographical maps. The atlas, produced as part of the Quality, Innovation, Productivity and Prevention Programme, aims to stimulate awareness of variations that exist and help commissioners of care make better purchases.

Launching the atlas, the health minister Lord Howe said, "Making this information available to commissioners and patients will help them to identify and address unwarranted variation to better meet the needs of their local populations."

The atlas shows a sixfold variation between primary care trusts in the emergency admissions rate for asthma among under 18 year olds. Although asthma is influenced by environmental factors, even among trusts in urban London there is a more than …


A discrete-trial current-threshold self-stimulation procedure was used to assess the effects of increased and decreased serotonergic neurotransmission, and 5-HT(1A) receptor activation on brain stimulation reward. Systemic administration of the 5-HT(1A) receptor agonist 8-OH-DPAT had a biphasic effect on brain reward thresholds, without affecting the latency to respond, a measure of performance. The low dose of 8-OH-DPAT (0.03 mg/kg) lowered reward thresholds, whereas higher doses (0.1 and 0.3 mg/kg) elevated thresholds. The 5-HT(1A) receptor antagonist p-MPPI had no effect on brain stimulation behavior, but reversed both the 8-OH-DPAT-induced lowering and elevation of thresholds, indicating that both of these effects of 8-OH-DPAT are mediated through the 5-HT(1A) receptor. Injections of 8-OH-DPAT into the median raphé nucleus also lowered brain reward thresholds, without affecting measures of performance, whereas injections of 8-OH-DPAT into the dorsal raphé nucleus had no effect. A high dose of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg) elevated reward thresholds and responses latencies, whereas lower doses (2.5 and 5.0 mg/kg) increased response latencies without affecting thresholds. Furthermore, the coadministration of a 5-HT(1A) antagonist, p-MPPI, and a previously ineffective dose of fluoxetine, a drug combination that increases serotonin levels, significantly elevated thresholds. Thus, it is suggested here that the reward-potentiating effects of systemically administered low doses of 8-OH-DPAT may be the result of reduced serotonergic neurotransmission, mediated by activation of 5-HT(1A) somatodendritic autoreceptors in the median, but not the dorsal, raphé nucleus. In conclusion, the present data support the hypothesis that serotonin exerts an inhibitory influence on reward processes.


Background Behçet's disease (BD) is a multi-systemic disorder of unknown aetiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological and musculoskeletal system. Although disease pathogenesis is still unclear, the main actors seem to be genetic background and activation of both innate and adaptive immunity ensuing in an interaction between T lymphocytes and neutrophils. Indeed, multiple pro-inflammatory cytokines are involved in different pathogenic pathways that eventually lead to tissue damage in BD. Objectives The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9 and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. Methods The study included 78 serum samples obtained from 58 BD patients. We analysed a set of pro-inflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11 and CXCL9 by multiplex bead analysis as well as SAA by ELISA. Results Compared to HC, BD patients showed elevated cytokine levels of IL-8 (p=0.0001), IL-18 (p=0.0058), IFN-α2a (p=0.0181) and IL-6 (p=0.0233), and low levels of CXCL11 (p=0.0369) (Table 1). When BD patients were divided into active and inactive group, we observed enhanced IL-8 and IL-18 in both groups compared to HC, while IFN-α2a (p=0.0141) and IL-6 (p=0.0332) were raised in active group compared to HC. Moreover, CXCL11 (p=0.0154) serum concentrations were significantly lower in inactive-BD than HC (Table 1). In the second part of the study, we compared serum cytokine profiles between BD patients with SAA serum levels ≤20 mg/L (negative-SAA), >20 mg/L (positive-SAA) and HC. Interestingly, we observed that positive-SAA BD patients showed higher levels of inflammatory markers than HC or negative-SAA group. Among these cytokines, IL-18, IFN-α2a and IL-6 were higher in positive-SAA BD group than HC whilst IL-8 and CXCL9 levels were higher than in negative-SAA and HC (Table 1). Conclusions BD patients exhibited elevated levels of inflammatory mediators, more evident in active disease and positive-SAA group, suggesting that may exist a relationship between SAA and pro-inflammatory cytokines in the intricate scenario of BD pathogenesis. References Hatemi G, Yazici Y, Yazici H. Behçet's syndrome. Rheum Dis Clin North Am 2013; 39:245–61. Hamzaoui K, Hamzaoui M, Guemira F, Bessioud M, Hamza M & Ayed K. (2002) Cytokine profile in Behcet's disease patients. Relationship with disease activity. Scand J Rheumatol 31: 205-10. Uhlar CM, Whitehead AS. Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem. 1999 Oct;265(2):501-23. Nara K, Kurokawa MS, Chiba S et al. Involvement of innate immunity in the pathogenesis of intestinal Behcet's disease. Clin Exp Immunol 2008;152:24551. Disclosure of Interest None declared


Objective – This paper offers a review of the latest studies with regards to the impact of COVID-19 on small
businesses in different countries around the world.
Methodology – This paper reviewed a compilation of COVID-19 studies focusing on SMEs that was conducted
between 2020 and 2022. The review enables us to understand the globally common or underlying challenges to SMEs
due to COVID-19, along with an assessment of government's initiatives that were implemented to alleviate the impact.
The review revealed that the pandemic caused a major disruption for small businesses which also acts as a catalyst
towards digitization and innovation towards competitiveness which is facilitated by government initiatives. The review
process comprises systematic and vast-ranging search for articles related to the subjects to look for evidence, and
secondly, for limit the risk of biasness.
Findings – This survey of experiences elsewhere might provide insights to policymakers in countries that are struggling
to cope with the problem on the initiatives to consider and the additional initiatives that might be necessary to make
them effective in their individual country contexts.
Novelty – Given limitations of space, we survey only a limited sample of countries from Asia and Europe, along with
the US and Canada. Hopefully, their experiences will provide a broad enough spectrum of initiatives for policymakers
elsewhere to consider and evaluate.
Type of Paper: Review
JEL Classification: M21, O38


