Advanced neuroimaging provides new opportunities to enhance head injury models, including the incorporation of white matter (WM) structural anisotropy. Information from high-resolution neuroimaging, however, usually has to be "down-sampled" to match a typically coarse brain mesh. To understand how this mesh-image resolution mismatch affects impact simulation and subsequent response sampling, we compared three competing anisotropy implementations (using either voxels, tractography, or a multiscale submodeling) and two response sampling strategies (element-wise or tractography-based, using brain mesh or neuroimaging for region segmentation, respectively). Using the combination of high resolution options as a baseline, we studied how the choice in each individual category affected the resulting injury metrics. By simulating a recorded loss of consciousness head impact, we found that injury metrics including peak strain and injury susceptibility in the deep WM regions based on fiber strain, but not on maximum principal strain, were sensitive to the anisotropy implementation, response sampling, and region segmentation. Overall, it was recommended to use tractography for anisotropy implementation and response sampling, and to employ neuroimaging for region segmentation, because they led to more accurate injury metrics. Further refining mesh locally via submodeling was unnecessary. Brain strain responses were also parametrically found to be closer to that from minimum fiber reinforcement, consistent with the fact that the majority of WM had a rather high degree of fiber dispersion. Finally, the upgraded Worcester Head Injury Model incorporating WM anisotropy was successfully re-validated against cadaveric impacts and an in vivo head rotation ("good" to "excellent" validation with an average Correlation Analysis score of 0.437 and 0.509, respectively). These investigations may facilitate further continual development of head injury models to better study traumatic brain injury.


We report the results of an experiment designed to examine investment project selection under promotion incentives, modeled as tournament contracts. For a given expected return, the owner prefers investments with lower systematic risk. Therefore, to the extent managers select investments other than those yielding the highest risk-adjusted rates of return, they diverge from what the owner desires. In the presence of promotion incentives, we identify a situation in which the maximization of expected compensation by managers is incompatible with their selection of investment projects that maximize the risk-adjusted rate of return. The results indicated that subjects recognize the strategic implications of alternative promotion scenarios and respond to them in an opportunistic fashion.


Circulating cell-free DNA (cfDNA) has been implicated as an important biomarker and has been intensively studied for "liquid biopsy" applications in cancer diagnostics. Owing to its small fragment size and its low concentration in circulation, cfDNA extraction and purification from serum samples are complicated, and the extraction yield affects the precision of subsequent molecular diagnostic tests. Here, we report a novel approach using nitrogen-mustard-coated DNA capture beads (NMD beads) that covalently capture DNA and allow direct subsequent polymerase chain reaction (PCR) amplification from the NMD bead without elusion. The complex DNA extraction and purification processes are not required. To illustrate the diagnostic use of the NMD beads, we detected short DNA fragments (142 bp) that were spiked into fetal bovine serum (as a model serum sample). The spiked DNAs were captured directly from serum samples and detected using real-time PCR at concentrations as low as 10 fg/mL. We anticipate that this DNA capture bead technique has the potential to simplify the preanalytical processes required for cfDNA detection, which could significantly expand the diagnostic applications of liquid biopsy.


The kinetic typography animates the static text and it will enable the delivery the opinion and emotion, but we should use professional software or do complex coding precess to create a motion into an existing static text. In this paper, we propose the primitive motion API which is the way to configure the kinetic typography easily by adding a motion into the static text. In the pursuit of this purpose, we analyzed the movement of the text, defined the underlying levels of the movement and designed the primitive motion API to express the kinetic typography promptly. Furthermore, we verified the performance of the primitive motion API by testing the usability. Using the primitive motion API to implement the kinetic typography explicitly might substitute for tedious coding process and usage of the existing professional software so it makes anyone be able to apply the kinetic typography in a variety of applications.


Advances in digital computers have been spectacular but increasingly complex to model. Even the cycle-accurate simulators, which are costly to develop and run have questionable accuracy. This thesis provides a simple, accurate, scientifically proven, and analytic model to accurately predict the performance of real applications. The method creates two profiles as a function of time or problem sizes. The first profile, Hardware Signature, that reveals computer hardware speed, is obtained by running a universal benchmark, HINT or by running an analytical model, AHINT. The second profile, Application Signature (APPMAP), that divulges intrinsic application requirements, can be obtained by four different methods outlined in the thesis. The convolution of these two profiles are used to predict real application performance. The model was tested using 25000 performance measurements and was validated by determining Pearson's correlation, Spearman's rank correlation and maximum deviation from linearity. Furthermore, through the Hardware Signature of the analytical models, one can obtain precise answers to questions about optimum size of memory, caches, and the numerical precision for a given clock rate.


Abstract Transcatheter pulmonary valve replacement is fast becoming an accepted alternative to repeat surgical pulmonary valve replacement for selected patients and therefore a complementary strategy in the long-term management of those requiring surgical pulmonary valve replacement. With a combined surgical and percutaneous approach, late morbidity for some of these patients may be diminished. This manuscript will review the current indications for this procedure, its limitations, and its benefits.


Magnetorheological (MR) gels consist of micron sized magnetic particles inside a gel matrix. Before physical cross-linking, the suspension is subjected to a small magnetic field which creates a particle string structure. After cross-linking, the string is kept within the gel at room temperature. Under an external homogeneous magnetic field and mechanical deformation, the soft swollen gel matrix allows the string to largely rearrange at microscopic scales. With the help of two homemade magneto cells mounted on an optical microscope, we were able to follow the conformational change and instabilities of a single magnetic particle string under the combined influence of shear (or stretch) and the magnetic field. In the absence of mechanical deformation, an external magnetic field, applied in the perpendicular direction to the string, breaks it into small pieces generating periodic structures like sawteeth. When an external magnetic field is applied parallel to the pre-aligned string, it exhibits a length contraction. However, under shear strain perpendicular to the original pre-structured string (and magnetic field), the string breaks and short string segments tilt, making an angle with the original direction that is smaller than that of the applied shear (non-affine). The difference in tilt angle scales with the inverse length of the small segments L-1 and the magnetic flux density B, reflecting the ability of the gel matrix to expel solvents under local stress.


This paper presents an in-depth survey on network bandwidth allocation policies and discuss design methodologies of distributed rate calculation algorithms in packet-switched networks. In particular, we discuss two rate allocation policies: the generalized max-min and the generic weight- proportional max-min policies, both of which generalize the classical max-min rate allocation policy. For the design of distributed algorithms to achieve these two rate allocation policies, we focus on rate-based distributed flow control where special control packets are employed to achieve the information exchange between a source and the network. We categorize two broad classes of distributed rate calculation algorithms in the literature using live algorithms as illustrations. We compare the design tradeoffs between these two classes of algorithms in terms of performance objectives and implementation complexities and discuss important extensions within each class of algorithms.


