Agent Oriented Software Engineering (AOSE) is one of the fields of the agent domain with a continuous growing interest. The reason is that the possibility to easily specify and implement agent-based systems is of a great importance for the recognition of the add-value of the agent technology in many application fields. In this paper we present an attempt towards this direction, by proposing a kind of roadmap of how one can combine the MaSE methodology for agent-oriented analysis and design and JADEX, a FIPA compliant agent development framework, for an easier analysis, design and implementation of multi-agent systems. Our objective is realized through the presentation of the analysis, design and implementation phases, of a water treatment plant information management system.


Hepatitis B virus (HBV) infection occurred despite full passive-active immunoprophylaxis in 20 of 321 infants born to mothers seropositive for hepatitis B e antigen. In 2 (12%) of 17 infected infants, mother-infant DNA sequence mismatches were found in a segment of the HBV S gene coding for antigenic determinants of the HBV surface antigen (HBsAg) amplified from sera by polymerase chain reaction (PCR). Point substitutions occurred in codons 120, 134, and 144 of the HBsAg polypeptide in the variant sequence of 1 infant and in codon 126 in the other; all were missense mutations. Mutant sequences could not be recovered from maternal sera by PCR cloning but were selectively generated using an amplification refractory mutation system. The frequency of potential vaccine escape mutants is therefore low, and these preexist maternally as minor variants.


Background: Osteoporosis projects a dominant issue related to health in the community in developing country like ours –India and is often unrecognised or undiagnosed. Early Diagnosis and treatment of osteoporosis is of utmost importance. This study evaluates the accuracy of Radiological Indices in comparison to gold standard DEXA scan for diagnosis of osteoporosis, so that diagnosis of Osteoporosis can be done using simple radiographs which would be cost effective and less exposure to radiation. Methods and Material: The is study is a one year hospital based comparative study which included a total of 80 patients who presented to OPD / IPD of Department of Orthopaedics and met the inclusion criteria were enrolled in the study. Patients were subjected to DEXA scan and a plain radiograph of either of the hip joint with full length femur in AP and Lateral views. Subsequently, the Singh's Index, Cortical Thickness Index(CTI) AP and Lateral, Calcar to Canal Ratio (CCR) were measured and compared with the standard DEXA scan. Statistical analysis used: Spearman's Rank co-efficient was used to find correlation between Radiological Indices and DEXA scan, Kappa Statistics for level of agreement, Sensitivity and Specificity for Radiological Indices was calculated. Results: The data analysed showed significant correlation (Spearman co-efficient) between Radiological Indices and DEXA scan. Cortical thickness index Antero-posterior view and Lateral view with cut-off 0.43(r=0.8172, p< 0.0001 and r=0.8243, p< 0.0001 respectively), calcar to canal ratio with cut-off 0.50 (r=0.8188, p< 0.0001). Similarly for Singh's Index (r=0.6002, p< 0.0001). Conclusion: Radiological indices are reliable in the diagnosis of Osteoporosis and have a good correlation with T scores decuded by DEXA scan.


This paper presents comparisons between measured and predicted pressure stability on the suction side of an oscillation blade at an inlet Mach number of 0.5, with oscillation frequencies from 60 to 210Hz, mean incidence angles from 0° to 10° and with blade amplitudes up to 4.2° (for 60Hz). It was found from the experiments that an increased mean incidence caused a higher excitation of the blade from the aerodynamic forces, while the effects of varying the blade amplitudes and frequencies were more difficult to determine. The timedependent pressures show that the aerodynamic loads are not linear for the stall region. At 6° mean incidence angle, and below, increased blade amplitude for a constant frequency caused the blade suction surface to experience an increased excitation, while for the 7° incidence, and above, the opposite was shown. The fact that the blade amplitude dependence changes when the mean incidence increases above the steady state stall angle is explained by the increased portion of the oscillation cycle spent at stalled conditions. A shift in phase was seen for the highest investigated frequency, which at the time of the experiments was thought to be due to a phase lag between the blade motion and the leading edge vortex, increasing with increasing frequency. The numerical modelling is based on an implicit finite volume approach with a third order upwind scheme and a Riemann solver. The results showed that flow transition plays a key role in the blade stability during high frequency oscillation, with the transition location influenced not only by incidence angle but also oscillation frequency. With a model varying the transition onset it was possible to predict the phase shift seen in the experiments even for low angles of attack. Background and Objectives Flutter of turbomachinery blades is a crucial problem in aircraft propulsion since it reduces the operational envelope of aeroengines and the useful life of their blades. Due to its profound importance blade flutter has been the subject of several investigations [Choudhuri and Knight, 1996; Daube et al., 1985; He and Denton, 1991; Jones and Platzer, 1997] and in recent years significant progress has been made in flutter prediction using Computational Fluid Dynamics coupled with modal structural representation of the blades. The present paper deals with a fundamental problem of aerodynamic stability of turbomachinery blades and attempts to simulate an idealized flutter situation of a thin lifting section. Of central importance is the relationship between the loading of the blade and the flow angle and any phase difference between the two. Furthermore, this paper reveals the demands on CFD for accurately predicting blade flutter both in terms of flow physics and especially turbulence and transition modeling. The current effort builds on previous experimental work by Svensdotter et al. [1997, 1998, 1999, 2000] using transonic flow tunnels and instrumented thin blade sections. It is the objective of this paper to take further the previous experimental and theoretical study using Computational Fluid Dynamics and attempts to shed more light in the fundamental problem of blade stability at transonic flow conditions. The paper begins with an outline of the experiment and the main conclusions drawn from it and continues with the CFD investigation. Analysis of the obtained results and comparisons against experiments is presented and conclusions are finally drawn along with suggestions for future work. Description of the Experiment The wind tunnel used for the experiments was wind tunnel No 5 at Volvo Aero Corporation which is connected to a large air reservoir providing the tunnel with dried air of constant inlet conditions for continuous testing [Kemppainen, 1995]. The test section is 150mm*180mm and is described in detail by Svensdotter et al. [1997]. The inlet Mach number can be varied continuously from 0.3 to 1.6 and the inlet stagnation temperature is about 280K [Johansson, 1992]. The free stream static pressure can be varied between slightly below atmospheric pressure and up to 400kPa at Mach 1. At Mach 0.5 the inlet free-stream turbulence intensity is 1.7% [Kemppainen, 1995]. A symmetrical 2D airfoil NACA 63A006 with a chord length of 80mm and a span of 150mm were used for the tests. The profile is equipped with 13 pressure transducers on the suction surface of the blade. Pressure gauges 1-11 are mounted in cavities connected through drilled holes to the surface (∅ 0.6mm). Gauges 12 and 13 are flush mounted with the surface. The pressure sensors are positioned between 5% and 80% chord. During the tests presented in this paper, sensor 11 was broken and sensor 1 broke during the later part of the test series. The airfoil is mounted on a shaft with plain bearings in the side walls. The pitching axis through the shaft is at 43% of the chord and the torque was transmitted to the airfoil by the starboard side shaft. Details of the excitation system can be found in Sjunnesson [1992]. The actuator motion can be detected by a high precision potentiometer on the actuator shaft. The blade frequencies and amplitudes can be seen in table 1. The details of the pressure acquisition system can be found in Svensdotter et al. [1997], as well as discussions concerning the details of the measurement accuracy. The unsteady pressure measurements are performed with an accuracy of ±300Pa, which gives an error in ~ Cp of between ±7 and ±15% of maximum pressure amplitude, considering an error in the blade motion of ±0.05°. The wind tunnel and the experimental setup can be found in Figure 1. To achieve the objectives outlined in the previous section, the following experimental approach was selected. The investigated flow conditions were specified to consist of high oscillating frequencies (up to 210Hz), from attached to above stall conditions. The inlet Mach number was 0.5 and the chord based Reynolds number was 850 000. The details of the oscillation data selected for discussion in the presented study can be found in Table 1. For the frequencies used in the presented investigation, f=60Hz corresponds to k=0.09, f=110Hz to k=0.16 and f=210Hz to k=0.31 respectively. The maximum error in reduced frequency is determined to ±0.01. The unsteady pressure signals were analysed in terms of the amplitude of the perturbation ~ Cp and the phase difference between the pressure signal and the blade motion. The phase angle is positive when the pressure leads the blade and this gives an energy transfer into the blade, i.e. the blade is excited. The amplitude of ~ Cp gives the size of the exciting forces. The measured data is treated with a fast Fourier transform and the amplitude and phase of the unsteady pressure coefficient is based on the first harmonic (Y) of the perturbation ~ Cp, according to: ( ) t i


Nanosized photocatalyst ZnS particles supported on silica and polyvinyl alcohol was successfully prepared by complex trans-formation method. The photoc~jtic reduction of CO2 was carried out in the presence of nanosized ZnS catalyst irradiated by a high-pressure mercury-vapor lamp to give the main products of formaldehyde and ethanol. The catalytic ability of ZnS characterized by the uptaken rate of CO2 volume in the reaction system depended upon the preparing conditions of nanosized ZnS catalysts. Decreasing the concentration of Na2 S and increasing the molar ratio of oxygen in the PVA to Zn^2 + could result in the decreasing of the size of ZnS particles but could not result in the monotonous increasing of the reduction rate of CO2. The mechanism of reduction of CO2 may be related to the H atoms and OH radicals, which form from H2O by transmission of the electron-hole pairs from irradiated the naaosized ZnS.


We have measured the ratios of antiparticles to particles for charged pions, kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] = 130 GeV. We observe / = 1.00+/-0.01(stat)+/-0.02(syst), / = 0.91+/-0.07(stat)+/-0.06(syst), and / = 0.60+/-0.04(stat)+/-0.06(syst). The / and / ratios give a consistent estimate of the baryo-chemical potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb collisions at sqrt[s(NN)] = 17.2 GeV.