This study is aimed to evaluate the health related quality of life (HRQL) in asthmatics and the probable association between HRQL and disease severity and also other demographic factors by using a generic scale, SF-36 questionnaire. One-hundred and two asthmatics were enrolled. The scores of the 8 domains of SF-36 questionnaire were evaluated according to age, gender, status of education and compared with the severity of asthma. The mean age of 84 (83%) female and 18 (17%) male patients was 42.86 +/- 11.15. Fifty-two of them was well educated (51%) and 50 was poorly educated (49%). Atopy ratio was 81%. Mild intermittent, mild persistent and moderate-severe persistent groups were 27 (26%), 46 (45%) and 29 (29%) respectively. Female gender were worse in physical functioning (p= 0.000), physical role difficulties (p= 0.0049), vitality (p= 0.045) and social functioning (p= 0.025). Poorly educated group were worse in physical functioning (p= 0.001), physical role difficulties (p= 0.039), vitality (p= 0.045), emotional role difficulties (p= 0.046), general health (p= 0.030) and mental health (p= 0.044). Mental health was worse in the presence of atopy (p= .035). Physical functioning was better in mild intermittent group than moderate and severe persistent group (p= 0.024). General health was better in mild intermittent group than mild persistent group (p= 0.018), moderate and severe persistent group (p= 0.015). Vitality and emotional role difficulties was better in mild intermittent than mild persistent group (p= 0.042, p= 0.007). The HRQL scores and severity of asthma is well correlated like other objective parameters. So one of the primary goals in management of asthma should also improve QOL as well as functional parameters.


It remains unclear whether the combination of dual‐chamber (DDD) pacing and disopyramide can achieve prolonged left ventricular outflow tract (LVOT) gradient reduction and symptom relief in patients with obstructive hypertrophic cardiomyopathy (HCM). In an HCM patient with a severe LVOT gradient, the combination of DDD pacing and disopyramide achieved marked improvement of gradient in the catheter laboratory and also after medium‐term follow‐up. The patient's severe dyspnoea was alleviated during the follow‐up period. This combination might enable physicians to treat and manage elderly symptomatic obstructive HCM patients with a severe LVOT gradient more effectively and less invasively.


The effects of various equilibrium time,temperature and pH on the adsorption of Ge(Ⅳ) on nano-Al2O3 were studied. The results show that the adsorption is fast to reach equilibrium within 2 min. It was found that the adsorption efficiency of Ge(Ⅳ) was more than 95% with pH from 4 to 11. Almost all of Ge(Ⅳ) ions adsorpted onto nano-Al2O3 can be eluted with 0.3 mol/L K3PO4-1 mol/L H2SO4 mixed solution within 5 min,the desorption percentage can reach 97%. The sorption of Ge(Ⅳ) ions onto nano-Al2O3 followed the second-order rate equation,the kinetic experimental data properly correlate with the second-order kinetic model and the values of activation energy(Ea) was 11.63 kJ/mol. The adsorption data are fitted to the Freundlich and the magnitude of sorption energy computed from D-R equation is 10.87 kJ/mol,thus,the type of the adsorption of germanium on nano-Al2O3 is a chemical adsorption. The ΔG0 and ΔH0 values is negative and positive respectively which indicate the adsorption of Ge(Ⅳ) on nano-Al2O3 is spontaneous and endothermic.


The paper discusses the development and impact of construction research the past 25 years. Theoretically, the paper builds on two fundamental insights: The Pareto principle (the 80-20 rule) and the Thomas theorem: "If men define situations as real, they are real in their consequences" (Thomas and Thomas 1928: 572) a fundamental sociological principle. The Pareto principle is applied using the concept "The long tail" (Anderson 2006). Based on "the long tail" the three different production paradigms of mass production, mass customisation, and individual customisation are identified. The paper argues that construction in the 1950s and 1960s was driven by a "mass production" paradigm that from the beginning of the 1980s was replaced by an "individual customisation" paradigm in which construction became a matter of tailoring unique buildings to each customer. These two different paradigms have been driven by two more or less unarticulated myths. In the 1960s buildings were viewed as standardised while they from the 1980s onwards have been viewed as unique. Based on the Thomas theorem it is argued that these myths have had a substantial impact on the way we build. Consequently, today"s predominant view of buildings – as unique – implies that: 1) the nature of the construction processes is chaotic, 2) the buildings are realised through onsite project work rather than through offsite production; and 3) project management is the fundamental management principle. The paper further identifies how attempts to develop new construction practices like partnering and lean implicitly reproduce this myth. The result is that construction research the past 25 years has been constructing the long tail in a way that hinders radical development of the construction industry. The paper concludes that if we allow ourselves to view buildings as both unique but also as standardised we can create a new platform for developing the construction industry – a Mass Customisation paradigm.


Abstract Aim: The aim of this study is to investigate the accuracy of dose distributions calculated by the BrachyDose Monte Carlo (MC) code in heterogeneous media for high-dose-rate (HDR) brachytherapy and to evaluate its usability in the clinical brachytherapy treatment planning systems. Materials and methods: For dose comparisons, three different dose calculation algorithms were used in this study. Namely, BrachyDose MC code, Eclipse TG-43 dose calculation tool and Acuros®BV model-based dose calculation algorithm (MBDCA). Dose distributions were obtained using any of the above codes in various scenarios including 'homogenous water medium scenario', an 'extreme case heterogeneous media scenario' and clinically important 'a patient with a cervical cancer scenario'. In the 'extreme case, heterogeneous media scenario', geometry is a rare combination of unusual high-density and low-density materials and it is chosen to provide a test environment for the propagation of photons in the interface of two materials with different absorption and scattering properties. GammaMed 192Ir Model 12i Source is used as the HDR brachytherapy source in this study. Dose calculations were performed for the cases where there is either a single source or five sources planted into the phantom geometry in all homogenous water phantom and extreme case heterogeneous media scenarios. For the scenario a patient with a cervical cancer, dose calculations were performed in a voxelized rectilinear phantom, which is constructed from a series of computed tomography (CT) slices of a patient, which are obtained from a CT device. Results: In homogeneous water phantom scenario, we observed no statistically significant dose differences among the dose distributions calculated by any of the three algorithms at almost every point in the geometry. In the extreme case heterogeneous media scenario, the dose calculation engines Acuros®BV and BrachyDose are agreed well within statistics in every region of the geometry and even in the points close to the interfaces of low-density and high-density materials. On the other hand, the dose values calculated by these two codes are significantly different from those calculated by the TG-43 algorithm. In the 'a patient with a cervical cancer scenario', the calculated D2cc dose difference between Acuros®BV and BrachyDose codes is within 2% in the rectum and 11% for the bladder and sigmoid. There was no meaningful difference in the mean dose values between MBDCAs in the bone structures. Conclusions: In this study, the accurate dose calculation capabilities of the BrachyDose program in HDR brachytherapy were investigated on various scenarios and, as a MC dose calculation tool, its effectiveness in HDR brachytherapy was demonstrated by comparative dose analysis.