Lane keeping assistant system (LKAS) could save thousands of lives each year by maintaining lane position and is regarded as a promising active safety system. The LKAS is expected to reduce the driver workload and to assist the driver during driving. This paper proposes a model based predictive controller for the LKAS which requires cooperative driving between the driver and the assistance system. A Hardware-In-the-Loop-Simulator (HILS) is constructed for its evaluation and includes Carsim, Matlab Simulink and a lane detection algorithm. The single camera is mounted with the HILS to acquire the monitor images and to detect the lane markers. The simulation is conducted to validate the LKAS control performance in various road scenario.


ABSTRACT This article provides an empirical overview of political polarization in Korea from 2004 to 2021 based on a wealth of longitudinal surveys. We consider elite as well as mass polarization, document the extent of ideological polarization in terms of standard left-right measures, and consider more specific forms of polarization, including affective polarization and the specific issues that are proving divisive. We find that polarization in the country has increased over time, but not among the electorate as a whole. Rather partisan identifiers and party activists of the two main parties have shown a movement towards the extremes in terms of ideology, issue positions, and aversion towards the other party. For both legislators and the voting public, the substantive scope of political polarization is widening, encompassing not only foreign policy but also economic issues that had not seen strong signs of partisan divergence in the past.


This essay redefines the crisis of historicism as a collapse of trust. Following Friedrich Jaeger, it suggests that this crisis should be understood, not as a crisis caused by historicist methods, but as a crisis faced by the classical historicist tradition of Ranke. The "nihilism" and "moral relativism" feared by Troeltsch's generation did not primarily refer to the view that moral universals did not exist; rather, they expressed that the historical justification of bildungsburgerliche values offered by classical historicism did no longer work. In Niklas Luhmann's vocabulary, this is to say that moral values could no longer be trusted on historical grounds. But when the "reduction of complexity" offered by classical historicism collapsed, Troeltsch's generation faced a justification problem: what other modes of justification, if any at all, were available in a time of increasing secularization and growing feelings of discontinuity with the past? In identifying the crisis of historicism with this moral justification problem, this essay helps explain why such debts of despair could be reached in the early-twentieth-century disputes over historicism.


Washington, D.C. - Of the approximately 19 cases of linear atrophoderma of Moulin described in the literature; all of them presented in children or young adults less than 20 years of age -- until, perhaps, now. Gina C. Ang, M.D., and colleagues at Philadelphia's Jefferson Medical College, may have identified the first case of congenital linear atrophoderma, or at least the first one to come to the attention of the medical community.


This paper presents a study on power grid disturbance classification by Deep Learning (DL). A real synchrophasor set composing of three different types of disturbance events from the Frequency Monitoring Network (FNET) is used. An image embedding technique called Gramian Angular Field is applied to transform each time series of event data to a two-dimensional image for learning. Two main DL algorithms, i.e. CNN (Convolutional Neural Network) and RNN (Recurrent Neural Network) are tested and compared with two widely used data mining tools, the Support Vector Machine and Decision Tree. The test results demonstrate the superiority of the both DL algorithms over other methods in the application of power system transient disturbance classification.


As technology improves, more and more aspects of games move closer to the human life and activities, including the way people interact and socialize with each other within their community. Pokemon Go is one of those games that utilize the social aspect of its players. This paper aims to maintain that in the process of playing Pokemon Go, the player greatly involve in a social engaging experience, and it is all possible with the help from the visual aid from the visual communication design. (Abstract) Keywords—Pokemon Go, Social Value, Social Capital, Visual Communication Design for Game Design


In this work, a novel solution to the speaker identification problem is proposed through minimization of statistical divergences between the probability distribution (g). of feature vectors from the test utterance and the probability distributions of the feature vector corresponding to the speaker classes. This approach is made more robust to the presence of outliers, through the use of suitably modified versions of the standard divergence measures. The relevant solutions to the minimum distance methods are referred to as the minimum rescaled modified distance estimators (MRMDEs). Three measures were considered - the likelihood disparity, the Hellinger distance and Pearson's chi-square distance. The proposed approach is motivated by the observation that, in the case of the likelihood disparity, when the empirical distribution function is used to estimate g, it becomes equivalent to maximum likelihood classification with Gaussian Mixture Models (GMMs) for speaker classes, a highly effective approach used, for example, by Reynolds [22] based on Mel Frequency Cepstral Coefficients (MFCCs) as features. Significant improvement in classification accuracy is observed under this approach on the benchmark speech corpus NTIMIT and a new bilingual speech corpus NISIS, with MFCC features, both in isolation and in combination with delta MFCC features. Moreover, the ubiquitous principal component transformation, by itself and in conjunction with the principle of classifier combination, is found to further enhance the performance.


Imaging-based determination of tumor grade is highly desirable, particularly for pediatric brain tumors where surgical biopsy carries considerable risks. We have applied a novel diffusion model – varying diffusion curvature (VDC) model, with two b-value ranges (0-2000 sec/mm2 and 0-4000 sec/mm2), to differentiate between low- and high-grade pediatric brain tumors on 70 patients. Our results showed that the combination of the VDC parameters substantially outperformed the ADC for differentiating low- from -high grade pediatric brain tumors. Increasing the maximal b-value from 2000 to 4000 sec/mm2 did not noticeably improve the performance.


Astrotheology is that branch of theology that provides a critical analysis of the contemporary space sciences combined with an explication of classic doctrines such as creation and Christology for the purpose of constructing a comprehensive and meaningful understanding of our human situation within an astonishingly immense cosmos. Within the growing field of Religion and Science, astrotheology and its sister subject, astroethics, represent critical responses to the excitement permeating the space sciences, especially astrobiology. The excitement arises because of new searches for microbial life within the solar system and the discovery of exoplanets elsewhere in the Milky Way, some of which may be homes for extraterrestrial intelligent civilizations.


The large-scale fluorescence microscopy has enabled the observation of dynamic physiological activities at the single cellular level across the mouse cortex, such as distributed neuronal population representations. However, video-rate high-resolution microscopy at sophisticated biological surfaces in nature keeps a challenging task for the tradeoff between the speed, resolution, and field of view. Here we propose Spinning Disk Multifocal Microscopy (SDiM) for arbitrarily shaped surfaces, which enables imaging at centimeter field-of-view, micrometer resolution and up to 30 frames per second across the depth range of 450 µm. We apply this technique in various microscopic systems, including customized macroscopic systems and the Real-time Ultra-large-Scale imaging at High resolution macroscopy (RUSH), in both the reflective mode and the fluorescence mode, and in the study of cortex-wide single-neuron imaging and immune cell tracking. SDiM provides an opportunity for studying the cortex-wide multi-scale cellular interactions in biological tissues.