The spectrum of Mg-like Br, Br XXIV, was investigated by means of the beam-foil technique. Bromine ions of 90 and 130 MeV energy from the HI-13 tandem accelerator at the China Institute of Atomic Energy were used, and the wavelength region 130–290 Å was investigated. The spectra showed 24 Br XXIV transitions within the n = 3 complex, i.e. between the 3s2, 3s3p, 3p2, 3s3d and 3p3d configurations. Of these 5 have been reported earlier. In this spectrum 19 energy levels have now been experimentally determined, 14 of which have not been reported earlier. The observed energy level values have been theoretically interpreted by means of relativistic Hartree-Fock (HFR) calculations.


Background

SSA/Ro 60 has been reported to be exposed on the surface of early apoptotic cells and recognized by autoantibodies from lupus. The aim of this study was to explore the subsequent effects of the binding of IgG from anti-SSA positive LN patients on the fate of early apoptotic cells.

Results

IgG which have been confirmed with extensive binding to early apoptotic cells were purified from three anti-SSA positive LN patients. Opsonization of early apoptotic cells by IgG from LN augmented C3c deposition without influence on the assembly of the terminal complement components or cell lysis. IgG from LN enhanced opsonization and phagocytosis of early apoptotic cells by macrophages directly or dependent on complement activation, with massive TNF-a and IL-1β secretions.

Conclusions

IgG from anti-SSA positive LN facilitates early apoptotic cell clearance by macrophages and triggers proinflammatory cytokines release, possibly exacerbating underlying pathogenic mechanisms in lupus nephritis.


In this paper we integrate the dynamic models formulated by the microeconomic theory of trade unions and the differential games approach. We demonstrate that the results of the dynamic monopoly union model, elaborated by Kidd and Oswald (1987) and Jones and McKenna (1994), can be obtained as solutions of a Stackelberg differential game between a firm and a union under particular assumptions on union's membership dynamic. We then turn our attention to the cooperative bargaining case, and we show how the optimal threat strategies can be determined, allowing to calculate the threat point payoffs.


A single-blind, short-term cross-over clinical trial compared the plaque removal performance of three commercially available manual toothbrushes. A sample of 25 dental hygiene students, 19 to 42 years old, served as participants. On 3 separate occasions, participants were instructed to refrain from toothbrushing or flossing for 24 hours before clinical trials. A prebrushing plaque index using disclosing solution was performed on each participant. One of the 3 test brushes was then randomly dispensed to each participant, and they were allowed to brush for 90 seconds without the aid of a mirror. A postbrushing plaque index was then performed on each participant. This procedure was repeated 2 more times at 2-week intervals so that each participant was tested with all 3 toothbrushes. Previous studies of this kind using random participant samples have suggested that brush design does indeed affect the efficacy of plaque removal. This study used participants who were well versed on efficient toothbrushing technique to determine if improved brushing skills would overshadow advantages in toothbrush design. No significant differences in performance were detected between the test brushes for any of the three scored areas.


Dopamine has an important role in normal cognition and reward processing, both of which are impaired in disorders involving dopamine dysfunction such as addiction, schizophrenia, and Parkinson's disease. However, our understanding of the interplay between different aspects of the dopamine system and reward-guided behavior in humans is limited. Food is an important type of reward that is critical for survival and impacts the decisions we make every day. Here, we characterize the relationship between two food-reward related phenotypes and dopamine synthesis capacity (related to tonic dopamine) as well as dopamine D1 and D2 receptor availability in healthy humans. First, we examined the link between dopamine synthesis and receptor availability and body mass regulation in 117 individuals with body mass index (BMI) values ranging from normal to obese. We found that current BMI was related to a pattern of increased dopamine synthesis in the hypothalamus, a region important for homeostatic control of appetite, but decreased dopamine D 2 receptor availability in the midbrain, where D 2 autoreceptors regulate dopamine release throughout the brain. This suggests that increased BMI is related to a dopamine imbalance between homeostatic drivers of appetite and reward system regulatory control mechanisms that could result in an overactive, unregulated intake of food. Building on this finding, we studied the link between dopamine synthesis capacity and receptor availability and an important food-reward related behavior, foraging. Fifty-seven healthy volunteers completed a computer-based foraging task where we measured their threshold for leaving one group of rewards to search for another in four different reward environments varying from a low to high rate of reward receipt. We found that two particular patterns of dopamine synthesis and receptor availability in the anterior cingulate cortex and basal ganglia were linked to the amount that individuals changed their threshold based on the reward rate of the environment. Finally, since the prefrontal cortex is known to be important for reward-guided behavior, we implemented two methodological advancements aimed to address limitations that make it difficult to measure cortical dopamine in humans with PET imaging. The first method involves partial volume correction and surface-based smoothing in order to increase the signal to noise in the cortex. The second method is a data-driven PET data parcellation and automated reference region selection algorithm to optimize the voxels included in the reference region. In conclusion, we have characterized the dopaminergic contribution of two different foodreward guided phenotypes and have developed two techniques that will aid future research on the role of cortical dopamine. Understanding the neural mechanisms underlying these rewardguided behaviors helps us to not only understand normal behavior, but also serves as a reference for comparison when studying related pathological states.


In this research work we have developed a strategy in which the various parameters that influence the occurrence of pulmonary disease have been gathered from survey of doctors who specialize in diagnoses of pulmonary disease and diagnostic recipes involving if the else rules were built and given labels, which were used as target for machine learning algorithms [Logistic , SVM, RBF, Naïve Bayes ] for identification of input dataset of symptoms of subjects . Multiple designs of these classifiers were implemented and best possible machine algorithm was identified for implementing the complete methodology. Results shows that there was no absolute answer for the design and selection of best possible machine algorithm as evident from the results based on multiple statistical tests, therefore , distance from ideal values of statistical test to find best classifier with most optimized parameters was calculated and the classifier which had closest to these ideal values was found and declared the best classifier for identification of pulmonary diseases presence or absence .as per results naïve bayes classifier is performing best which is evident from the statistical test scores .


Evidence of a relation between the mass accretion rate and the disk mass is established for young, Class II pre-main-sequence stars. This observational result opened an avenue to test theoretical models and constrain the initial conditions of disk formation, fundamental in the understanding of the emergence of planetary systems. However, it is becoming clear that planet formation starts even before the Class II stage, in disks around Class 0 and I protostars. We show for the first time evidence for a correlation between the mass accretion rate and the disk mass for a large sample of Class I young stars located in nearby (<500 pc) star-forming regions. We fit our sample, finding that the Class I object relation has a slope flatter than Class II stars, and the former have higher mass accretion rates and disk masses. The results are put in context of disk evolution models.


The article summarizes the results of the historical and philosophical research "Collection of ancient stories" (Konjaku monogatari-shū, 1120s). This largest Japanese collection of setsuwa tales paints a picture of world history from the era of Buddha to the age of mappō, "Decline of Buddhist Teaching", tracing the milestones in the spread of Buddhism in India, China and Japan. The two most important Buddhist attitudes – the world is impermanent and at the same time each event is embedded into a universal system of cause-and-effect relationships – are reflected not only at the level of the content of an individual story, but also at the level of connecting stories into a holistic narrative. All events have instructive educative? meaning; everyday experience always leads to the same conclusions as the teachings of Buddha. In this experience, a person inevitably makes some connections – with other people, living and dead, with animals and spirits, gods and buddhas – and these connections involving this person in the cycle of birth and death, if properly understood, provide the basis for liberation. The narrator draws a line between a proper and an inappropriate understanding of what is happening, talking about the "immeasurable" (grief, joy, fear, etc.), and thus allows the readers to find the "measure", kagiri, in their relation to what is happening. The march of time can be understood both as a general movement from the best to the worst, and – on small intervals – as a reverse movement from grief to happiness, from misunderstanding to understanding. A person is free to choose which events to keep in memory and which to forget; people make this choice whilst instructive storytelling, and setsuwa tradition preserves it.


ABSTRACT This paper explores how news organizations visualize crises in a digital media ecology shaped by citizen witnessing and widespread image circulation on social media. Empirically, the paper draws on the events of 7 April 2017 in Stockholm when a hijacked truck plowed into crowds, killing five and injuring several others. The study is informed by theoretical perspectives and research on citizen photojournalism and witnessing, and examines the function of visual citizen contributions, degrees of explicitness in visual coverage and the impact of proximity on visualizations of crises. Qualitative analyses of visual content and text in digital and print editions of four Swedish newspapers showed both enhancing and featured positioning of visual eyewitness contributions from the public, few examples of explicit imagery, and journalistic commentary foregrounding ethical dimensions of showing and seeing. Based on the findings, the author considers journalism's civic response as a strategy for staking a claim to credibility and ethics at a moment when the journalistic gatekeeping position is called into question.