This thesis presents a multidisciplinary, mixed methods approach that combines Film Studies and Human Computer Interaction (HCI), aiming to elucidate the rapidly digitised cinema-going experience and its implications on the construction of cinema audiences' digital identity. Existing literature in the field of Film Studies has looked into it from a social, economic and architectural perspective, without taking into consideration the emerging incorporation of digital practices and therefore, digital footprint within the cinema-going experience itself. HCI scholars have experimented with enriching the cinema-going experience using technological interventions but their research remains limited in the screening room space. Combining Film Studies and HCI, this research project suggests a new insight on audience research.

The conducted fieldwork consists of focus groups, expert interviews, participatory design, diaries, prototyping and prototype evaluation workshops. The studies' results reveal that cinema-going is a holistic experience, a trajectory that begins before reaching the cinema, during one's presence in it and after walking away from it, consisting of multiple physical and digital interactions, activities, platforms and devices that leave behind digital traces. Mapping this journey led to the segmentation of cinemagoers in four different types according to their cinema-going related behaviours. The approach followed resulted in the development of a prototype of a multiplatform system that provides enhanced and personalised experiences, made by the users for the users, taking into account what they think as important, beneficial, and problematic.

This PhD project contributes to the field of Film Studies using an HCI methodological approach to renew cinema history literature, adding an understanding of how audiences make use of digital platforms and data during the contemporary cinema going experience. Additionally, it adds a contextual contribution to the HCI community, extending user needs and data handling in the field of cinema by presenting cinema-going trajectories in the digital age. The exploration of digital identity construction within cinema-going extends the digital identity literature of both fields by examining the actual audiences' practices and viewpoint but also by getting the cinema exhibition's perspective on the matter. Finally, implications for design serve as a basis for expanding on the suggested prototypes and designing better cinematic experiences that address users' needs –adding to the list a commercial contribution of the project.


Spatial patterns of logistics industry is formed by the spatial distribution and structure of logistics facilities and enterprises. In order to examine the current situation and change of spatial patterns of logistics industry in China, we put forward the concepts of "logistics hotness degree " and "primacy index of cities." In August 2014, we obtained 80507 samples of logistics hotness degree data at the prefecture level or above in China based on "logistics" key word search using Baidu maps(excluding Hong Kong, Macao, and Taiwan).Through establishing an index of logistics hotness degree, the correlation between logistics hotness degree and indicators were analyzed. This article presents the construction of the logistics hotness degree index and demonstrates the effectiveness and validity of Internet- based data on logistics industry. Spatial patterns of logistics industry are analyzed in terms of capacity, level of service, and spatial influence at the prefecture,provincial, metropolitan area, and economic zone scales. We explored the impact of economic development and logistics park construction on the evolution of the spatial patterns of logistics industry. Logistics centers were identified and compared to the national and regional logistics hub cities designated in the "Logistics Industry Restructuring and Revitalization Plan" issued by the State Council and the "National Logistics Park Development Planning" issued by the National Development and Reform Commission and 11 other ministries.Some conclusions can be drawn as follows: the logistics hotness degree information is a comprehensive representation of logistics facilities and logistics enterprises.It is highly correlated with GDP, number of primary industry corporation units in transportation, warehousing, and postal services. Economic development level is highly correlated with logistics industry development. The spatial layout of logistics facilities and enterprises is significant correlated with industrial demand and their locations in the transport system; and it increasingly influenced by the of consumption demand and distribution and socioeconomic conditions of population. In the eastern coastal region of China, logistics industry distribution shows the spatial characteristics of "single-center and multiple sub- centers" or "multiple- centers and multiple sub- centers." In the central and western regions,however, the spatial pattern of distribution is characterized by "single- centers," which shows a clear regional difference from the coastal region. The result of this research may provide some guidance for logistics plann ing and logistics industrial policy of the central and regional governments for the thirteenth Five- Year Plan period and beyond.


The Authors, when presenting a personal case of CBL, make a critical revision of the literature, summing up the evolution of knowledge of this morbid picture. They analyse and discuss the aetiological theories suggested by other Authors on the basis of clinical and anatomopathological criteria. Lastly they evidence the difficulty of diagnosis both for the clinical physician and for the anatomopathologist, since there are numerous pathological pictures which may simulate CBL in the symptoms when present, the x-ray aspects and even the anatomohistological examination.


Weblogs are gaining popularity across the global digital community. They provide opportunities for individuals to engage in argumentation and express views as well as disseminate information or discuss issues. This research investigates the linguistic features of argumentation in selected Malaysian social- political weblogs based on the discourse analysis of six weblog posts written by two Malaysian social-political (sopo) bloggers on social themes. This comparative analysis was facilitated by a comprehensive pragma-dialectic model of argumentation as well as a critical discussion of the impact of socio-cultural factors on argumentation contained in the selected Malaysian blogs. The study also offers useful insights into the ways in which standpoints are expressed in argumentations in different cultural contexts. Awareness of the salient features of cultural argumentation would enable blogs to be better understood by a wider audience from other cultures, and ultimately reaching a more global readership


Most art paintings especially abstract art are created to evoke an emotional feeling in the viewer. Colour as a dominant low-level feature plays a significant role in visual perception. Colours can bring out different emotional feelings and the findings from several psychology studies have shown bright colours generally relate to positive emotions, whereas dark colours relate to negative emotions. This paper focuses on the study of relationships between colours and emotionson abstract art images. In this work, the colour featurevectors were extracted from images using the fuzzy colour histogram method, whereas emotion typevectors were obtained from a user rating study done on an abstract art imagedataset. Ourstudy shows that some emotion types have highly significant association with certain colours. For example, the fear emotion has a positive correlation with the colour black with a significant value of p <; 0.01.