contribute strengthening and provocative thought on God and man, both in prose and in verse. And the voices are those of Roman Catholics, Anglicans, Protestants of various denominations, Jews, and two eminent unbelievers. The selections are grouped under six broad headings: The Idea of God, The Idea of Man, The Secular Challenge, Religion and Science, Creation and Existence, and Faith. The editor has taught at Columbia University, Kent School, and S1. Stephen's School, Rome. He is the author of three novels and several non-fiction works. His religious concern and his wide range of interests eminently qualify him to make this selection of readings. James W. Cox


Objective The disruption of dual antiplatelet therapy (DAPT) causes more adverse events after percutaneous coronary intervention (PCI). However, incidence and predictors of DAPT non-compliance are unknown in chronic coronary syndrome patients when compared between planned and ad hoc PCI. Methods This investigation was aimed to assess the incidence, predictors, outcomes, and primary mode of non-compliance of DAPT in patients with chronic coronary syndrome undergoing their first PCI. We analyzed the patients between planned (group 1) and ad hoc (group 2) PCI. Results There were a total of 628 participants in this investigation (370 were in planned PCI and 270 in the ad hoc PCI group). Out of 628 patients, by one month, 10% left DAPT in planned PCI group and 19.7% in ad hoc PCI group (aOR: 0.451, 95% CI: 0.285–0.713, p = 0.001). At 12 months, DAPT non-compliance was significantly more in ad hoc PCI group (52.7% vs. 47.8%; aOR: 0.647 95% CI: 0.470–0.891, p = 0.008). Age > 65 years (p < 0.001), low education status (p = 0.012), residents of rural areas (p < 0.001), ad hoc PCI group (p = 0.036), and angina class II (p = 0.038) were predictors for DAPT non-compliance in this cohort. Conclusion Approximately 5 out of 10 patients disrupt DAPT due to non-compliance. This investigation provides an insight on additional predictors of non-compliance to DAPT, helping us to identify and address specific patient-related factors for disruption.


OBJECTIVE
We investigated whether an association existed between single motherhood and neonatal mortality among twins and whether such a linkage varied by race.

STUDY DESIGN
Retrospective cohort analysis on 446,570 twin live births (between 24-44 gestational weeks inclusive) in the United States from 1995 through 1998. Neonatal survival was compared between twins of single and those of married mothers for blacks and whites separately using Cox proportional hazards regression that adjusted for the confounding effects of education, parity, adequacy of prenatal care and maternal smoking during pregnancy. The Robust Sandwich Estimator was employed to adjust for intracluster correlation.

RESULTS
The rates for neonatal mortality among blacks were 34.9 per 1,000 among married and 43.4 per 1,000 among single mothers. Among whites, the rates were 20.6 per 1,000 for married and 28.9 per 1,000 for unmarried mothers. Neonatal mortality was significantly elevated among white twins of single mothers (Hazard Ratio (HR) = 1.23; 95% Confidence Interval (CI) = 1.14-1.31) and among black twins of single mothers (HR = 1.12; 95% CI = 1.01-1.25). However, when gestational age was adjusted for, the association between single motherhood and neonatal mortality disappeared.

CONCLUSION
Single motherhood was a risk factor for neonatal mortality among twins, and the disparity in survival was more accentuated among whites. The association between single motherhood and neonatal mortality was explained by the preponderance of preterm births among twins of unmarried gravidas. Our findings reinforce the importance of future research to develop and test interventions that will decrease the incidence of preterm birth.


Recent studies [13, 18] have shown that clearing schemes are efficient multi-modal optimization methods. They efficiently reduce genetic drift which is the direct reason for premature convergence in genetic algorithms. However, clearing schemes assumed a landscape containing equal-spaced basins when using a fixed niche radius. Further, most clearing methods employ policies that favor elitists, thus affecting the explorative capabilities of the search. In this paper, we present a valley adaptive clearing scheme, aiming at adapting to non-uniform width of the valleys in the problem landscape. The framework of the algorithm involves hill-valley initialization, valley-adaptive clearing and archiving. Experimental results on benchmark functions are presented to demonstrate that the proposed scheme uncovers more local optima solutions and displays excellent robustness to varying niche radius than other clearing compeers.


We clarified that Fermi levels at InGaAs MOS interfaces are pinned inside conduction band (CB) and that this pinning severely degrades the effective mobility. Also, the energy position of the Fermi level pinning (FLP) is found to be tunable. It is experimentally shown that the increase in the difference between the FLP position and the CB minimum (CBM) leads to high mobility at high Ns region. Also, possible physical origin for this FLP is proposed.


Part of the larger debate on why technology enhanced learning (TEL) has possibly not lived up to early expectations (Rossiter, 2007; Laurillaurd, 2010; Selwyn, 2010) is the barriers preventing lecturer participation. Some the barriers identified include a lack of time/too much work, (Jenkins, Browne, Walker and Hewitt, 2011; Lesht and Windes, 2011), fear of technology and concerns over loss of control and loss of academic identity (Gonzales, 2012; Hanson, 2009). Busy lecturers are faced with the dual problem of needing to incorporate at least some elements of TEL into their delivery strategy while finding time to unravel the seemingly bewildering range of TEL options and platforms. Drawing its inspiration from TED talk's time-controlled presentation format, the eChunks series sought to address some of these concerns by filming brief face-to-face information sessions and then making those sessions available online via the institute's VLE. Aimed at lecturers who are beyond late adapters, eChunks are distinguishable because they are pre-training sessions, a 'taster' so attendees who have yet to adopt TEL are able to make an informed decision about which technologies they may be interested in and what further training they need and want. For the higher education sector, the eChunks initiative offers a possible avenue into the TEL environment for those lecturers who, for a variety of reasons, have yet to make the leap. The sessions are deliberately short and responsive to current constraints in that they avail of existing training material and focus on open source applications. This presentation will incorporate a reflective piece by the authors on the eChunks design and delivery process and a survey of eChunk attendees that sought to identify the profile of those using technology and the impact of eChunk on their teaching and learning.


outer quadrant as a rounded mass about four disc diameters across. It was raised four diopters. Surrounding the area were a few scattered patches of rarefied atrophic retina. Between these and the extreme periphery the retina appeared to be unaffected. The vitreous was quite clear, and no other abnormality of any sort was detectable. The intra-ocular tension was normal. There had never been any pain. In the charts of the visual fields was a large scotoma corresponding in size to the mass, and sharply delineated. The intact retina between the mass and the periphery could be plotted, so that at the nasal limit of the field the scotoma was bordered by a tongue-like elongation of the field vision. The Wassermann reaction was negative. During the last three months the swelling has become very slightly larger and the atrophic areas at the lower limit are now detached. A very slight cedema of the macula has developed. The vision now is a partial W and the patient is still comfortable. While concluding that this mass (which lies too far back for ordinary transillumination) must be a solid detachment, and presumably a choroidal melanotic sarcoma, the possibility of its being a form of cyst into which hwemorrhage has occurred has been considered. In support of this latter diagnosis, the rarefied patches were regarded as being the outskirts of a large area of old choroidoretinitis. The clear media and the absence of similar patches elsewhere in either eye tend to detract from the cyst diagnosis. In any case removal of the eye is the safest course.