The Role of Intrinsically Disordered Thellungiella salsuginea dehydrins TsDHN-1 and TsDHN2 in Stabilization of Membranes and Cytoskeletal Actin Filaments Luna N. Rahman Advisors: University of Guelph, 2102 Professor George Harauz Professor John Dutcher The group 2 late embryogenesis abundant (LEA) proteins, also known as the dehydrins, are intrinsically disordered proteins that are expressed in plants experiencing extreme environmental conditions such as drought or low temperature. In this work, we study the potential roles that dehydrins may have in stabilizing membranes and actin microfilaments during cold stress. We have cloned and expressed in E. coli two dehydrins from Thellungiella salsuginea, denoted TsDHN-1 (acidic) and TsDHN-2 (basic). These proteins were expressed as SUMO-fusion proteins for in vitro phosphorylation by casein kinase II (CKII), and for structural analysis by CD and Fourier transform infrared (FTIR) spectroscopy. We show using transmission-FTIR spectroscopy that ordered secondary structure is induced and stabilized in these proteins by association with large unilamellar vesicles emulating the lipid compositions of plant plasma and organellar membranes. The increase in secondary structure by membrane association is further facilitated by the presence of Zn. Lipid composition and temperature have synergistic effects on the secondary structure. Our single molecule force spectroscopy studies also suggest tertiary folding of both TsDHN-1 and TsDHN-2 induced by association with lipids. From Langmuir-Blodgett monolayer compression studies, and from topographic studies using atomic force microscopy at variable temperature, we conclude that TsDHN-1 stabilizes the membrane at lower temperatures. Finally, we show that the conformations of TsDHN-1 and TsDHN-2 are affected by pH, interactions with cations and membranes, and phosphorylation. Actin assembly by these dehydrins was assessed by sedimentation assays, and viewed by transmission electron and atomic force microscopy. Phosphorylation enabled both dehydrins to polymerize actin filaments, a phenomenon that may occur in the cytosols of plant cells undergoing environmental stress. These results support the hypothesis that dehydrins stabilize plant organellar membranes and/or the cytoskeleton in conditions of stress, and further that phosphorylation may be an important feature of this stabilization.


Understanding Zeno phenomena plays an important role in understanding hybrid systems. A natural - and intriguing - question to ask is: what happens after a Zeno point? Inspired by the construction of Filippov (1988), we propose a method for extending Zeno executions past a Zeno point for a class of hybrid systems: Lagrangian hybrid systems. We argue that after the Zeno point is reached, the hybrid system should switch to a holonomically constrained dynamical system, where the holonomic constraints are based on the unilateral constraints on the configuration space that originally defined the hybrid system. These principles are substantiated with a series of examples


Many researchers have studied the thermal state of the crust and the upper mantle and its tectonic implications in Hokkaido, Japan. Terrestrial heat flow data have revealed the following characteristic features: (1) High heat flow (84〜125 mW/m2) is observed in the backarc side of the volcanic front, while low heat flow (< 42 mW/m2) is observed in the forearc side, showing the typical thermal aspects of the island arc. (2) The central axis zone of Hokkaido (the Kamuikotan and Hidaka metamorphic belts) shows relatively low heat flow (42〜80 mW/m2). The low heat flow zone extends for Sakhalin. (3) Extremely low (25〜34 mW/m2) and high (125 〜 210 mW/m2) heat flow is distributed locally on the Ishikari-Tomakomai low land and its neighbor on the west, respectively. Based on the heat flow data and other geophysical data, such as the seismic velocity structure, aeromagnetic data, and so on, the Curie point depth, the solidus temperature depth, temperature at the Moho, and the mantle heat flow have been estimated. The estimated thermal structure implies the temperature of the lower crust comes to the solidus temperature beneath the backarc side of Hokkaido. The result is well supported by the electrical resistivity soundings: the low resistive layer (10~40 ohm-m) develops in the lower crust and is ascribed to the effect of partial melting of the crustal rocks.


Group A streptococcal strains vary widely in the amount of hyaluronic acid capsule they produce, although the has operon, which encodes the enzymes required for hyaluronic acid synthesis, is highly conserved. The three genes making up the has operon are transcribed from a single promoter located upstream of the first gene in the operon, hasA. To investigate transcriptional regulation of capsule synthesis, we studied the structure and function of the has operon promoter sequences from two strains of group A Streptococcus: a highly encapsulated M‐type 18 strain and a poorly encapsulated M‐type 3 strain. Transcriptional fusions of the has operon promoter to a promoterless chloramphenicol acetyltransferase gene were constructed in a temperature‐sensitive shuttle vector. The influence of promoter structure on has operon transcription was reflected by chloramphenicol acetyl transferase activity in cell lysates of Escherichia coli harbouring the recombinant plasmids and in group A Streptococcus after integration of the promoter fusions into the streptococcal chromosome. Fusions including as few as 12 nucleotides upstream from the −35 site of the has promoter exhibited full activity, indicating that sequences further upstream do not affect has gene transcription. A transcriptional fusion of the has promoter from the highly encapsulated M‐type 18 strain was threefold more active than a similar construct from the poorly encapsulated M‐type 3 strain. Analysis of the promoter sequences for the two strains revealed differences in three nucleotides in the −35, −10 spacer region of the promoter and in four nucleotides in the + 2 to + 8 positions relative to the start site of hasA transcription. To determine the relative importance of the two groups of nucleotide substitutions, chimeric promoter sequences were constructed in which either of the two clusters of variant nucleotides from the M18 has promoter was substituted for the corresponding positions in the M3 has promoter. Analysis of these chimeric promoter fusions showed that sequence changes in both regions influenced promoter strength. These results define the limits of cis‐acting chromosomal sequences that influence transcription of the has operon and indicate that the fine structure of the promoter is an important determinant of capsule gene expression in group A Streptococcus.


The effect of removal of external Ca2+ on phosphoinositide hydrolysis was investigated in cultured myotubes from 9-day-old Leghorn embryonic chicken. In the myotubes exposed to Ca(2+)-free Ringer's solution, the turnover of phosphoinositide was exponentially decreased with a time constant of about 26 min. In the presence of external Ca2+, the hydrolysis of phosphoinositide was significantly increased by exposure to 80 mmol/L K+ solution. After removal of external Ca2+, 80 mmol/L K+ exposure caused a slight decrease of phosphoinositides hydrolysis in comparison with the control (normal Ringer). It is indicated that hydrolysis of phosphoinositide in cultured myotubes can be enhanced by high K+ exposure. External Ca2+ is essential for this effect, which is different from mature muscle fibres.


Following a three-dimensional inverse modeling study on atmospheric CO mixing ratios [Bergamaschi et al., this issue], we present the expansion of our model for the treatment of the stable isotope ratios 13C/12C and 18O/16O in carbon monoxide. The individual isotopomers were included in the model as independent tracers, and the inversion scheme was extended, allowing the simultaneous optimization (with respect to observational data) of modeled atmospheric mixing and isotope ratios. Observational data of 13C/12C and 18O/16O ratios were taken from a set of five globally distributed sites, all of which exhibit pronounced seasonal cycles and which as a whole clearly define large latitudinal gradients. Incorporation of 13C/12C ratios in the inversion resulted in a clear constraining of the total amount of CO arising from CH4 oxidation. The present study suggests an average CO yield of 86% (80–88%), provided that (1) the reaction of CH4+Cl has no significant impact on the δ 13C of the resulting CO and (2) CO from the ocean helps to balance the δ13C in the Southern Hemisphere. Otherwise, a further reduced CO yield would be necessary, as low as 71% in case of an average kinetic isotope effect of 1.013 [Lowe et al., 1999] or 69% in case of a δ13C value of −25.0‰ for the oceanic source. Despite a lack of experimental investigations on 18O/16O in CO arising from CH4 or nonmethanehydrocarbons (NMHC) oxidation, inclusion of 18O/16O into the inversion gives further significant constraints on the global CO cycle. It is shown that apart from the large technological CO source, additional sources with dominant emissions in the Northern Hemisphere are required, such as biogenic emissions (either direct or via oxidation of biogenic NMHCs) or anthropogenic NMHCs, in order to reproduce observed atmospheric 18O/16O ratios. The extended inversion scheme allows CO budgets to be derived, which reproduce, within two standard deviations of observational data, simultaneously CO mixing ratios (from the National Oceanic and Atmospheric Administration Climate Monitoring and Diagnostics Laboratory network), 13C/12C, and 18O/16O ratios. Incorporation of stable isotopes renders inversion results much more robust compared to inversions of CO mixing ratios only.


The aim of the study was to survey fungal endophytes inhabiting healthy leaves and stems of evergreen rhododendrons and during in vitro tissue culture for their propagation. Fungi were identified using morphological traits. The main taxa observed in rhododendron leaves in vivo were Phomopsis, Phoma, Alternaria spp., Colletotrichum, Cladosporium, Seimatosporium, Diplodina, Coleophoma, Cryptocline, Truncatella and Guignardia spp. Contamination in tissue culture were caused by Penicillium, Cladosporium, and Cephalosporium spp. The study supported the view that endophytes can infect medium of in vitro cultivated rhododendrons. Fungal diversity increased after acclimatization of rhododendron plantlets ex vitro. The presence of microorganisms in rhododendron cultivated in vitro depended both on age of tissue and host genotype.


Mirror symmetry is a plausible candidate for a fundamental symmetry of particle interactions which can be exactly conserved if a set of mirror particles exist. The properties of the mirror particles seem to provide an excellent candidate to explain the inferred dark matter of the Universe and might also be responsible for a variety of other puzzles in particle physics, astrophysics, meteoritics and planetary science. One such puzzle\char22{}the orthopositronium lifetime problem\char22{}can be explained if there is a small kinetic mixing of ordinary and mirror photons. We show that this kinetic mixing implies the existence of ordinary atom\char21{}mirror-atom bound states with interesting terrestrial and astrophysical implications. We suggest that sensitive mass spectroscopic studies of ordinary samples containing heavy elements such as lead might reveal the presence of these bound states, as they would appear as anomalously heavy elements. In addition to the effects of single mirror atoms, collective effects from embedded fragments of mirror matter (such as mirror iron microparticles) are also possible. We speculate that such mirror matter fragments might explain a mysterious UV photon burst observed coming from a laser irradiated lead target in a recent experiment.