Introduction Part I. Concepts of National Identity and the Symbolic Construction of Nations: 1. National identity and the conditions of tolerance 2. The historical invention and modern reinvention of two national identities 3. Segmented politics: xenophobia, citizenship, and political loyalty in Germany 4. The discoursive construction of national stereotypes: collective imagination and racist concepts in Germany before World War I 5. Integration and fragmentation discourses: demanding and supplying 'identity' in diverse societies Part II. The Social and Cultural Practice of Racism: 6. Race, class, and Southern racial violence 7. Racism and Empire: a perspective on a new era of American history 8. Police, African Americans, and Irish immigrants in the nation's capital 9. The politics of boycotting: experiences in Germany and the United States since 1880 10. Jews and the German language Part III. Race, Gender, Body, Biology: 11. Ambiguous roles: the racial factor in American womanhood 12. Citizenship embodied: racialized gender and the construction of nationhood in the United States 13. Body matters: race, gender, and perceptions of physical ability from Goethe to Weininger 14. A horse breeder's perspective: scientific racism in Germany, 1870-1933 15. The thin line between eugenics and preventive medicine.


The structure optimization and frequency calculation of hexaazatriphenylene, triphenylene and their derivatives were carried out at the level of B3LYP/6-31G ** , and the most stable configurations were obtained. On the basis of the most stable geometries, the relationships of the total energy with rotation degrees between the dimers were studied, and the lowest energy point was obtained. Based on the semi-classical model of the charge transport, our results predict that hexaazatriphenylene molecules have the largest positive charge transport rate and the smallest negative charge transport rate. Introduction of SH, OH, O R and F groups make the positive charge transport to increase, and the negative charge transport to decrease. The length of alkoxy group has little effect on charge transport properties.


Stanford SOLAR Centre of Stanford University introduced the Space Weather Monitoring program with the aim of building and distributing inexpensive ionospheric monitors named Sudden Ionospheric Disturbance or SID for short. These SIDs are used to detect changes to the Earth's ionosphere caused by solar flares and other ionospheric disturbances. In 2009, through collaboration between the Institute of Space Science (ANGKASA), UKM (currently known as Space Science Centre) and Stanford University, U.S., research in remote sensing using Very Low Frequency (VLF) receiver was initiated at UKM using the AWESOME monitor. Later, when the International Space Weather Initiative (ISWI) was established with the main aim of focusing on space weather research, UKM was provided with a set of low cost version of the AWESOME monitor called Super Sudden Ionospheric Disturbance (SuperSID) ionospheric monitor which was designed for high school. In 2012, UKM researchers succeeded in building their own VLF receiver system known as UKM-SID. The UKM-SID system that include a teaching module was developed for the SID Introductory Project aimed to promote awareness and better understanding of space weather among high school students in Malaysia, in addition to cultivating students' interest in research through hands-on activities and usage of the UKM-SID ionospheric monitor.


In a magneto-optic head with differential detection, the light level on the data detectors is determined by the ratio of a semi-polarizing beam splitter. This paper presents a way of measuring the various noise sources with a common set of values and uses this data to choose the beam splitter ratio that optimizes the SNR.


The modern study of astrophysical transients has been transformed by an exponentially growing volume of data. Within the last decade, the transient discovery rate has increased by a factor of ∼20, with associated survey data, archival data, and metadata also increasing with the number of discoveries. To manage the data at this increased rate, we require new tools. Here we present YSE-PZ, a transient survey management platform that ingests multiple live streams of transient discovery alerts, identifies the host galaxies of those transients, downloads coincident archival data, and retrieves photometry and spectra from ongoing surveys. YSE-PZ also presents a user with a range of tools to make and support timely and informed transient follow-up decisions. Those subsequent observations enhance transient science and can reveal physics only accessible with rapid follow-up observations. Rather than automating out human interaction, YSE-PZ focuses on accelerating and enhancing human decision making, a role we describe as empowering the human-in-the-loop. Finally, YSE-PZ is built to be flexibly used and deployed; YSE-PZ can support multiple, simultaneous, and independent transient collaborations through group-level data permissions, allowing a user to view the data associated with the union of all groups in which they are a member. YSE-PZ can be used as a local instance installed via Docker or deployed as a service hosted in the cloud. We provide YSE-PZ as an open-source tool for the community.


The primary regulation of cardiac contractility is probably through changes in the level of cytoplasmic free Ca $^{2+}$ . In the stimulation of contraction by catecholamines, secondary controls may be present at the level of the contractile proteins. Troponin-I, a subunit of the troponin complex of the thin filament, and C-protein, a thick filament component, are both phosphorylated in perfused hearts in response to catecholamines over time courses similar to that for the increase in contraction. Both proteins are also phosphorylated rapidly in vitro by cyclic-AMP-dependent protein kinase. Phosphorylation of troponin-I causes a decrease in the sensitivity of both cardiac myofibrillar ATPase and tension development of skinned fibre preparations to Ca $^{2+}$ , and also an increase in the rate of dissociation of Ca $^{2+}$ from isolated troponin. These results support the hypothesis that the role of phosphorylation of cardiac troponin-I is to contribute to the increased rate of relaxation of the heart that is observed with catecholamines. C-protein is phosphorylated to a maximum of 4-5 mol phosphate per mole protein both in vivo and in vitro. At present, however, the functions of both C-protein itself and its phosphorylation arc unknown. Dephosphorylation of these contractile proteins after catecholamine stimulation is slow in perfused heart, although the rate can be increased by cholinergic agents. Phosphorylase, in contrast, is rapidly dephosphorylated under these circumstances. Phosphoprotein phosphatases relatively specific for phosphorylase have been identified in rat heart, whereas troponin-I appears to be dephosphorylated by general phosphatases. These observations account for the different rates of dephosphorylation of phosphorylase and the contractile proteins, but do not explain the slow dephosphorylation of the latter. In control perfused hearts myosin P-light chain was 50% phosphorylated, and this was not changed by perfusion with positive inotropic agents or by short-term ischaemia. It was also unchanged during long-term hormonal modifications. Perfusions with $^{32}$ P $_i$ in rat heart give a half-time for the turnover of phosphate bound to the P-light chain of 2-4 min, showing that the myosin light chain kinase and phosphatase are active in the heart. It is hypothesized that under control conditions the kinase is already fully active, and that an increase in cytoplasmic Ca $^{2+}$ cannot therefore cause further activation of the enzyme.


The DOE Division of Waste Products through a lead office at Savannah River is developing a program to immobilize all US high-level nuclear waste for terminal disposal. DOE high-level wastes include those at the Hanford Plant, the Idaho Chemical Processing Plant, and the Savannah River Plant. Commercial high-level wastes, for which DOE is also developing immobilization technology, include those at the Nuclear Fuel Services Plant and any future commercial fuels reprocessing plants. The first immobilization plant is to be the Defense Waste Processing Facility at Savannah River, scheduled for 1983 project submission to Congress and 1989 operation. Waste forms are still being selected for this plant. Borosilicate glass is currently the reference form, but alternate candidates include concretes, calcines, other glasses, ceramics, and matrix forms.