Accurate scientific predictions of the true human health outcomes of global climate change are significantly confounded by several effect modifiers that cannot be adjusted for analytically. Nevertheless, with the documented increase in average global surface temperature of 0.6 C. since 1975, there is uniform consensus in the international scientific community that the earth is warming from a variety of climatic effects, including cyclical re-warming and the cascading effects of greenhouse gas emissions to support human activities.


In the future, learning will take the shape of a story, a play, a game; involving multiple platforms and players; driven by dialogue and augmented with technology, an interplay of immersive experiences, data, and highly social virtual worlds (Lee et al., 2021).
Employers seek graduates who demonstrate attributes that organisations require to develop in the future. As students transition out of higher education, they should have the 'abilities and capabilities to maintain employment' (Asiri et al., 2017 p. 2). The transition out of university can be perceived as particularly stressful, with uncertainty about what is required for a successful career (Jackson and Tomlinson, 2020). This is exacerbated in the post Covid-19 environment when, even as the graduate job market has started to recover, students' confidence about finding a job after graduation remains low (Curnock Cook, 2022). Our simulation methods are aligned to the theories that underpin these transitions,  and designed to support students  'becoming' professionals in their field. Simulations can be designed for cognitive absorption, the psychological concept of flow and deep absorption in learning (Kukulska-Hulme et al., 2022). Premised on the innovation of best learning moments, the student tasks shared in this workshop engender deep involvement, through memorable learning activities. This reflects the 'ways of working' of the Learning Development (LD) community, and evidence suggests that reflective practice, learning complex skills and scaffolding learning are the transferable aspects of these technologies (Chernikova et al., 2020).
Widening participation research has provided evidence that students' movements in and out of experiences such as care, work and studies are dynamic, non-sequential and context-dependent (Holley and Priego-Hernández, 2021). With the move to hybrid learning, students want their learning materials to be well-designed. However, 43% of students do not perceive their learning materials to be engaging/motivating (Killen and Didymus, 2022). Immersive technology and simulation may offer the solution to this disconnect, as simulations offer an immersive and embodied experience (Bayne 2004; Bayne et al., 2019). Signature pedagogies (Thomson et al., 2012) for professions can provide a means for institutions to achieve the requirements of Office for Students' B3 (2022) which is now assessing student continuation, degree outcomes, including differential outcomes for student characteristics, and, framing this workshop, graduate employment and progression to professional jobs and postgraduate study.
Learning Developers have a pivotal part to play operationalising actions that result into students' graduate outcomes, and responding to this, our workshop invited participants to experience three types of simulation: a) a business game; b) a mass casualty evacuation; and c) a community project responding to a scenario.


Efficient reservoir sweep is critical for operators to boost oil production in the Middle East. This task becomes particularly challenging in carbonate formations, which typically feature permeability ranging from microscopic pores to large cavernous vugs. Extreme heterogeneity disserves water injectors, leading to nonuniform injection profiles. Consequently, water sweeping is inefficient and leaves significant residual oil behind. In the Mesopotamian Basin, the matrix stimulation approach was rethought to address high permeability contrasts and produce the bypassed oil.
 The methodology relied on coiled tubing (CT) equipped with fiber optics and real-time downhole measurements, a CT-deployed inflatable packer, and a high-pressure rotary jetting tool. The array of downhole readings was leveraged to ensure optimal use of the bottomhole assembly. The high-pressure rotary jetting tool was used in the first run to condition the wellbore tubulars across the inflatable packer planned anchoring depth. In the second run, the inflatable packer was set at the target depth, and the stimulation treatment was selectively pumped either above or below the packer, depending on the depth of the interval of interest.
 The proposed stimulation technique was implemented in more than 40 wells, which included vertical and deviated water injectors, completed with 3 1/2-in. or 4 1/2-in. tubing and up to 7-in. casing, with two to five perforated intervals averaging 30 to 50 m in total, temperatures ranging from 90 to 140°F, and an average meadured depth of 2500 m. The CT-deployed inflatable packer had an expansion ratio of up to 3 to 1. CT real-time downhole measurements, such as CT internal pressure, CT annulus pressure, temperature, downhole axial forces, gamma ray, and casing collar locator (CCL), were instrumental to eliminate the uncertainties associated with changing downhole conditions and depth correlation. They also enabled a controlled actuation of the downhole tools in subhydrostatic wells, as the pressure imbalance caused by the low bottomhole pressure can generate loss of fluid flow and pressure across the tools. For the first time, the operator was able to stimulate the tight rock in water injector wells, enhancing injection sweeping efficiency and boosting oil production from offset wells. As a result of this campaign, production gains are estimated at 60,000 BOPD, and injectivity increased in average 2 times per intervention. This approach has now become the state of the practice for the operator to stimulate wells with high permeability contrast.
 This enhanced matrix stimulation technique, leveraged by CT and real-time downhole measurements, brings a new level of confidence to accurately and effectively deploy inflatable packers in wells with challenging expansion ratio and low reservoir pressure. In addition, the proposed technique enables stimulating tight rock across intervals with extreme heterogeneity, resulting in a more efficient sweep and an increase in oil production.


OBJECTIVE
Despite high prevalence rates of pain among older adults, relatively few studies have examined the impact of the Arthritis Foundation Self-Help Program (ASHP) in this age group, particularly older minority groups.

DESIGN
This study compared the effects of the ASHP on groups of Hispanic, African American and non-Hispanic White older adults.

SETTING
Three senior centers in New York City.

PARTICIPANTS
Data are presented for 112 (37 African American, 38 Hispanic and 37 non-Hispanic White) participants (mean age= 75 years) age 60 and over with diverse noncancer pain disorders.

INTERVENTION
Participants enrolled in the 6-week Arthritis Self Help Course.

MAIN OUTCOME MEASURES
Participants were surveyed before and after course completion (in person) and at 18 weeks (by telephone). Demographic and clinical data were collected at baseline; outcomes included pain, mood, self-efficacy, and number of days per week spent exercising.

RESULTS
All three groups experienced significant decreases in pain intensity (P< or =.05). Significant improvements were also found in mood scores for non-Hispanic White (P=.01) and Hispanic participants (P=.03). Hispanic participants also evidenced significant improvement in their confidence to self-manage pain (P=.003) and reported fewer arthritis-related symptoms (P=.02). All three race/ethnicity groups reported substantial increases in the number of days spent doing stretching, endurance and relaxation exercises (P< or =.01).

CONCLUSION
Positive results were noted for all three race/ethnicity groups, particularly in the areas of pain reduction and uptake of stretching, endurance and relaxation exercises. Our findings support efforts to disseminate broadly the ASHP in community settings that serve older African American, Hispanic and non-Hispanic white adults.