Using the concept of business models can help companies understand, communicate, share, change, measure, simulate and learn more about the different aspects of e-business in their firms. Better understanding of e-business models helps managers and related staffs to better apply the business model. The main objective of this paper is to use Causal Loop Diagram (CLD) as a useful tool to capture the structure of e-business systems in order to achieve a better understanding of an e-business model. The proposed CLD gives a helpful insight which is useful for managers to learn more about the e-business


The purpose s of th is research was to determine the effect of health education about foot exercise by using audio visual media for increasing knowledge of foot exercise among DM patients type 2. The design of this study was q uasy experiment. 30 respondents was taken by purposive sampling method. The instrument used this questionnaire that had been tested for validity & reliability (0,933) . The result showed the effect of health to improve knowledge of foot exercises implementation in respondents with type 2 of DM in the experimental group after giving the health education was siqnificant ( p value 0.002 <α 0.05 ) . The results of this study recommends that the health workers provide health education by using audio-visual media to enhance knowledge of the diabetic patient to do foot exercise and prevent the occurrence of complications of diabetic, especially in the legs. Keywords  : audio visual media, foot exercises, health education, knowledge References : 62 (2004-2013)


We are still at an early stage of assessing oxytocin-based therapy for autism spectrum disorders The U.S. Centers for Disease Control and Prevention estimates the prevalence of autism spectrum disorders (ASDs) to be 1 in 68 children in the United States, yet no drugs to treat the debilitating social deficits of ASD are available. Oxytocin, a natural brain peptide produced in the hypothalamus, has received considerable attention as a potential treatment for social deficits in ASD. Acute intranasal oxytocin temporarily enhances social cognition, empathy, and reciprocity in individuals with ASD (1). However, recent clinical trials have yielded mixed results, leaving the field questioning whether oxytocin can live up to the hype.


Metal ions are critical nutrients, yet overaccumulation of these same metals can also be toxic. To maintain appropriate intracellular levels, cells require specific metal uptake systems that are subject to precise homeostatic regulation. The long-range goal of our research is to define the molecular mechanism(s) and regulation of metal ion uptake in eukaryotic cells. Integrating genetic, molecular biological and biochemical approaches, we have examined these processes in the yeast Saccharomyces cerevisiae and the plant Arabidopsis thaliana. Both are proven model systems for studying fundamental cellular processes. Our work has focused on the ZIP family of metal transporters which we identified; this family has representatives in bacteria, fungi,plants and animals. IRT1, one of the founding members of the ZIP family, is an essential cation transporter that is expressed in the epidermal cells of iron deficient plant roots and is responsible for uptake of iron from the soil. We now know that t here are 15 ZIP genes in the Arabidopsis genome which can be divided into four different classes, based on their intron/exon arrangements and the similarities among their encoded gene products. The ZIP family members display different substrate specificities for metals and different tissue distributions in Arabidopsis.Moreover, the family members respond differentially to metal deficiencies. For example, IRT1, ZIP6 and ZIP9 mRNA are expressed mainly in the roots of iron deficient plants whereas ZIP4 responds to both iron and zinc deficiency. Work in both yeast and Arabidopsis has addressed substrate specificity as well as how these transporters are regulated in response to metal availability. Our project was broken down into four specific aims. Significant progress was made on all four aims. I have listed the publications which have resulted under the relevant specific aim.


Recent studies that analyze the cytotoxic and pro-carcinogenic effects of estrogens indicate an increased risk of ovarian cancer in those patients which are treatment and do not exclude the effect of excessive hormonal levels on the formation of morphological and functional changes in tissues and organs in future offspring. The aim of the study was to study the effects of the prenatal effects of subtoxic doses of synestrol on the general morphology, histometric and immunohistochemical parameters of the ovaries of the offspring of laboratory mice in the its postnatal reproductive period of ontogenesis. Pregnant female laboratory mice were divided into 3 groups. The control group of animals was once injected olive oil at a dose of 0,2 μg/kg intramuscularly. The first experimental group of animals was injected intramuscularly a single dose of synestrol at a dose of 25 μg/kg in the form of a 2% oil solution, the second experimental group was injected intramuscularly once a single subtoxic dose of synestrol of 40 μg/kg in the form of a 2% oil solution. All pregnant female mice were treatment drugs at the gestational stage of E11.5. A histological study of the preparations of the ovaries of the offspring of the first experimental group of mice showed a change in the ratio of the area of cortical substance relative to the area of the medullar substance with a decrease in the number of follicles at different stages of development compared with similar indicators of the offspring of the control group of animals. A single intramuscular injection of synestrol at a dose of 40 μg/kg in the offspring of the second experimental group led to an increase in the area of cortical and medullar substances of the ovaries, a decrease in the number of primordial, primary (unilaminar) follicles, in contrast to the ovaries of the control group. In histological sections of the ovaries of the second experimental group, hypertrophy and hyperplasia of granulosa cells, as well as teca interna follicles were observed. The appearance of atretic bodies, focal luteinization, indicating a real prenatal effect of the hormone on the postnatal structure of the organ, was noted in the cortical substance. A decrease in the activity of markers of cell proliferation, the transcription factor p53 of an anti-oncogene, indicated damage to ovarian functions at the level of their molecular genetic predictors. The results of the study generally showed that the effect of a subtoxic dose of synestrol at stage E11.5 of the prenatal period of development of the offspring of laboratory mice leads to persistent morphological changes in their ovaries in the postnatal reproductive period of ontogenesis.


This book supports teachers of all subject specialisms to consolidate their existing knowledge of language and shows them how to develop skills to use language to build subject knowledge at secondary level. Tasks guide the reader to think about the language we use for different purposes, and how we use it to describe, explain and learn about our world. This paves an accessible way for subject-related language to become more visible and enables readers to use accessible terminology to confidently talk about it, as well as modelling it and guiding the development of its use with all learners, including those with English as an Additional Language (EAL).

Starting from basic educational principles, the book asks readers to consider the processes of learning and why every good teacher needs knowledge about language to support this, addressing a range of questions including:
Who are the EAL learners?
What are the processes of language development?
How is language used to present and discuss knowledge in my subject?
Why does every good teacher need knowledge about language to support subject literacy?

The authors provide examples, discovery tasks, reflections and templates for activities, to help the reader identify the tools they need to set up a framework for scaffolding pupils' language development. With a progression plan, directed tasks, and formative feedback, this framework provides a template for classroom practice and further professional development.


Highly textured pure and Al doped ZnO thin films have been produced by pulsed laser deposition for optical gas sensor application. The influence of the processing parameters such as substrate temperature and oxygen pressure applied during depositions, and dopant concentration on the structural, morphological, and optical properties of the films were investigated. All deposited films are textured along the (002) direction. The substrate temperature and the oxygen pressure have stronger influence on the film crystallinity compared to the presence of the dopants. The grain size of the films prepared from 2 wt% Al2O3 doped ZnO target is approximately the same as the one produced from pure ZnO tagret. The increase in the dopant concentration into the ZnO target (to 5 wt% Al2O3) leads to an increase of the in-plane grain size of the as-deposited films which is well known to increase the gas sensitivity. At the same time, the use of doped targets increase the droplets on the film surface which deteriorates the optical detection of the gas sensing effect. The increase of the dopant concentration reduces the film transmission in the visible range and the transmission cut-off edge is shifted to the shorter wavelengths. The films deposited from 2 wt% Al2O3 doped ZnO target at oxygen pressure of 0.05 mbar and 300°C substrate temperature have good mode properties which makes them good candidates for optical sensors.


Large, spontaneous m/n = 1/1 helical cores are predicted in tokamaks with extended regions of low- or reversed-magnetic shear profiles in a region within the q = 1 surface and an onset condition determined by constant (dp/dρ)/Bt2 along the threshold. These 3D modes occurred frequently in Alcator C-Mod during ramp-up when slow current penetration results in a reversed shear q-profile. The onset and early development of a helical core in C-Mod were simulated using a new 3D time-dependent equilibrium reconstruction, based on the ideal MHD equilibrium code VMEC. The reconstruction used the experimental density, temperature, and soft-X-ray fluctuations. The pressure profile can become hollow due to an inverted, hollow electron temperature profile caused by molybdenum radiation in the plasma core during the current ramp-up phase before the onset of sawteeth, which may also occur in ITER with tungsten. Based on modeling, it is found that a reverse shear q-profile combined with a hollow pressure profile reduces the onset condition threshold, enabling helical core formation from an otherwise axisymmetric equilibrium.Large, spontaneous m/n = 1/1 helical cores are predicted in tokamaks with extended regions of low- or reversed-magnetic shear profiles in a region within the q = 1 surface and an onset condition determined by constant (dp/dρ)/Bt2 along the threshold. These 3D modes occurred frequently in Alcator C-Mod during ramp-up when slow current penetration results in a reversed shear q-profile. The onset and early development of a helical core in C-Mod were simulated using a new 3D time-dependent equilibrium reconstruction, based on the ideal MHD equilibrium code VMEC. The reconstruction used the experimental density, temperature, and soft-X-ray fluctuations. The pressure profile can become hollow due to an inverted, hollow electron temperature profile caused by molybdenum radiation in the plasma core during the current ramp-up phase before the onset of sawteeth, which may also occur in ITER with tungsten. Based on modeling, it is found that a reverse shear q-profile combined with a hollow pressure profile reduces ...


Importance
Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders.

Objective
To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum.

Data Sources
The PubMed, Embase, and PsycINFO databases were searched from inception to November 16, 2021. A hand search of reference lists of relevant articles was also performed.

Study Selection
Key study inclusion criteria in this meta-analysis were as follows: adult human study population, measurement of any marker of DNA or RNA damage from oxidative stress, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) with a control group or (2) prospective intervention. Two authors screened the studies, and 2 senior authors read the relevant articles in full and assessed them for eligibility.

Data Extraction and Synthesis
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two authors performed data extraction independently, and a senior coauthor was consulted in cases of disagreement. Data were synthesized with random-effects and multilevel meta-analyses.