Abstract Three hundred and sixty Hubbard broiler eggs were divided into two equal groups. In the first group, eggs were incubated at 37.5 °C for up to 19 d, while those in the second group were incubated at the same temperature except for 3 d (days 6, 7, and 8) when they were exposed to 40.0 °C for 3 h each day. Eggs were equally classified into three ascorbic acid (AA) treatments. The first one was sprayed with distilled water (control), while the second and third treatments were sprayed with same solution but containing 20 and 30 g AA L-1, respectively. The highest embryo weight (EW) per gram and lowest yolk sac weight (YSW) per gram were obtained in the chronic group (P ≤ 0.05). Embryonic mortalities were significantly (P ≤ 0.05) increased, while hatchability was significantly decreased in the chronic group compared with the control group. Chick weight (g) and glucose and triiodothyronine (T3) levels were significantly lower (P ≤ 0.05) in the chronic group compared with the control group. The heterophil–lymphocyte (H/L) ratio was significantly (P ≤ 0.01) affected by incubation temperature. Body weight (g) and percentages of liver, spleen, and bursa of Fabricius were significantly (P ≤ 0.05) lower in broilers in the chronic group compared with the control group. Referring to AA treatment, EWs (g) were not affected, whereas YSW per gram, packed cell volume (PCV) (%), red blood cells (RBCs) (106), H/L ratio, and bursa percentage were significantly (P ≤ 0.05) affected.


The discipline of human factors and ergonomics is largely focused on principled development of generalizable solutions. The process is typically slow, spanning months, even years. A crisis such as the COVID-19 pandemic presents a different problem. How can human factors and ergonomics professionals react quickly, within hours or days, to provide viable solutions to unanticipated problems as they become apparent? Here we report on a small project in which we were able to respond rapidly to an emergent COVID-19 requirement. Given time constraints, we had no opportunity to follow a systematic analysis and design strategy. Our development and testing strategies reveal lessons that can be applied more generally to development of human factors and ergonomics interventions within emerging crises.


Although nonsteroidal anti-inflammatory drugs (NSAIDs) are used as cancer chemopreventative agents, their mechanism is unclear because NSAIDs have cyclooxygenase-independent actions. We investigated an alternative target for NSAIDs, peroxisome proliferator-activated receptor-γ (PPARγ), activation of which decreases cancer cell proliferation. NSAIDs have been shown to activate this receptor, but only at high concentrations. Here, we have examined binding of diclofenac to PPARγ using a cis-parinaric acid displacement assay and studied the effect of diclofenac effect on PPARγ trans-activation in a COS-1 cell reporter assay. Unexpectedly, diclofenac bound PPARγ at therapeutic concentrations (Ki = 700 nM) but induced only 2-fold activation of PPARγ at a concentration of 25 μM and antagonized PPARγ trans-activation by rosiglitazone. This antagonism was overcome with increasing rosiglitazone concentrations, indicating that diclofenac is a partial agonist. No effect of diclofenac was seen without exogenous receptor, confirming that it was working through a PPARγ-specific mechanism. This is the first description of an NSAID that can antagonize PPARγ. In addition, this is the first time that an NSAID has been shown to bind this receptor at clinically meaningful concentrations. The physiological relevance of these findings was tested using adipocyte differentiation and cancer cell proliferation assays. Diclofenac decreased PPARγ-mediated adipose cell differentiation by 60% and inhibited the action of rosiglitazone on the prostate cancer cell line, DU-145, allowing a 3-fold increase in proliferation. This work shows that standard doses of diclofenac may have pharmacodynamic interactions with rosiglitazone and this has therapeutic implications, both in the management of type 2 diabetes and during cancer treatment.


Difficult tracheal intubation (DI) is more common in thyroid than in other surgical branches due to thyromegaly. Proper preoperative airway evaluation is necessary in order to reduce the potential numerous complications. The study examined the incidence of DI in thyroid surgery and the influence of tracheal dislocation and other risk factors on DI. A prospective study was conducted on 2379 patients who underwent thyroidectomy at the Center for Endocrine Surgery, Clinical Center of Serbia, from 2007 to 2012. Patients were divided into groups with (n = 162) and without DI (n = 2217). Besides tracheal dislocation, another 13 risk factors contained in 13 screening tests and three additional factors of gender, age and diagnosis were defined. The incidence of DI in our study was 6.81%. The presence of tracheal dislocation was statistically significant, but not an independent predictor of DI. The diagnosis, large circumference and small neck length, previous DI, recessive mandible, tooth characteristics and oral anomalies were the most significant and independent predictors of DI. Neck circumference and small neck length had highest sensitivity. Previous DI had highest specificity. Thyromegaly, if causing tracheal dislocation and/or stenosis, represents a significant DI predictor, not individually, but in combination with other factors.


Studies in Spermatogenesis is a two volume book written by Nettie Maria Stevens, and published by the Carnegie Institution of Washington [3] in 1905 and 1906. In the books Stevens explains the research she conducted on chromosomal sex determination [4] in the sperm [5] and egg [6] cells of insect species while at Bryn Mawr College [7], near Philadelphia, Pennsylvania. Studies in Spermatogenesis described early examples of chromosomal XY sex-determination [8].


Due to their pathogenic potential, identifying Vibrio species from recirculating aquaculture systems (RAS) for Pacific white shrimp (Litopenaeus vannamei) is of great importance to determine the risk for animal's as well as for the consumer's health. The present study compared identification results for a total of 93 Vibrio isolates, including type strains and isolates from shrimp aquaculture. Results from biochemical identifications, 16S rRNA sequencing, sequencing of the uridylate kinase encoding gene pyrH and analysis of the protein spectra assessed by MALDI-TOF MS were compared. The results achieved by these different methods were highly divergent for many of the analysed isolates and for several Vibrio spp difficulties in reliably identifying occurred. These difficulties mainly resulted from missing entries in digital databases, a low number of comparable isolates analysed so far, and high interspecific similarities of biochemical traits and nucleotide sequences between the closely related Vibrio species. Due to the presented data, it can be concluded that for identifying Vibrio spp. from samples in routine diagnostics, it is recommended to use MALDI-TOF MS analysis for a quick and reliable identification of pathogenic Vibrio sp. Nevertheless, editing the database, containing the main spectra of Vibrio is recommended to achieve reliable identification results.