Bacillus stearothermophilus phosphoglycerate mutase (PGM), which interconverts 2‐ and 3‐phosphoglyceric acid (PGA), does not require 2,3‐diphosphoglyceric acid for activity. However, this enzyme does have an absolute and specific requirement for Mn2+ ions for catalysis. Here we report the crystal structure of this enzyme complexed with 3PGA and manganese ions to 1.9 Å resolution; this is the first crystal structure of a diphosphoglycerate‐independent PGM to be determined. This information, plus the location of the two bound Mn2+ ions and the 3PGA have allowed formulation of a possible catalytic mechanism for this PGM. In this mechanism Mn2+ ions facilitate the transfer of the substrate's phosphate group to Ser62 to form a phosphoserine intermediate. In the subsequent phosphotransferase part of the reaction, the phosphate group is transferred from Ser62 to the O2 or O3 positions of the reoriented glycerate to yield the PGA product. Site‐directed mutagenesis studies were used to confirm our mechanism and the involvement of specific enzyme residues in Mn2+ binding and catalysis.


Web openings can be used to pass utilities through beams and to minimize story height. Decreasing building height reduces both the exterior surface and the interior volume of a building, which lowers operational and maintenance cost, as well as construction cost. Recently, using composite structures and PEBS(Pre-Engineered Building System) has steadily increased. Sometimes it requires non-compact section for web to reduce steel usage. According AISC Design Guide, the web opening should be only provided in the compact section. In this study, the changes in buckling load, yielding strength, and the deformation of specimens were evaluated experimentally for the non-compact section steel beam.


Transgender community faces insulting remarks and people treat them in a bad way. Discrimination is being faced by transgender at all levels such as at school, in family, at places where they live. The purpose of the present study was to explore the attitude of people towards third gender. A sample of 600 were selected through purposive sampling and snow ball sampling techniques. Data was collected from Two cities of Pakistan Sahiwal and Multan. Demographic variables of participants used in this research are age, gender, monthly income, qualification and marital status. Attitude towards Hijras scale was used in this research. Results showed that females have more acceptances of Hijra's (transgender) rights and status as compared to males. Males and females don't want any close relationship with Hijras (transgender).Sexual issues (SI) are significant in males as compared to females. Education has more impact on people's attitude towards Hijra community. People belonging to religious groups have more negative attitude towards Hijras as compared to other groups.


The solution of elasticity problems involving the interaction between dislocations and cracks plays a fundamental role in many practical and theoreticM applications. Although elasticity problems involving dislocation or cracks in quasi-crystals have been investigated in many papers, the analysis is limited to a single defect. This paper investigates the interaction of defects in one-dimensional hexagonal quasi-crystMs using the complex variable function method. The interaction force between two parMlel dislocations is presented and the analytic solutions of elastic fields of interaction between a dislocation and a crack are obtained. A version of the well-known Peach-Koehler formula in one-dimensional hexagonal quasi-crystals is given.


To lessen overwhelmed high human strain and tedious work in urea application for rice cultivation, a manually operated push type Urea Super Granule (USG) applicator was designed and developed. There are four small drive wheels inserted in lieu of float which was fabricated using small steel rings instead of the traditional skid concept. The discharge tubes were reformed with the additional bent PVC tubes. The average effective field capacity and field efficiency of the USG applicator was 0.16 ha h and 88.1%, respectively. In the field test, the average missing rate, applicator capacity, the distance amid two dropped USG, covering performance and force requirement in developed model were 6.25%, 13.21 kg h, 41.61 cm, 77.5% and 69.18 N. The developed applicator saves cost about nineteen times than manual operation. The developed applicator may be useful to small growers of rice growing countries like Bangladesh which not only be cost effective but will also save both time and energy.


Terahertz (THz) metamaterials have recently attracted much interest due to their ability to tune propagation properties using sub-wavelength structures. In this paper we demonstrate the first metamaterial device developed by patterning a vanadium dioxide (VO2) wire-grid structure onto a c-sapphire substrate. Temperature and polarization dependent THz time-domain spectroscopy transmission measurements are taken to evaluate the device performance as a function of the metamaterial parameters. The transmission variance with polarization is enhanced by increasing the filling factor of the wire-grid structure.


This article highlights some of the issues and challenges facing the siblings of autistic children. Sibling relationships are critical to interpersonal development. The birth of an autistic child brings issues of mourning and loss to the fore, forcing family members to readjust their fantasies, wishes, and expectations associated with "primary (maternal) preoccupation" (Winnicott, 1956) prior to the birth of the autistic child. Siblings (and families) may respond with denial, masochistic submission, guilt, and reaction formation, among other reactions. Implications for intervention, notably in the areas of psycho-education and clear communication, are discussed.


Gravity adds about 40-50 mmHg perfusion pressure to the arterial supply of the quadriceps muscles in the upright posture. This could have important implications in supply of blood flow during exercise. Recently, we have shown that when subjects exercise in the supine posture the rate of increase in VO2 is considerably slower then when cycling exercise takes place in the upright posture. The most probable explanation for this slower adaptation was the altered perfusion gradient. Indeed, when the perfusion gradient from heart to legs was restored by placing the lower part of the body of supine subjects in a negative pressure chamber, the rate of increase in VO2 returned to upright values. The hypothesis advanced from these studies was that skeletal muscle blood flow was reduced at the onset of supine exercise. Exercise in the microgravity environment of space should be similar to that in the supine posture. The only experiments conducted in space to this date that have addressed the question of cardiorespiratory adaptation to changing work rates were performed on the German D2 mission using the methodology proposed by Stegemann and colleagues. To conduct these experiments, it is necessary to utilize sensitive breath-by-breath technology. Recently, NASA and the Russian space programs have commissioned a new mass spectrometer based system as part of the GASMAP project. It was the purpose of this study to evaluate the new mass spectrometer under conditions in which the gravitational effects on the cardiorespiratory response were being challenged.


ABSTRACT The purpose of this study was to examine perspectives on childhood, coping methods and reasons for deciding to major in education among undergraduates with Attention Deficit Hyperactivity Disorder (ADHD). While the experiences of children and adolescents with ADHD have been the focus of much research, empirical evidence is lacking regarding the experiences of education students with this disorder. This research seeks to correct this lacuna and in particular to shed light on what motivates students to return to a setting they experienced as so difficult and complex. We used qualitative-phenomenological research methods to examine 30 education students diagnosed with ADHD. Complex childhood experiences emerged during the course of the research. The study participants noted difficulties in remaining attentive, a high level of distractibility, a heightened need to move around and a lack of focus. These symptoms caused them difficulties at school, harmed their self-image and left them with feelings of frustration, failure and jealousy towards their classmates. The participants raised mainly altruistic considerations in explaining why they chose the teaching profession, alongside a negative view of the education system.