Main Outcomes and Measures
The predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels. The main outcome was the standardized mean differences (SMDs) among patients and controls in nucleic acid oxidation markers compared across diagnostic groups. Analyses were divided into combinations of biological matrices and nucleic acids.

Results
Eighty-two studies fulfilled the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Overall, the data showed that patients with psychiatric disorders had higher NA-OXS levels vs controls across matrices and molecules. Pooled effect sizes ranged from moderate for urinary DNA markers (SMD = 0.44 [95% CI, 0.20-0.68]; P < .001) to very large for blood cell DNA markers (SMD = 1.12 [95% CI, 0.69-1.55; P < .001). Higher NA-OXS levels were observed among patients with dementias followed by psychotic and bipolar disorders. Sensitivity analyses excluding low-quality studies did not materially alter the results. Intervention studies were few and too heterogenous for meaningful meta-analysis.

Conclusions and Relevance
The results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum. NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.


Honey is an ancient remedy with a high potency against drug-resistant bacteria, which has gained renewed interest in naturopathic medicine for its beneficial effect in treatment and prevention of wound infections. The exact antibacterial property and mode of action of honey is still unknown, however in recent years, there has been various studies focusing on the effect of honey on bacterial gene regulation. With the focus of current literature being at the molecular level, the first aim of this study was to examine the effect of honey at the cell level and its influence on the metabolism of P. aeruginosa biofilm. The second objective of this study was to test the influence of the combination of the iron chelating agent (EDTA) and honey on biofilm metabolism. P. aeruginosa metabolism in this study was analyzed through (i) siderophore excretion and (ii) monitoring of the biofilm CO2 respiration rate with a Carbon dioxide Evolution Measurement System (CEMS). The results obtained indicate that honey reduces biofilm metabolism and inhibits siderophore production, while the combination of honey and EDTA has a greater impact on biofilm metabolism, which influences P. aeruginosa iron homeostasis, inhibits siderophore production, and increases bacterial recovery time after exposure. However, when provided at concentrations lower than its inhibitory concentration, honey is used as a nutrient source for biofilm development. The results obtained illustrated the importance of the environmental conditions on biofilm metabolism, as the biofilm response varied with minor changes in the composition of their media. In summary, this study showed that biofilm cells shut down their metabolism in the presence of honey, which also inhibits bacterial siderophore production and can play an importance role on the virulence of P. aeruginosa.


Weather data is a critical element in the decision making process for a vast number of entities and its timely and accurate portrayal is essential. The U.S. National Weather Service has utilized a combination of Open Source projects including: OpenLayers, Qooxdoo, PostGIS and Flot among others to create a mash-up called the Enhanced Data Display or EDD (preview.weather.gov/edd) to promote the development of a Weather Ready Nation. The EDD provides a platform to quickly communicate past, current and future weather conditions. What happens over the next couple of hours to a week dictates the agenda of everything from strategic resource placement to what to wear to work. More often than not, the weather forecast is not binary - there is always some probabilistic component that results from the inherent chaos of a 4-D fluid wrapped around a spinning sphere. Luckily, the EDD makes use of a variety of techniques that leverage Open Source technologies to present forecasts in both deterministic and probabilistic forms. The EDD contains many visual displays that refine bulky meteorological datasets into palatable forms. Whether you are looking to see what hazards you may face along a travel route or trying to find a heat map of how many people will be impacted by a tornado warning, the EDD can display this quickly. Finally, the ability to combine EDD layers with your own data makes this an extremely powerful application. EDD is a good example of how leveraging Open Source resources can result in an exquisite product.


In this paper, we explore the use of graph-based transforms to capture correlation in light fields. We consider a scheme in which view synthesis is used as a first step to exploit inter-view correlation. Local graph-based transforms (GT) are then considered for energy compaction of the residue signals. The structure of the local graphs is derived from a coherent super-pixel over-segmentation of the different views. The GT is computed and applied in a separable manner with a first spatial unweighted transform followed by an inter-view GT. For the inter-view GT, both unweighted and weighted GT have been considered. The use of separable instead of non separable transforms allows us to limit the complexity inherent to the computation of the basis functions. A dedicated simple coding scheme is then described for the proposed GT based light field decomposition. Experimental results show a significant improvement with our method compared to the CNN view synthesis method and to the HEVC direct coding of the light field views.


The responsiveness verification of a given communication protocol is to check whether the given protocol can recover from any abnormal state to a normal state within a permissible time or not. In order to make practical discussions, we assume that the lower and upper bounds of execution time are given for each message transfer and event. We propose a new responsiveness verification method which executes several events concurrently based on residual times of events, and develop a simulator which implements the proposed method. Then we present an experience which applies the simulator to the design of an actual connection establishment protocol for a certain plant control system. The system adopts the client server model and real time constraints exist on connection establishments. In the experience, we first specify the protocol straightforwardly. Then we apply the simulator to the specification and detect design faults against responsiveness. Next, we revise the specification successfully based on the state sequences generated by the simulator. The results of the experience conclude that the proposed method is effective for the case study.


The Internet of Things (IoT) is being deployed in an ever-growing range of applications, from industrial monitoring to smart buildings to wearable devices. Each of these applications has specific computational requirements arising from their networking, system security, and edge analytics functionality. This diversity in requirements motivates the need for adaptable end-devices, which can be re-configured and re-used throughout their lifetime to handle computation-intensive tasks without sacrificing battery lifetime. To tackle this problem, this article presents Chimera, a low-power platform for research and experimentation with reconfigurable hardware for the IoT end-devices. Chimera achieves flexibility and re-usability through an architecture based on a Flash Field Programmable Gate Array (FPGA) with a reconfigurable software stack that enables over-the-air hardware and software evolution at runtime. This adaptability enables low-cost hardware/software upgrades on the end-devices and an increased ability to handle computationally-intensive tasks. This article describes the design of the Chimera hardware platform and software stack, evaluates it through three application scenarios, and reviews the factors that have thus far prevented FPGAs from being utilized in IoT end-devices.


Accuracy of the prediction o f the dynamic response of deepwater fixed offshore platforms to irregular sea waves depends very much on the theory used to determine wave kinematics. A common industry practice consists of using linear wave theory, which assumes infinitesimal wave steepness, in conjunction with empirical wave stretching techniques to provide a more realistic representation of near-surface water kinematics. The current velocity field is then added to the wave-induced fluid velocity field and the wave-and-current forces acting on the structure are computed via Morison's equation. The first objective o f this study is to compare the predicted responses o f Cognac, a deepwater fixed platform, obtained from several popular empirical wave models with the response Cognac predicted based on the hybrid wave model. The latter is a recently developed higher-order, and therefore more accurate, wave model which satisfies, up to the second-order in wave steepness, the local mass conservation and the linear free surface boundary conditions at the instantaneous wave surface. The second objective of this study is to correlate the various analytical response predictions with the measured response of Cognac. Availability of a set of oceanographic and structural vibration data for Cognac provides a unique opportunity to evaluate the prediction ability o f traditional analytical models used in designing such structures. The results of this study indicate that (i) the use of the hybrid wave model provides predicted platform response time histories which overall are in better agreement with the measured response than the predictions based on the various stretched linear wave models; and (ii) the Wheeler stretching technique produces platform response time histories which overall are more accurate than those obtained by using the other stretching schemes considered here.


Changes of the oxygen consumption and the main parameters of the blood respiratory function as well as oxygen transport, were studied in Wistar rats under conditions of immersion hypothermia (with rectal temperature 15-13 degrees C). From the viewpoint of the oxygen exchange, the rectal temperature 20 degrees C was found to be the critical level of the hypothermia.


The Go game is ancient very complex game with simple rules which still is a challenge for the AI.This work cover some neuroevolution techniques used in reinforcement learning applied to the GO game as SANE (Symbiotic Adaptive Neuro-Evolution) and presents a variation to this method with the intention of evolving better strategies in the game. The computer Go player based in SANE is evolved againts a knowed player which creates some problem as determinism for which is proposed the co-evolution. Finally, it is introduced an algorithm to co-evolve two populations of neurons to evolve better computer Go players.


Abstract:
 Fungi of woody debris are a diverse and functionally important component of forest ecosystems, but are potentially threatened by forest management activities. We used fruiting body and molecular sampling of the nrLSU gene to compare the composition and richness of fungal communities between 2 decay classes of conifer logs (classes 1 and 4) and among boreal mixedwood sites from 3 management histories (mechanized clearcutting, horse-based clearcutting, and unlogged). In 5 sites per management type, 5 logs per decay class were sampled for fruiting bodies. Wood samples for DNA extraction were collected from the logs at 3 mechanized logged and 3 unlogged forest sites. Fruiting body surveys yielded 116 species; 34 from decay class 1 logs, 65 from decay class 4 logs, and 17 from both. Molecular sampling, based on selection of 20 clones per log, yielded 304 operational taxonomic units (OTUs); 97 from decay class 1 logs, 184 from decay class 4 logs, and 23 from both. Community composition differed strongly between the 2 decay classes both for the fruiting body and OTU samples, with more species being recovered from decay class 4 than decay class 1 logs. Community composition also significantly varied according to log diameter and volume for fruiting bodies. The number of fruiting bodies on decay class1 logs was significantly greater in unlogged than logged sites and also was positively correlated with site-level volume of recently-decayed conifer woody debris. Dacrymyces chrysospermus and Fomitopsis rosea were significantly more frequently encountered in unlogged than logged stands. Despite relatively large volumes of woody debris in the logged stands that we sampled, we obtained evidence that logging in these forests resulted some 30–60 years later in a reduction in the amount and diameter of early-decay coniferous downed wood, with reductions in fungal fruiting body diversity as a result.


Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. Most proteins function in collaboration with other proteins and one goal of proteomics is to identify which proteins interact. This is especially useful in determining potential partners in cell signaling cascades. A number of techniques have been developed for the identification and classification of protein-protein interactions. The techniques developed in past years are still far from perfect. The Jordan neural network classification model tries to overcome this problem. The Jordan Neural Network takes amino acid composition of protein pairs to classify them interacting and non-interacting. Jordan neural network classification model outperforms the other methods for protein-protein interaction classification. Jordan neural network classification model proves to be better model with higher accuracy along with improved specificity and sensitivity than the various existing techniques.


In the auditory cortex, synaptic inhibition is known to be involved in shaping receptive fields, enhancing temporal precision, and regulating gain. Cortical inhibition is provided by local GABAergic interneurons, which comprise 10–20% of the cortical population and can be separated into numerous subclasses. The morphological and physiological diversity of interneurons suggests that these different subclasses have unique roles in sound processing; however, these roles are yet unknown. Understanding the receptive field properties of distinct inhibitory cell types will be critical to elucidating their computational function in cortical circuits. Here we characterized the tuning and response properties of parvalbumin-positive (PV+) interneurons, the largest inhibitory subclass. We used channelrhodopsin-2 (ChR2) as an optogenetic tag to identify PV+ and PV− neurons in vivo in transgenic mice. In contrast to PV+ neurons in mouse visual cortex, which are broadly tuned for orientation, we found that auditory cortical PV+ neurons were well tuned for frequency, although very tightly tuned PV+ cells were uncommon. This suggests that PV+ neurons play a minor role in shaping frequency tuning, and is consistent with the idea that PV+ neurons nonselectively pool input from the local network. PV+ interneurons had shallower response gain and were less intensity-tuned than PV− neurons, suggesting that PV+ neurons provide dynamic gain control and shape intensity tuning in auditory cortex. PV+ neurons also had markedly faster response latencies than PV− neurons, consistent with a computational role in enhancing the temporal precision of cortical responses.


Nutritional status of men, aged 50, which is considered as a high risk group for noncommunicable heart diseases was investigated. The study showed that the chemical composition of diet could be considered as a risk factor for cardiovascular diseases. This diet is too rich in simple sugars and fats, especially of animal origin, and poor in complex sugars and antioxidants.


This year the world-famous taxonomist-zooplanktonologist A. A. Shmeleva has celebrated the 90ᵗʰ anniversary. A significant contribution in the study of the Mediterranean and the World ocean zooplankton was made by A. A. Shmeleva. She has registered about 100 species of copepods not mentioned in Mediterranean before; she has found and described more then 40 species of copepods that are new for science. These discoveries as well as taxonomic description of two genus of copepods have made her one of the most famous experts on the taxonomy of copepods in the world. The scientific works by A. A. Shmeleva have become classics, and they don't lose their actuality in process of time.


The sight of a colourful border or the scent of a rose may excite the senses and provide the elusive "feelgood factor". In this text, journalist and broadcaster Don shows how to exploit the sensuous qualities of your garden to the full. Each sense is examined in turn, with an explanation of how it works and how the messages we receive from the garden affect our moods and emotions. He takes a sensuous journey through every part of the garden, from the soil itself, through plants and garden wildlife, to walls and surfaces and features such as pools and pergolas. The journey reveals how each season brings its own distinct sensations, from the fresh smells and colours of spring to the cold, stark beauty of winter. The descriptions of sensory experiences are accompanied by practical guidance for creating your own sensuous garden, with ideas for planning and design. Photographs bring the sights, scents, tastes and sounds of the sensuous garden to life, and a directory describes the characteristics and needs of 200 of the best plants for stimulating the senses.


Non-violence and truth are one of the most indomitable elements of the philosophy propounded by Mahatma Gandhi. It was the approach which was accepted as only logical approach to morality by Martin Luther King. Gandhi was a grand advocate of truth, non-violence and was very buoyant about their role in the lives of the masses in order to make the world a sustainable and harmonious place. According to Gandhi non-violence is the ultimate way to discover truth and this is for the same reason both of them are knotted in such a way it is practically impossible to disengage them. The paper, thus, encapsulates the hidden layers of the Gandhain philosophy called Satyagraha along with a live interview of Gandhi with Sir Chimanlal.


Hodgkin's lymphoma is believed to spread in an orderly fashion within the lymphatic compartment. In a minority of cases, after reaching the spleen, the neoplasm disseminates, reminiscent of metastasis. In the spleen, the Hodgkin-Reed-Sternberg tumor cells come across platelets in the blood vessels and mainly in the splenic red pulp. Based on this knowledge, we investigated the possibility of platelets inducing cell adhesion in Hodgkin's lymphoma cell lines. We showed that L428 and KMH-2 cells strongly adhere to thrombin-activated platelets. Cell adhesion to platelets is partially dependent on CD15 antigens (LewisX), mainly sialyl-CD15, and P-selectin. KMH-2, as compared to L428 cells, showed increased binding due to its differential high expression of the sialyl-CD15. As a consequence of incubation with platelets, KMH-2 cells also produced increased amounts of tumor necrosis factors α (TNFα) followed by enhanced binding to human vascular endothelial cells (HUVEC). Incubation of both cell lines with activated platelets also induced activation of AP-1 transcription complex. Our findings are consistent with the concept that platelets play a critical role in the dissemination of HRS cells in HL, predominantly in the spleen, by increasing cell adhesion and thus promoting their proliferative and migratory properties beyond the lymphatic system.


The present paper aims to shed lights on effect of optimum dietary level of Chlorella vulgaris powder (CP) as a feed additive on some blood biochemical parameters (Cholesterol (CHO), triglyceride (TG), total protein (TP), glucose (GLU), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lysozyme) and digestive enzymatic activities (amylase, lipase and protease) of the grey mullet (Mugil cephalus L). Four experimental diets were supplemented with CP at 0, 5, 10 and 15 g kg−1diet (CP0, CP, CP10 and CP15). Number of twelve tanks (60-L) with three replicates for treatment group (n=10 per tank with average initial weights 14.95 ± 2.01 g) and the control group were considered. After 60 days of the feeding trial, fish fed CP5 diet had lower serum CHO and TG levels than did fish fed CP0, CP10 and CP15 diets (P 0.05). The highest serum total protein, amylase, protease, lipase and lysozyme activities were observed in fish fed CP5. Also, fish fed CP10 and CP15 diets had higher digestive enzymatic activities, serum total protein and lysozyme activities than did fish fed CP0 (P<0.05). These results indicate that dietary supplementation of 5 g chlorella powder in the commercial diets could improve the blood chemical responses and the activity of digestive enzyme in grey mullet.


Abstract. Two hundred consecutive patients with femoral neck fractures (FNF) and 200 controls matched by age, sex, nursing home residency and number of admissions within the last 2 years, were interviewed about recent drug use. The matching criteria were chosen to achieve case and control groups that were comparable with regard to overall physical disability. Thus a preliminary study had shown FNF to be strongly associated with nursing home residency and to be correlated with the number of recent hospital admissions. FNF was found to be negatively associated with use of coronary drugs (OR = 0.27; 95% CI = 0.11‐0.70) and positively associated with drug use in general (OR = 2.00: 95% CI = 1.04‐3.05). The OR for the various classes of psychotropic drugs was consistently > 1., although this was not statistically significant. An inherent problem in interpreting such findings is that underlying disease may predispose the subject to both FNF and drug use, thus creating a non‐causal relationship.


This study constructs new understandings regarding the impact of the transformations that have taken place in the domestic environment of Saudi Arabia following the discovery of oil. While most previous research in this area has highlighted the loss of identity caused by this transformation, my research reveals how these developments have also resulted in new modes of cultural preservation in a domestic environment. It also explores the significant role of private museum making as a network of cultural practices that reflect and preserve Saudi culture for future generations.

Despite the high price of land for housing and construction materials, some individuals in Saudi society have invested their savings to collect and preserve traditional artefacts in private museums in their homes. Through analysis of a number of such examples in the Eastern Province, with an in-depth study of one, this research explores the relationship between cultural practice, cultural preservation and resilience, and interprets this from an architecture perspective. Framed by a set of key theoretical concepts (cultural trauma, cultural resilience and cultural preservation), this study aims to highlight the positive cultural adaptation of domestic environments after the rapid transformation brought about by the discovery of oil. An in-depth qualitative case study provides an example of how a resident transformed an imported, villa style residence to reflect her identity, religion, culture, and past experience and how, through a practice of museum making in her home, not only translated her memories, identity, tangible and intangible heritage into a museum, but also gave herself new agency in public life. This research offers fresh perspective and insight into the role of women as social influencers and explores their creative ability in cultural preservation.

These findings fill a knowledge gap in the study of home interiors and cultural preservation, explained with reference to two intersecting perspectives: the transformation of the national discourse on heritage and the transformation of the role of women on Saudi society. It also shows evidence of the shift that occurred from the oil boom in 1938 to the museum boom in 2014. This research explores and identifies the Private Museum Movement (PMM), defining it as: an individual's attempt to preserve Saudi cultural heritage through the practice of museum-making within their private home.


At present, there is no common perception in modern science and international political practice of what the world (international) order (legal order) is. The article analyzes the relevant points of view. It is concluded that by referring to the relevant provisions, generally accepted in the framework of the general theory of law and the theory of international law, it is possible to get close enough to the solution of this problem. The article also examines other problems related to the essence of the concepts of the world (international) order and its types (world public order, world legal order and global world legal order), and also the varieties of social norms of the international regulatory system, the results of the implementation of which shape the corresponding orders. Special attention is paid to the fact that, in contrast to the widespread perceptions, all three types of world order are neither a set of international relations, nor a set of norms regulating such relations. According to the theory of international law, they are the result of the implementation of the requirements of certain norms of the international regulatory system aimed at managing international public relations. In addition, various factors influence the state of a particular type of international order (including a change in the hierarchy of states depending on their role in the international political and/or economic system, the formation of new centers of power, a change in bipolarity, polycentricity or monocentricity of the world, the emergence of multilateral integration formations, the activities of international multilateral institutions, etc.), but they should also not be confused with international orders themselves.