We report the synthesis of three optical probes (Eu(3+)⊂1, Eu(3+)⊂2, and Eu(3+)⊂3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)⊂1 and Eu(3+)⊂2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)⊂2 > Eu(3+)⊂1 > Eu(3+)⊂3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)⊂2 and FA or Eu(3+)⊂2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)⊂2 shows high selectivity and specificity for FR.


The thesis aims at exploring if mean-performance in the school affects individuals' probability of completion of upper secondary schooling.The aim is placed within a framework of developments within the institutional structure showing increased between-school variance in performance and the literature on contextual effects. Two opposing mechanisms are proposed on how mean- performance may affect the individual likelihood to stay in school; students may be 'influenced' by each other if increased mean-performance inspires them to more high- aspiring goals, but they can also 'compare' their performance to others' and judge their own performance as worse the higher the mean-performance of others.The population consists of all students who began an academic program in a public school in Stockholm 1998-2001. In 2000, selection procedures changed from neighborhood assignment to open-enrolment, making it possible to distinguish compositional effects from peer-effects. Register data allows for robust measures of main-variables and potential confounders. Analyses are conducted using school-fixed effect linear probability models (LPM).Firstly, there is a non-linear association between own-GPA and probability of completion; changes in own-GPA are more important for completion at low-levels of GPA. Secondly, there is an overall, albeit modest, negative effect of school level mean- GPA on the probability of completion. Thirdly, this negative effect is most pronounced among low-performing students. Thus, the results suggest that low-performers are less likely to complete when they have high-performing peers.


Representative case reports of children subjected to ureteroplasty in the management of reflux have been presented. Five- to 12-year follow-up studies were analyzed with reference to renal growth and pyelonephritic changes; the effect of the degree of preoperative reflux was recorded. The following conclusions appear warranted: 1. Severity of reflux is a major factor determining renal status; the more marked the reflux, the greater the frequency and extent of CPN. 2. Kidneys which appear normal initially usually remain so;however, CPN may develop, sometimes to a severe degree (Fig. 9). 3. The growth potential of pyelonephritic kidneys is quite variable and not readily predictable (Fig. 9). 4. Prolonged exposure to reflux appears to be an unfavourable situation possibly accelerating renal deterioration.


: 4C skills are very much needed in the 21st century and the era of the industrial revolution 4.0. The 21st century is marked by the era of the industrial revolution 4.0 as the century of openness or the century of globalization. The demands of the times require students to have soft and hard skills. Mastery of hard skills and soft skillscan be realized through the integration of entrepreneurial character and science process skills (KPS) in learning. Entrepreneurial character is the character of an entrepreneur who is implemented in the entrepreneurial process. Meanwhile, science process skills are intellectual skills to acquire, develop and apply scientific concepts, principles, laws and theories, both in the form of mental skills, physical skills and social skills. Efforts to improve the soft skills and hard skills of students can be done through various methods, one of which is through Problem Based Learning (PBL). Through the PBL model, students are guided to construct their own knowledge so that learning becomes more meaningful. Teachers are expected to be able to train and integrate entrepreneurial character and science process skills. Bioentrepreneurship is a contextual biology learning approach that links the material being studied with objects or natural phenomena that exist around the lives of students. Thus, in addition to obtaining subject matter, students also have the opportunity to learn the process of processing a material into a product that is useful, has economic value and fosters interest in entrepreneurship. Through the integration of Problem Based Learning based on Bioentrepreneurship, it is hoped that it can improve the entrepreneurial character and science process skills. So as to encourage the growth of new innovators and entrepreneurs to improve student learning outcomes and science process skills.


Regulation of protein expression in cellular level are so challenging. In cellular scale, biochemical processes are intrinsically noisy and many convenient controllers aren't physically implementable. This paper deals with the design of implementable controller for stochastic gene regulatory networks with multiplicative and additive noises. In particular, we consider structural limitations that are present in real cellular systems and design the decentralized feedback that guarantees noise to state stability. To do this end, we consider standard Lyapunov function and by using Ito formula and stochastic analysis, we derive sufficient conditions for noise to state stability presented in the form of matrix inequalities. In the next step, by defining appropriate change of variables, matrix inequalities are transformed to Linear matrix inequalities which can be used to synthesize controller with the desired structure. Since the proposed conditions for controller design are in the form of linear matrix inequalities, controller gains can be derived efficiently through solving presented LMIs numerically. It is noteworthy that Because of its simple structure, the proposed controller can be implemented universally in many cells. Finally, we consider a synthetic gene regulatory network and investigate the effectiveness of the proposed controller by simulations.


Background Clinical pathway (CP) is an application of rational process and time management for specific disease and surgery in practice. The CP was firstly introduced into China in 1990s. Objective To find the current status of clinical pathways in China. Methods We used word clinical pathway in title by searching the web of clinical pathway (www.ch-cp.org.cn), CNKI, etc. and collected CP on title, date, specialties and main contents, etc. Search date till July 30, 2012. Results 1) 331 CPs were issued in 2009-2011, 25,503 departments from 3,467 hospitals conducted CP and public hospital accounted for 46.9% by 2011 in China. 2) The CPs was pilot implemented in 110 selected hospitals from 23 provinces on 22 specialties, such as general surgery, cardiovascular, orthopaedics, etc. 3) The contents of CP mainly include: disease and target population, diagnosis, treatment option, standard length of stay in hospital, criteria for CP entrance, preoperative evaluation, time and choice for use of prophylactic antibiotics, operation day, postoperative hospital stay recovery, discharge standard, variance and reason analysis, etc. Few CP described the sources of funding, composition of group that authored the CP and financial disclosures. 4) The major influential factors of CP implementation include: the participation of doctors and patients, explanation of the various process and documents, payment problems, hospital management, appropriate incentive mechanisms, information systems and other support policies, etc. Conclusions Clinical pathway may a tool for hospital quality management and assessment criteria of disease effectiveness-costs. More communications with doctors and patients and innovative payment methods would be better for CP implementation.


This is a history of the Scandinavian critical reception of Henry James. Lilliedahl supplies a spectrum of James criticism from Sweden, Finland, Norway and Denmark from the first notices of James in this these countries down to the 1980s. She also provides a summary of the argument of each piece.