Around the world, increasing population is heightening the food and feed demand. Fruit production is playing vital role in augmented food availability, improved nutrition, livelihood, employment opportunities and economy of Nepal. Given the low mechanization in horticultural crops especially for fruits cultivation in nation, the production is by far based on physical labour source (human power). However, the rising cost and decreasing availability of farm labour has heightened interest in mechanization. There is no doubt that farm mechanization has substantial role in boosting the scale of farm operations, lessening the production cost, tumbling drudgery, enlightening the timeliness of operations, augmenting crop productivity and contributing to improve food security and rural livelihoods. This paper has attempted to give a short glimpse of fruit mechanization status and development of Nepal. It has focused more on fruit production and mechanization status, issues and research gaps, available machinery and tools of different farm operations, challenges and constraints along with way forward for fruit development. Although the country has some positive moves in fruit mechanization area (especially in tillage), the level of fruit mechanization is very poor with respect to mechanical power (especially in hills), effective tools and implements, irrigation, pest, and orchard management, harvesting and post-harvest technology areas. The physical constraints of rugged terrain and steep topography, small and fragmented turfs, lack of skilled manpower, poor facilities of spare parts, repair and maintenance, low investing capacity of the farmers, lack of awareness among farmers and non-availability of farm implements and machine based on gender and agroecology are some of the main bottleneck for low level of mechanization in the country. Despite various constraints, there is an enormous opportunity to integrate appropriate machines into most cultivation tasks in a way that optimizes productivity of land and farmer's life and economy. Making the best use of these machines requires a holistic approach that considers the ecological belt, topographical characteristics, fruit cultivar and equipment available. Therefore, a widespread participatory research method is required to test, validate and disseminate the fruit machinery and tools performance compared with traditional farming method. In fact, operation wise mechanization of orchard crops including nursery house, transplanting of saplings, pit making, spraying and weeding in tall crops and harvesting of fruits and post-harvest operations are prime intervention areas of current situation. Furthermore, immediate attention of the government and other bodies is required to strengthen and rejuvenate unproductive old orchards farm with proper tools and mechanism. Overall, this study highlights the need to prioritize and strengthen fruit mechanization research based on agro ecology and farmers need, improve credit access and spare parts, invest in technical human resources and agricultural machinery workshop, targeted subsidy for poor, women and youth friendly enterprises or real farmers following proper monitoring, incentivize local fabrication and, effective extension and custom hiring services to address the mechanization gaps and harness the potentiality of fruit development.


The effectiveness of monetary and fiscal policies is an issue which is continuously discussed but could not be reached to any solution. In fact, the essence of the issue is based on the Monetarist-Keynesian debate. Monetarists favour monetary policy while Keynesian favour fiscal policy in the sense of effectiveness. In this study, it has been examined whether monetary or fiscal policy is more effective in Turkish economy. The variables GDP, money supply (M2) and public expenditures are employed in the study. The data used are quarterly and cover the period 1987:Q1-2007:Q3. According to the findings obtained from the results of ARDL approach, fiscal policy is more effective than monetary policy in Turkish economy and its effect is negative.


We present a novel approach to image manipulation and understanding by simultaneously learning to segment object masks, paste objects to another background image, and remove them from original images. For this purpose, we develop a novel generative model for compositional image generation, SEIGAN (Segment-Enhance-Inpaint Generative Adversarial Network), which learns these three operations together in an adversarial architecture with additional cycle consistency losses. To train, SEIGAN needs only bounding box supervision and does not require pairing or ground truth masks. SEIGAN produces better generated images (evaluated by human assessors) than other approaches and produces high-quality segmentation masks, improving over other adversarially trained approaches and getting closer to the results of fully supervised training.


Sulfide samples from the Logatchev hydrothermal field (14 degrees 459 N, Mid-Atlantic Ridge), which occurs on an ultramafic substrate, show a bimodal distribution of copper- and zinc-rich mineralogies, both of which have elevated gold contents. The copper-rich vents show an unusual depression,hosted morphology with few chimney structures. Copper-rich samples show evidence for a primary gold-copper association, as well as gold concentration during small-scale replacement and reworking processes. Evidence from vent morphologies, Au/Ag ratios, and sulfidation state suggest that, in the copper-rich samples, gold was not transported as Au(HS) (super -) 2 .


The paper summarizes five-year experience with mechanically detachable microspirals for embolization of 62 arterial aneurysms in 59 patients. The complications and technical problems associated with both the specific features of this technology and anatomic types of the structure of vessels and aneurysms are described. Methods for the prevention and treatment of these complications are proposed.


Cloud computing has a character of low manintance which will provide an effective solution to share resource among group of users in the cloud. Major problem in public cloud is how to share data's and documents based on fine grained access control policies, due to frequent change of the membership data sharing in dynamic groups to preserve data and identity privacy from a cloud which is a untrusted one is still a challenging issue. Encrypting the Document with different key such as Attribute Based Encryption and Proxy Re-Encryption have many draw backs .These approaches is efficient to handle user registration and revocation. It requires maintaining many encrypted copies of the single document, which incurs high computational costs. In this paper we propose a privacy preserved multi owner data sharing scheme, named Suody.By taking maximum advantage of group signature to construct homomorphic authenticators, signed receipts and dynamic broadcast encryption techniques, a user in the cloud can share the data with others using withheld authorship. At the same time overhead in the storage and computation cost for encryption of our scheme for the number of users revoked are independent .Additionally, we also analyze schemes security with rigorous proofs. Index Keywords: Cloud computing, data sharing, dynamic groups.


Systematic evaluation of cortical differences between humans and macaques calls for inter-species registration of the cortex that matches homologous regions across species. For establishing homology across brains, structural landmarks and biological features have been used without paying sufficient attention to functional homology. The present study aimed to determine functional homology between the human and macaque cortices, defined in terms of functional network properties, by proposing an iterative functional network-based registration scheme using surface-based spherical demons. The functional connectivity matrix of resting-state functional magnetic resonance imaging (rs-fMRI) among cortical parcellations was iteratively calculated for humans and macaques. From the functional connectivity matrix, the functional network properties such as principal network components were derived to estimate a deformation field between the human and macaque cortices. The iterative registration procedure updates the parcellation map of macaques, corresponding to the human connectome project's multimodal parcellation atlas, which was used to derive the macaque's functional connectivity matrix. To test the plausibility of the functional network-based registration, we compared cortical registration using structural versus functional features in terms of cortical regional areal change. We also evaluated the interhemispheric asymmetry of regional area and its inter-subject variability in humans and macaques as an indirect validation of the proposed method. Higher inter-subject variability and interhemispheric asymmetry were found in functional homology than in structural homology, and the assessed asymmetry and variations were higher in humans than in macaques. The results emphasize the significance of functional network-based cortical registration across individuals within a species and across species.