Building on the concept of 'impact literacy' established in a previous paper from Bayley and Phipps, here we extend the principles of impact literacy in light of further insights into sector practice. More specifically, we focus on three additions needed in response to the sector-wide growth of impact: (1) differential levels of impact literacy; (2) institutional impact literacy and environment for impact; and (3) issues of ethics and values in research impact. This paper invites the sector to consider the relevance of all dimensions in establishing, maintaining and strengthening impact within the research landscape. We explore implications for individual professional development, institutional capacity building and ethical collaboration to maximise societal benefit.


Introduction: Achondroplasia is the most common reason for disproportionate short stature. Normally, orthopedic limb lengthening procedures must be discussed in the course of this genetic disorder and have been successful in numerous achondroplastic patients in the past. In some cases, the disease may lead to leg length differences with need for surgical correction. Case Report: We report a case of achondroplastic dysplastic coxarthrosis with symptomatic leg length difference after bilateral total hip arthroplasty in a 52-year-old female patient, in which a distal femoral shortening osteotomy was successfully performed. Conclusion: Femoral shortening osteotomy is very uncommon in patients with achondroplasia. We conclude, however, that in rare cases it can be indicated and provide the advantage of shorter operation time, less perioperative complications and faster recovery compared to leg lengthening procedures.


A luminescent light source (1) is configured to include: a substrate (10); a terminal (11) and a land (12) formed on the substrate (10); a light-emitting element (14) mounted on the land (12) via a bump (13); and a phosphor layer (15) that covers the light-emitting element (14) and is filled in an interstice between a principal surface of the substrate (10) and the light-emitting element (14), wherein the phosphor layer (15) contains a phosphor and a light-transmitting base material, and a content by volume of the phosphor in a part (15a) of the phosphor layer (15) filled in the interstice and a content by volume of the phosphor in a part (15b) of the phosphor layer (15) covering the light-emitting element (14) are substantially equal to each other.


The Blue Gene®/L compute chip is a dual-processor system-on-a-chip capable of delivering an arithmetic peak performance of 5.6 gigaflops. To match the memory speed to the high compute performance, the system implements an aggressive three-level on-chip cache hierarchy. The implemented hierarchy offers high bandwidth and integrated prefetching on cache hierarchy levels 2 and 3 (L2 and L3) to reduce memory access time. A Gigabit Ethernet interface driven by direct memory access (DMA) is integrated in the cache hierarchy, requiring only an external physical link layer chip to connect to the media. The integrated L3 cache stores a total of 4 MB of data, using multibank embedded dynamic random access memory (DRAM). The 1,024-bit-wide data port of the embedded DRAM provides 22.4 GB/s bandwidth to serve the speculative prefetching demands of the two processor cores and the Gigabit Ethernet DMA engine. To reduce hardware overhead due to cache coherence intervention requests, memory coherence is maintained by software. This is particularly efficient for regular highly parallel applications with partitionable working sets. The system further integrates an on-chip double-data-rate (DDR) DRAM controller for direct attachment of main memory modules to optimize overall memory performance and cost. For booting the system and low-latency interprocessor communication and synchronization, a 16-KB static random access memory (SRAM) and hardware locks have been added to the design.


Purpose
This paper aims to focus on the effects of human capital composition, innovation portfolio and size on manufacturing firms' performance. Moreover, it seeks to empirically identify the levels of education that are significant in labour productivity.

Design/methodology/approach
The resource-based view (RBV) theory is applied using data gathered from the National Innovation Survey in the Manufacturing Industries of Peru. Using the ordinary least squares method on a sample of 584 Peruvian manufacturing firms, the effects on firm performance of two subsamples according to innovation portfolio and firm size are determined.

Findings
The direct effects of human capital composition on productivity show that the higher the workers' educational level, the higher the productivity. However, if this relationship is analysed in terms of the innovation portfolio, the authors find that labour productivity in companies with product–service innovation is greater (i.e. more significant) than in traditional manufacturing firms with only product innovations. Similarly, if this relationship is compared in terms of company, the authors find that large companies are more significant than small and medium-sized enterprises.

Practical implications
The study furthers the understanding of how the relationship between human capital composition, innovation portfolio and size of manufacturing firms positively affects labour productivity. Hence, it can help managers to craft their innovation portfolio according to the educational level of their human capital. This could require that not only human resource management innovates, but also that strategic partnerships be developed with educational establishments to boost training towards product–service innovation.

Originality/value
This study's results provide confirmation that the configuration of human resources, innovation portfolio and size plays a significant role on manufacturing firms' performance, particularly in the context of developing countries.


Further evidence for the role of enterotoxigenic Escherichia coli as an etiologic agent of diarrhea is presented. A retrospective study of 71 cases of diarrhea in Mexican children demonstrated that greater than 40% of them harbored E. coli that produced heat-labile and/or heat-stable enterotoxin. The antigenic surface-associated colonization factor of E. coli strain H-10407 has been further characterized: this pilus-like antigen is produced under conditions of growth that repress the production of common pili of E. coli. The E. coli H-10407-type colonization factor pilus has been identified as one of the antigens possessed by a strain of E. coli that produced only heat-stable enterotoxin and that was responsible for an outbreak of pediatric diarrhea.


Patients with non‐alcoholic fatty liver disease have unhealthy diets, sedentary behaviour and not enough physical activity. This lifestyle triggers liver disease and probably favours its progression. It also has significant deleterious effects on health and longevity and should therefore be corrected by first‐line therapy at all stages of the disease. However, important questions remain: is weight loss alone beneficial or do particular diets have beneficial effects beyond weight loss? Which specific micro‐ or macronutrients are clearly harmful? Does exercise without weight loss improve hepatic histology and what type of exercise is optimal? Does moderate or only vigorous exercise have metabolic and hepatic benefits? What is the efficacy of lifestyle measures outside of clinical trials? And most importantly, what is the turning point in the natural history of liver disease when non‐pharmacological measures should be combined with drug therapy?


We propose the \emph{Target Charging Technique} (TCT), a unified privacy analysis framework for interactive settings where a sensitive dataset is accessed multiple times using differentially private algorithms. Unlike traditional composition, where privacy guarantees deteriorate quickly with the number of accesses, TCT allows computations that don't hit a specified \emph{target}, often the vast majority, to be essentially free (while incurring instead a small overhead on those that do hit their targets). TCT generalizes tools such as the sparse vector technique and top-$k$ selection from private candidates and extends their remarkable privacy enhancement benefits from noisy Lipschitz functions to general private algorithms.


We are facing promising developments in the area of mobile services where context-aware systems can take the location and position of a user, her preferences and 'smart' objects into account, adding (implicit) interaction between a mobile device (of the user) and the real world. The assimilation of ubiquitous computing by education marks an important step forward, as being pervasive and persistent it allows students to access education calmly, flexibly, and seamlessly. This paper focus on a framework proposal with a well contained and defined application goal in Ubiquitous Computing and a prototype directed for Ubiquitous Learning environments. This system can augment physical objects in an educational environment with additional multimedia information, which is displayed in public shared displays according to the user (student or teacher) that faces the system. The information is contextual, based not only in the object, but also in its specific location, in the environment and in the detected user profile. A generic architecture was designed to help on the implementation of this augmented objects framework in any physical space.


Spongiform leukoencephalopathy is a distinct pathological entity usually following inhalation of heroin, while spongiform leukoencephalopathy resulting from intravenous injection of heroin is very rare. The magnetic resonance imaging findings are non-specific with widespread symmetrical high-signal lesions in white matter. This report is of an intravenous heroin addict who presented with clinical features of encephalopathy with restricted diffusion on diffusion-weighted imaging. Diffusion-weighted imaging distinguished this drug-induced encephalopathy from other types of leukoencephalopathy. This is the third case report of spongiform leukocenpahalopathy showing restricted diffusion on diffusion-weighted imaging in the English literature.


From the 1960s onwards, the clothing industry in the Netherlands and elsewhere in the European Union, experienced a deep crisis. Numerous went bankrupt and, even more so, workers lost their jobs. Imports from low wage countries started providing the bulk of retailers' collections. In the high wage economy of the Netherlands there seemed to be no more room for labour intensive industry such as clothing. However, in the 1980s a surprising development took place. In Amsterdam, a substantial number of new small clothing firms were established, focusing on short-cycle fashion production. Most of these firms were run by Turkish immigrants. During the 1990s, most of these firms disappeared again. At the same time the pattern of imports changed as well, with nearby countries in the Mediterranean region and Eastern Europe increasing their share of the fashionable clothing market. Migration and fashion played an important role in these processes. In this study, Stephan Raes analyses these developments and tries to explain why they occurred. He offers an elaborate multilevel theoretical framework to deal with the changes in the spatial organization of clothing supply. His analysis shows how large retailers have become the most powerful players in the Dutch clothing sector, and how the changes in the spatial pattern of clothing supply have to be understood against the changing logistics of their sourcing. The study takes us from the history of the Dutch clothing industry in the 19th century, to the detailed description of migrants entrepreneurs in the sector, and the changes in trade patterns. It focuses on the interaction of retailers with other actors in the sector, such as suppliers, consumers and governments. Finally, it takes places these developments against the background of transformations in the political economy of the Netherlands and Turkey.