Subjective cognitive decline (SCD) is characterized by self-experienced deficits in cognitive capacity with normal performance in objective cognitive tests. While, the previous structural co-variance researches showed particularly insights into understanding the structural alterations of brain in neurodegenerative diseases. However, the age-related variations in coordinated topological patterns of morphological networks in individuals with SCD remain poorly understood. In this study, 77 individual morphological networks were constructed including 42 normal controls (NC) and 35 SCD individuals from structural Magnetic Resonance Imaging (sMRI). A stepwise linear regression model was constructed to evaluate the differences of age-related alternation patterns of the network properties in individuals with SCD compared with NC. Compared with NC, the properties of integration and segregation in individuals with SCD were lower, and the aberrant metrics were negatively correlated with age in SCD, while not in NC. The connections of rich-club were persevered but the connections of paralimbic system were disrupted in SCD compared with NC. In addition, age-related differences of nodal global efficiency mainly distributed in prefrontal cortex regions. In conclusion, the age-related disruption of topological patterns in SCD provide evidence that SCD population are at high risk to cognitive decline further.


The purpose of this study is to examine the prevalence of metabolic syndrome in nicotine treated male and female mice and to evaluate gender related differences. For these purposes adult male and female BALB/C mice were subjected to chronic nicotine treatment (3.08mg/100ml in drinking water) for 4 weeks. Serum glucose, albumin, corticosterone and lipid profile levels were determined. Body weight changes were also monitored. We have found that nicotine treatment raises total cholesterol and glucose levels more in male as compared to female mice. Low density lipoprotein cholesterol (LDL-C) levels were increased by 35% (P<0.01) only in male mice. However rise in triglycerides were greater in females (28%) than males (21%) when compared with their respective controls. Serum albumin levels were increased in both sexes showing 13% greater increase in males as compared to females. However nicotine treatment had no effect on high density lipoprotein cholesterol, corticosterone levels and body weights in both genders. It is concluded that nicotine use is positively associated with LDL-C in males; the results are discussed in relation to prevalence of metabolic syndrome and risk of cardiovascular events in nicotine users.


Leber's hereditary optic neuropathy is a maternally inherited disease associated with the late onset of bilateral loss of central vision and cardiac dysrhythmias. The maternal inheritance is explained by the mitochondrial origin of the disease. Analysis of the sequence of a mitochondrial DNA has indicated that a single nucleotide change at position 11778 is associated with this disease. This mutation converts the 340th amino acid of NADH dehydrogenase subunit 4 from an arginine to a histidine and eliminates an SfaNI endonuclease restriction site. A survey of restriction-fragment-length polymorphisms in the mitochondrial DNA of three independent families with this disease (an American black and two white European families) and 10 controls confirmed that this SfaNI site is associated with the disease. A phylogenetic tree for mitochondrial DNA polymorphism and sequence variants from three probands with Leber's disease and four controls was constructed, and the mutation at position 11778 was found to be associated with two mitochondrial DNA backgrounds--an American black mitochondrial DNA and a European mitochondrial DNA. Thus, this mutation must have arisen twice independently. Since the mutation correlated with symptoms of Leber's disease in both cases, these findings indicate that the mutation is a cause of the disease. This genetic analysis has identified the specific point mutation in the mitochondrial DNA that results in Leber's hereditary optic neuropathy.


A major purpose of this study is to develop high modulus asphalt mixtures for perpetual asphalt pavements which can save maintenance cost by increasing the design and performance periods of the pavements. Various physical and mechanical laboratory tests are performed for the high modulus asphalt binder developed in this study. The test results show that the properties of the high modulus binder are similar to those of the French high modulus binders. In addition to the binder tests, various performance tests are conducted for the high modulus and conventional mixtures. The dynamic modulus test results indicate that the dynamic modulus values of the high modulus mixtures are higher than those of the conventional mixtures by 10~15% at 5℃, 20~25% at 15℃ and 100% at 30℃. It is observed from the performance tests that the high modulus mixtures yield better fatigue, rutting and moisture damage performance than the conventional mixtures.


Virtual Reality (VR) and Augmented Reality (AR) have become familiar technologies with related markets growing rapidly every year. Moreover, the idea of considering VR and AR as one eXtended reality (XR) has broken the border between virtual space and real space. However, there is no formal way to create such XR content except through existing VR or AR content development platforms. These platforms require the content author to perform additional tasks such as duplicating content for a specific user interaction environment (VR or AR) and associating them as one. Also, describing the content in an existing markup language (e.g., X3D, X3DOM, A-frame) has limitations of that the content author should predefine the user interaction environment (i.e., either of VR and AR). In this study, a unified XR representation is defined for describing XR content, and the method to render it has been proposed. The unified XR representation extends the HTML so that content authored with this representation can be harmoniously incorporated into existing web documents and can exploit resources on the World Wide Web. The XR renderer, which draws XR content on the screen, follows different procedures for both VR and AR situations. Consequently, the XR content works in both user interaction environment (VR and AR). Hence, this study provides a straightforward XR content authoring method that users access anywhere through a web browser regardless of their situational contexts, such as VR or AR. It facilitates XR collaboration with real objects by providing both VR and AR users with accessing an identical content.


Synthetic diamonds with nitrogen concentrations higher than previously reported in the literature are found to operate very effectively as alpha-particle detectors, as well as detectors for gamma radiation, when operated as ionisation chambers. Certain of the specimens exhibited extensive linear response characteristics when subjected to either alpha particles or gamma radiation of various dose rates. For alpha particles, the response of the detectors at constant particle flux was also found to increase linearly with increasing alpha-particle energy. Unlike previously reported investigations, however, the variation in the response of the synthetic stones to gamma radiation as a function of time was found to be not only more rapid but also to be virtually unaffected by illumination with intense white light.


Smart cities are typical examples of distributed cyber-physical systems because they closely integrate multiple technical and social domains providing novel solutions to improve the cities' ecological footprint. Smart city architectures couple these domains and thus have to cover manifold control loops of different characteristic time constants. The wide granularity spectrum and multiple domains make modeling and simulation of smart cities a challenging task. In this paper, we present a greenfield architecture considering buildings, electric power grid, and communication infrastructure. This idealized blueprint architecture is created based on the real field situation in the smart city project of Aspern - Vienna's Urban Lakeside. We present the specific goals of the flagship research project "Smart Cities Demo Aspern" and how they are fulfilled by the presented greenfield architecture. The greenfield architecture is developed to provide an additional reference besides related Smart City Projects, against which the real-world implementation can be assessed. It also helps to understand the wide granularity spectrum that a technical smart city system has to cover, and thus allows to draw conclusions for the modeling of such cyberphysical systems of systems.