The Dose Verification System (DVS®) is the first implantable radiation dosimeter designed for in situ measurement of dose delivered to the tissue being irradiated. The success of radiation therapy is predicated on maximizing tumor cell death and minimizing normal tissue toxicity. Tumor control increases with the delivery of appropriate radiation doses to the target area. These doses have been determined from in vitro and animal studies, which generated specific dose–response data. However, there has not been a practical system available to ensure that the appropriate dose was being delivered in situ to monitor the daily patient dose during radiation therapy. Studies have shown that dose variations can occur. Recently completed pivotal clinical studies using the DVS found a greater than 7% (positive or negative) change in cumulative dose in seven out of 36 (19%) breast cancer patients; and six out of 29 (21%) and eight out of 19 (42%) patients during large-field and boost irradiation of the prostate. The device is an important step to enable physicians to expand the concept of individualization of therapy.


Gastrointestinal complaints are the most frequent side effects of antineoplastic chemotherapy behind the bonemarrow depressions. Nearly all cytostatic drugs, favourably used treating gynaecological malignant tumours, show a high complication rats on the part of the digestive organs. Primary an secondary damages can be so serious that the continuation of an effective tumour therapy becomes impossible. Whereas mucous excitement and motility disturbances are caused by local toxicity of cytostatic drugs, on the other hand central and psychogenic factors are of essential importance concerning nausea and vomiting. Therefore all these side effects could not be treated effective antiemetics alone. Only by an ingenious combination of medical treatment, psychological guidance and appropriate nutrition complaints can be relieved so far that the patients quality of life is interfered as less as possible and that a sufficient compliance may be reached.


Indigenous chickens (IC) play an important role in African rural household settings, particularly in improving their livelihoods. However, IC production is characterised by low productivity due to poor quality and quantity of feed, compounded by poor management practises. This dire situation is aggravated by the fact that IC are raised under extensive systems, supplemented with meagre grain supplements. They are a hardy poultry species and as a result most farmers assume that their nutritional requirements can be met through scavenging. To the contrary, analysis of crop contents has shown that IC nutritional intake levels are often below optimum for production. To enhance the productivity of IC, there is urgent need to explore the use of alternative nutritionally rich feed stuffs. One of such ingredients is Quality Protein Maize (QPM). Quality protein maize contains elevated levels of lysine and tryptophan, compared to non-QPM. The objective of this article is to review the prospects of QPM as feed for IC, through a strengths, weaknesses, opportunities and threats analysis. Due to its superior nutritional quality, QPM has the potential to enhance growth rate, carcass characteristics and immunity of indigenous chickens. However, QPM is still a new technology in Zimbabwe; most farmers are not aware of its existence. There is, therefore, need for policies and infrastructural adjustments to promote its widespread adoption. Furthermore, there is need for feeding trials as they provide concrete evidence of the benefits of this kind of maize. Key words: Carcass quality, quality protein maize, supplementary feed


Transcription factors (TFs) are important oncogenic regulator and are altered during tumor initiation and progression. Our oncogenomic analysis of gene expression data from large clinically-annotated patient samples identified TF Dp1 as one of the most important gene affecting both overall and event-free survival in multiple myeloma (MM). Elevated Dp1 expression was predictive of adverse clinical outcome, independent of Dp1 protein partners, E2Fs and RB, suggesting direct impact of Dp1 and providing the rationale to further evaluate its specific role in MM.

We have observed high level of Dp1 expression and activity in MM cells which was further induced after interaction with bone marrow stromal cells (BMSC). Moreover, Dp1 knock-down using specific sh-RNA decreased MM cell growth in 5 MM cell lines with different genetic background, with a concomitant G1 arrest and late induction of apoptosis. These data suggest a role for Dp1 in MM cell proliferation and survival and established a rationale to identify its molecular impact.

We have further characterized Dp1 activity using chromatin immunoprecipitation with Dp1 or E2F1 specific antibody followed by genome wide sequencing (ChIP-Seq) to identify Dp1-binding regions in MM. We have identified 2783 exclusive Dp1 binding regions in two MM cell lines. Examination of Dp1 and E2F1 binding revealed that Dp1 co-occupies 65% of the binding sites with E2F1. The DAVID gene set enrichment analysis showed that identified genes were related to cell cycle, as well as to transcriptional and translational processes. To assess the functional consequences of Dp1 DNA binding, the ChIP-Seq data were supplemented with gene expression profile of MM1S cells following shRNA-mediated Dp1 and E2F knock-downs. Integrated analysis incorporating ChIP-seq and expression data identified Dp1 response program in MM. 805 (46%) of 1752 differentially expressed genes also have binding sites for Dp1 and likely are direct transcriptional targets of Dp1 in MM. Enrichment analysis of direct targets revealed that the most strongly enriched pathways for both Dp1 and E2F1 genes combined were related to the cell cycle, especially DNA replication, repair, and metabolism. Interestingly, pathway analysis identified ''regulation of RNA metabolic processes'' (40 target genes), ''RNA processing'' (93 target genes) ''RNA splicing'' (95 genes), and ''RNA binding'' (53 genes) as statistically significant RNA-related categories enriched among Dp1 target genes, suggests role of Dp1 in RNA splicing.

Based on our previous data showing that dysregulated alternate splicing (AS) has significant impact on overall clinical outcome MM, we evaluated the expression of Dp1-modulated splicing factors in our clinically annotated cohort of MM patients and 5 normal PCs. We identified 23 SFs upregulated in MM compared to normal plasma cells. Importantly, the increased expression of 12 of these SFs was linked with poor prognosis in this cohort of myeloma patients. Our data show for the first time that SFs are upregulated in myeloma and link to clinical outcome. To evaluate the impact of Dp1 on alternate splicing (AS), we performed genome-wide analysis of alternate splicing in total RNA from Dp1 silenced MM1S cells using Human Exon1 ST arrays. Splicing profiles showed that Dp1 knock down causes widespread changes in AS. We have identified 3683 genes whose one exon has splicing index more than 1.5 in in shDP1 compared to control pLKO.1-transduced MM1S cells, suggesting impact of Dp1 silencing on alternate splicing. We are now evaluating impact of a peptide able to disrupt Dp1-E2F1 binding with consequent effect on MM cell growth and alternate splicing.

In conclusion, our investigation showed that the Dp1/E2F1 signaling pathway plays significant role in myeloma and can directly activate transcription of specific SFs with effect on alternate splicing and potential functional, clinical and therapeutic implications in myeloma.

Disclosures: No relevant conflicts of interest to declare.


BACKGROUND
Fosfomycin is an antimicrobial commonly used in uncomplicated urinary tract infections. The microbiological effectiveness of fosfomycin against nonurinary Gram-negative isolates has not been widely investigated. The aim of this study was to evaluate the in vitro activity of fosfomycin against Gram-negative nonurinary isolates in a region of Greece where considerable antimicrobial resistance has been detected.