ObjectivePyruvate has been shown to be protective in numerous in vitro and in vivo models of oxidant-mediated cellular or organ system injury. Unfortunately, the usefulness of pyruvate as a therapeutic agent is abrogated by its very poor stability in solution. In an effort to take advantage of the ability of pyruvate to scavenge reactive oxygen species while avoiding the problems associated with the instability of pyruvate in solution, we sought to determine whether a simple derivative, ethyl pyruvate, would be protective in an animal model of reactive oxygen species-mediated tissue injury, namely mesenteric ischemia and reperfusion in rats. DesignProspective, randomized trial. SettingAnimal research center. SubjectsMale Sprague-Dawley rats. InterventionsUnder general anesthesia, rats were subjected to 60 mins of mesenteric ischemia followed by 60 mins of reperfusion. Controls (n = 6) received intravenous lactated Ringer's solution according this dosing schedule: 1.5 mL/kg bolus before ischemia, 3.0 mL/kg bolus before resuscitation, and 1.5 mL·kg−1·hr−1 by continuous infusion. Two experimental groups received similar volumes of either pyruvate (n = 6 each) or ethyl pyruvate (n = 9) solution made up exactly like lactated Ringer's solution except for the substitution of eitherpyruvate or ethyl pyruvate for lactate, respectively. Measurements and Main Results To obtain tissues for assessing mucosal permeability and histology, five 10-cm long segments of small intestine were obtained at the following time points: baseline, after 30 and 60 mins of ischemia, and after 30 and 60 mins of reperfusion. Mucosal permeability to fluorescein isothiocyanate dextran (molecular weight 4000 Da) was assessed ex vivo by using an everted gut sac method. Compared with controls, treatment of rats with either pyruvate solution or ethyl pyruvate solution significantly ameliorated the development of intestinal mucosal hyperpermeability during the reperfusion. Treatment with ethyl pyruvate solution also significantly decreased the extent of histologic mucosal damage after mesenteric reperfusion. ConclusionsTreatment with Ringer's ethyl pyruvate solution ameliorated structural and functional damage to the intestinal mucosa in a rat model of mesenteric ischemia/reperfusion. Ethyl pyruvate solution warrants further evaluation as a novel therapeutic agent for preventing oxidant-mediated injury in various disease states.


This paper draws its conclusions from a multidisciplinary study of the refugee determination process in Canada, the aim of which was to examine the strengths and weaknesses of the system and to explore means of improving it through an in-depth analysis of the diversity of attitudes and perceptions of different actors involved in the process. The basic hypothesis is that the legitimacy of the action of the Immigration and Refugee Board (hereafter IRB) is challenged because of a series of disagreements on the way it operates. Using interviews with former Board members, as well as with other professional actors of the system (lawyers, NGO workers, interpreters, health professionals), we try to understand better the parameters of the problems facing the IRB on three sets of issues: the appointment and renewal of Board members; the relationships between Board members within the IRB; the evaluation of the evidence by Board members. All issues relate mainly to the principles of independence and impartiality of the IRB, as an expert administrative tribunal. In particular, using the idea of 'critical space' as a conceptual framework, this study tries to ascertain more precisely how critical spaces within the IRB were being used in order to foster a common culture of independence and impartiality within the institution, or not. This study covers the period 1989-2002: it signals reforms accomplished since and suggests more means for improvement.


The use of ontologies and taxonomies contributes by providing means to define concepts, minimize the ambiguity, improve the interoperability and manage knowledge of the security domain. Thus, this paper presents a literature survey on ontologies and taxonomies concerning the Security Assessment domain. We carried out it to uncover initiatives that aim at formalizing concepts from the Information Security and Test and Assessment fields of research. We applied a systematic review approach in seven scientific databases. 138 papers were identified and divided into categories according to their main contributions, namely: Ontology, Taxonomy and Survey. Based on their contents, we selected 47 papers on ontologies, 22 papers on taxonomies, and 11 papers on surveys. A taxonomy has been devised to be used in the evaluation of the papers. Summaries, tables, and a preliminary analysis of the selected works are presented. Our main contributions are: 1) an updated literature review, describing key characteristics, results, research issues, and application domains of the papers; and 2) the taxonomy for the evaluation process. We have also detected gaps in the Security Assessment literature that could be the subject of further studies in the field. This work is meant to be useful for security researchers who wish to adopt a formal approach in their methods and techniques.


Aim: The main objective of the current investigation was to develop and evaluate the microemulsion based transdermal gel for isradipine, poorly water soluble and low bioavailable drug. Materials and Methods: Saturation solubility studies of the drug were conducted in various solvents and oils. Oleic acid, Tween 80 and Transcutol P were selected as oil phase, surfactant and cosurfactants, respectively, as the drug was having highest solubility in these solvents. The pseudo-ternary phase diagrams were constructed using water titration method by varying surfactant to the co-surfactant (Smix) ratio as 1:1, 1:2, 1:3, 2:1, and 3:1. Microemulsion formulations ratios were selected from the constructed pseudo-ternary phase diagrams. Results and Discussion: Microemulsion prepared with oil to Smix ratio of 1:9 (F9) was found to be stable with the globule size of 50.4 ± 3.54, and has more % of drug diffusion of 88.4 ± 1.9% within 6 h and has been selected for the preparation of microemulsion based gel (MEBG) using carbopol 934 as gelling agent. The prepared gel has shown 96.74 ± 2.8% drug releases in 8 h which was higher than control gel. In vivo pharmacokinetic studies conducted in rabbits revealed that the bioavailability of MEBG was increased 5.4 times compared to oral suspension. Conclusion: This demonstrates avoidance of first pass metabolism and oral degradation and indicates the effective management of plasma profile of isradipine when it is administered as MEBG through transdermal route.


In their recent article, Takahashi et al. (1) suggest that heatinduced DNA double strand breaks contribute to heat-induced cell killing because heat treatment induces histone gH2AX-containing foci. Such foci have been associated with double strand breaks induced by ionizing radiation, other agents, and other stresses (2). However, the authors disregard the hyperthermia biology literature, which indicates that heat-induced DNA damage is not involved in heat killing. Heat probably does not induce DNA damage directly. The authors point out, however, that heat may induce DNA base damage indirectly via protein damage (1). For repair of ionizing radiation–induced base damage, it is thought that heat inhibits the excision step without impairing the incision step (3). For clustered base damage, such imbalance in incision and excision may result in conversion of base damage into DNA double strand breaks (3). By analogy, the authors speculate that heat-induced base damage may be converted into double strand breaks. However, the levels of base damage do not correlate with the extent of heat-induced cell killing (4). Moreover, although data using the neutral comet assay is presented (1), the use of a variety of sensitive biochemical and biophysical approaches that are more double strand break specific than the comet assay have failed to detect double strand breaks after heat (3). Moreover, Mre11, a protein directly involved double strand break repair that also forms foci immediately after ionizing radiation (5), is not found in foci after heat shock; rather, Mre11 exits from the nucleus after heat shock (6). This clearly shows that the gH2AX foci seen after heat shock are completely different from those seen after ionizing radiation and cannot be taken as evidence for heat-induced double strand break. Several other observations are also inconsistent with the notion that DNA damage is involved in heat-induced killing. Incorporation of BrdUrd into DNA, known to destabilize DNA and to enhance radiosensitivity, does not enhance heat killing. The potential lethal damage response associated with the ability to repair ionizing radiation–induced DNA damage has not been found for hyperthermia. Finally, if heat shock would induce DNA double strand breaks, either directly or indirectly, chromosomal aberrations, associated with the ionizing radiation–induced DNA double strand breaks, would be expected to occur also in cells heated in various phases of the cell cycle, which is not the case (3). The authors nevertheless state that a DNA double strand break repair–deficient cell line is also heat sensitive, arguing in favor of a role for double strand break in heat killing (1). However, a literature survey on 30 different mouse cell lines reveals no general correlation between heat sensitivity and radiosensitivity (Fig. 1A). Because the authors suggest that double strand break only partially determine heat killing, one could still explain the latter by assuming cell line–dependent differences in the sensitivity of other targets of heat (i.e., protein damage) that would mask this correlation. Therefore, we also analyzed data from the literature describing a number isogenic panels of radiosensitive cells deficient in DNA double strand break repair and their normal counterparts for their heat sensitivity. It is highly unlikely that DNA repair gene–complemented cell lines would simultaneously acquire an altered capacity to repair protein damage (the presumed main cause of heat-induced cell death). Thus, if heat would indeed induce DNA double strand breaks relevant to its toxicity, then this should be revealed in such pairs. However, as can be seen in Fig. 1B , there is no relation between double strand break repair deficiency and heat sensitivity in these isogenic panels. Thus, on the basis of these data, one must conclude that even if double strand breaks are induced by heat, they do not contribute to heatinduced killing. It is now known that gH2AX-containing foci can also be induced by other non–double strand breaks–inducing treatments, such as treatment with the methylating agent N-methyl-NV-nitro-N-nitrosoguanidine (7) or exposure to hypertonic buffers (8), showing that the gH2AX phosphorylation and foci formation is a general stress response, e.g., to changes in the chromatin (2), rather than to double strand breaks only. Heat is also known to induce major alterations in chromatin structure, not by inducing DNA damage but as a consequence of heat-induced protein denaturation or aggregation (3). In fact, the new and interesting observations by I2005 American Association for Cancer Research. doi:10.1158/1078-0432.CAN-05-0006 Figure 1. Absence of a correlation between radiation sensitivity and heat sensitivity. A, a cross-correlation of radiation sensitivity (expressed as the dose of X-ray required to kill 90% of the cells) with heat sensitivity (expressed as the equivalent time of heating at 44jC required to kill 90% of the cells) in 30 different mouse cell lines derived from the literature. B, comparison of heat sensitivity between various radiosensitive mutants (deficient in either nonhomologous end joining or in homologous recombination) and their isogenic repair–proficient counterparts. The average sensitivity of the groups (points with bars ) is not different; there is also no trend for increase or decrease in heat sensitivity in matched panels (lines ).