In general education at the college level to prioritize quality of service as the primary goal, because the quality of service quality is a major factor to demonstrate the performance of the organization will be the desire and commitment of stakeholders. This study aims to analyze the influence of leadership on employee performance and its effect on the quality of service. Object of this study is its staff Polytechnic Batam, Riau Island. The samples were 50 employees lecturer. Data were collected using a questionnaire. The findings of this study indicate that the value of R square is 0.681. Shows the value of effective leadership and faculty performance is quite good, will raise the quality of service at the Polytechnic of 68.1%. Subsequent research findings employee performance variables lecturer dominant influence on the quality of service quality in Batam Polytechnic of 55.9%


Objectives:The public health implications of regional variation in incidence and outcome of severe traumatic injury remain to be analyzed. The objective of this study was to determine whether the incidence and outcome associated with severe traumatic injury differs across geographic regions of North America. Methods:A prospective, observational study was conducted of the Resuscitation Outcomes Consortium of all patients in 9 North American sites (6 US and 3 Canadian) sustaining severe traumatic injury from April 1, 2006 to March 31, 2007 followed to hospital discharge. Eligible patients were assessed by organized emergency medical services, and had field-based physiologic criteria including systolic blood pressure ≤90 mm Hg, Glasgow Coma Scale score ≤12, respiratory rate <10 or >29 per minute, advanced airway procedure, or traumatic death in the field. Census data were used to determine rates adjusted for age and sex. The main outcome measures were incidence rate, mortality rate, case fatality rate, and survival to discharge for patients sustaining severe traumatic injury assessed by EMS. Results:The total catchment population of 20.5 million yielded 7080 cases of severe traumatic injury. Median age was 36 years and 67% were male. The median incidence of EMS-assessed severe traumatic injury per 100,000 population across sites was 37.4 (interquartile range [IQR] = 24.6–69.6); survival ranged from 39.8% to 80.8%, with a median of 64.5% (IQR = 55.5–78.4). About 942 cases were pronounced dead at the scene and 5857 patients were transported to hospital; 4477 (63.2%) were discharged alive. The median incidence of severe trauma due to a blunt mechanism, transported to hospital, was 25.8 (IQR = 13.1–44.3); survival ranged from 52.6% to 87.3%, with a median of 78.0% (IQR = 68.4–83.5). The median incidence of severe penetrating trauma, transported to hospital, was 2.6 (IQR = 1.5–10.4); survival ranged from 37.5% to 84.7%, with a median of 67.5% (IQR = 54.1–75.9). All P values for differences across sites for incidence and survival were <0.001. Conclusions:In this study involving 9 geographic regions in North America, there were significant and important regional differences in severe traumatic injury, incidence, and outcome. These differences were sustained for patients with either isolated blunt or penetrating injury mechanisms.


This research investigates the role of worker–firm matching algorithms in accounting for early job separation rates. For this purpose, we examine Korea's temporary foreign worker program in which the government classifies firms by priority level and matches them with foreign workers on the basis of their stated preferences. Using administrative data, we examine predictors for the job separation rates and propose alternative matching methods using serial dictatorship. Our simulation results show that alternative matching methods can substantially reduce job separation rates, thereby suggesting a possible improvement of the Korean program.


The recent decision by the South African Health Department to withdraw the provision of free replacement (formula) feeds to HIV-exposed infants has hardly evoked any response from clinicians, health professionals or civil society groups. This paper argues that the decision is short-sighted, lacks an adequate evidence base, and is retrogressive and unconstitutional. Nine supporting arguments are presented and an alternative policy proposed.


Background : High doses of inhaled corticosteroids (ICS) can increase risk of type 2 diabetes, osteoporosis and pneumonia (Price, D. et al. Prim Care Respir J 2013; 22:92-100). Aim : To characterise prescribing patterns for UK COPD patients with comorbidities or history of pneumonia commencing first maintenance therapy for COPD. Methods : Retrospective observational study, using Optimum Patient Care Research Database, of patients prescribed first maintenance therapy for COPD (ICS, long-acting β agonist [LABA], long-acting muscarinic antagonist [LAMA] or combination) in 2009-2012 at or after COPD diagnosis confirmed by spirometry. Study period was 1 year before and 1-3 years after prescription for therapy. Therapy, comorbidities and history of pneumonia were recorded. Results : Of 2217 patients (55% male; 45% smokers; 47% ex-smokers; 22% aged ‹60 years; 54% 60-75 years; 24% ≥75 years) 24%, 11%, 7% and 17% had, at any time, diabetes and/or therapy, osteoporosis, history of pneumonia and asthma, respectively. Conclusion : ICSs and their combinations are prescribed frequently for COPD patients with diabetes, osteoporosis and history of pneumonia, who might be more at risk of ICS side effects, while bronchodilator monotherapy is prescribed frequently for COPD patients with asthma who might benefit from added ICS.


Docking has become an indispensable approach in drug discovery research to predict the binding mode of a ligand. One great challenge in docking is to efficiently refine the correct pose from various putative docking poses through scoring functions. We recently examined the stability of self-docking poses under molecular dynamics (MD) simulations and showed that equilibrium MD simulations have some capability to discriminate between correct and decoy poses. Here, we have extended our previous work to cross-docking studies for practical applications. Three target proteins (thrombin, heat shock protein 90-alpha, and cyclin-dependent kinase 2) of pharmaceutical interest were selected. Three comparable poses (one correct pose and two decoys) for each ligand were then selected from the docking poses. To obtain the docking poses for the three target proteins, we used three different protocols, namely: normal docking, induced fit docking (IFD), and IFD against the homology model. Finally, five parallel MD equilibrium runs were performed on each pose for the statistical analysis. The results showed that the correct poses were generally more stable than the decoy poses under MD. The discrimination capability of MD depends on the strategy. The safest way was to judge a pose as being stable if any one run among five parallel runs was stable under MD. In this case, 95% of the correct poses were retained under MD, and about 25-44% of the decoys could be excluded by the simulations for all cases. On the other hand, if we judge a pose as being stable when any two or three runs were stable, with the risk of incorrectly excluding some correct poses, approximately 31-53% or 39-56% of the two decoys could be excluded by MD, respectively. Our results suggest that simple equilibrium simulations can serve as an effective filter to exclude decoy poses that cannot be distinguished by docking scores from the computationally expensive free-energy calculations.