METHODS
Data were retrieved from the microbiological library of the University Hospital of Heraklion, Crete. We retrospectively examined the susceptibility of all Gram-negative nonurinary isolates to fosfomycin, collected over 1 year (January-December 2008).

RESULTS
A total of 594 nonurinary Gram-negative isolates were examined. Susceptibility testing was performed for 270 (45.4%) Enterobacteriaceae, 209 (35.2%) Gram-negative nonfermentative bacilli and 115 (19.4%) other Gram-negative bacteria. In total, 385 (64.8%) were susceptible to fosfomycin. Specifically, all Escherichia coli, Proteus mirabilis and Salmonella species isolates were susceptible. Additionally, 73 out of 94 (77.7%) Klebsiella pneumoniae (including carbapenem-resistant strains), 22 out of 32 (68.8%) Enterobacter species and 51 out of 79 (64.5%) Pseudomonas aeruginosa isolates were susceptible to fosfomycin. Susceptibility was highest amongst isolates (45 of 61; 73.8%) taken from outpatients and lowest for intensive care unit isolates (78 of 161; 48.4%). Isolates originating from the pediatric wards exhibited higher susceptibility (45 of 63; 71.4%) than isolates originating from other departments (340 of 531; 64%).

CONCLUSION
In a region with relatively high levels of antimicrobial resistance, fosfomycin seems to exhibit good levels of in vitro activity against Gram-negative nonurinary isolates. These data justify further evaluation of its potential clinical effectiveness.


Objective: research is to study the role of L-carnitine, tumor necrosis factor α (TNF-α), and interleucine-6 (IL-6) in the development of NASH. Materials and Methods: examined 65 patients with NASH. Blood serum L-carnitine, TNF-α and IL-6 level was estimated using the enzyme-linked immunoassay method. Results: patients with NASH had a decreased blood serum level of L-carnitine. L-carnitine level was found to be in strong inverse correlation dependence on cellular damage markers, L-carnitine levels affect the performance TNF-α and IL-6. Conclusion: L-carnitine contributes to lipotoxic stress development and development of systemic liver inflammation.


ABSTRACT Porin (PorB) is a major outer membrane protein produced by all Neisseria gonorrhoeae strains and has been a focus of intense interest as a vaccine candidate. In this study, the immunogenicity of PorB in mice was investigated after several immunization regimens. Outer membrane vesicles (OMV), recombinant renatured PorB (rrPorB), and PorB-expressing Venezuelan equine encephalitis (VEE) virus replicon particles (PorB VRP) were delivered intranasally (i.n.) or subcutaneously (s.c.) into the dorsal area or the hind footpad in three-dose schedules; the PorB VRP-immunized mice were given a single additional booster dose of rrPorB in Ribi adjuvant. Different delivery systems and administration routes induced different immune responses. Mice immunized s.c. with rrPorB in Ribi had the highest levels of PorB-specific serum immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Surprisingly, there was an apparent Th1 bias, based on IgG1/IgG2a ratios, after immunization with rrPorB in Ribi in the footpad while the same vaccine given in the dorsal area gave a strongly Th2-biased response. PorB VRP-immunized mice produced a consistent Th1 response with a high gamma interferon response in stimulated splenic lymphocytes and very low IgG1/IgG2a ratios. Immunization by OMV delivered i.n. was the only regimen that resulted in a serum bactericidal response, and it generated an excellent mucosal IgA response. Serum from mice immunized with rrPorB preferentially recognized the surface of whole gonococci expressing a homologous PorB, whereas serum from PorB VRP-immunized mice had relatively low whole-cell binding activity but recognized both heterologous and homologous PorB equally. The data resulting from this direct comparison suggested that important aspects of the immune response can be manipulated by altering the form of the antigen and its delivery. This information coupled with an understanding of protective antigonococcal immune responses will enable the design of the optimal vaccine for N. gonorrhoeae.


The world's population has witnessed the concurrence of two powerful global trends: an unprecedented growth in foreign direct investment (FDI) and an increase in natural disasters. Since investment decisions are based on an evaluation of expected risks and returns, we consider whether FDI decisions are influenced by natural disasters. We do so by considering the relation between FDI in 94 countries between 1984 and 2004 and the number of disasters striking those countries. Across a variety of empirical tests that control for two-way fixed effects we find natural disasters to be negatively and statistically significantly associated with a country's FDI. (JEL Q54)


In this work, various methods for the estimation of the parameter uncertainty and the covariance between the parameters and the state variables are investigated using the local ensemble transform Kalman filter (LETKF). Two methods are compared for the estimation of the covariances between the state variables and the parameters: one using a single ensemble for the simultaneous estimation of model state and parameters, and the other using two separate ensembles; for the initial conditions and for the parameters. It is found that the method which uses two ensembles produces a more accurate representation of the covariances between observed variables and parameters, although this does not produce an improvement of the parameter or state estimation. The experiments show that the former method with a single ensemble is more efficient and produces results as accurate as the ones obtained with the two separate ensembles method. The impact of parameter ensemble spread upon the parameter estimation and its associated analysis is also investigated. A new approach to the optimization of the estimated parameter ensemble spread (EPES) is proposed in this work. This approach preserves the structure of the analysis error covariance matrix of the augmented state vector. Results indicate that the new approach determines the value of the parameter ensemble spread that produces the lowest errors in the analysis and in the estimated parameters. A simple low-resolution atmospheric general circulation model known as SPEEDY is used for the evaluation of the different parameter estimation techniques.


Organizations nowadays are confronted with changes in the global business environment that are expected to have a profound impact on them. Organizations operating in industries that rely on knowledge workers in particular, face the challenge to change and align themselves in order to meet the needs of an ever changing business environment. Knowledge workers are mostly referred to as 'talent' because their most important value and contribution is their competence. Talent is the core asset of knowledge driven organizations, and human resource departments (HR) are therefore increasingly seen as the key interface between individual internal and external talent and the organization itself.One of the most serious threats to future organizational performance is the predicted shortage of talent on a global scale. This is particularly due to drastic demographic developments, i.e. retiring baby-boomers -people born between 1946 and 1964- and decreasing numbers of highly educated people in the western world, combined with the higher-than-average economic growth in developing countries drive up the demand for talent worldwide. Therefore, multinational knowledge driven organizations must find strategies today in order to become able to attract, develop and retain talent, to make sure that they will stay on the 'winning side' of the widely predicted "war for talent".That is why managing talent is considered a crucial part of organizational performance and the concept of fostering relationships between talent both within and outside the organization is seen as the most effective means to achieve that goal. The model analyzed in this thesis is called Talent Relationship Management (TRM) and its focus is on managing the Relationships between talented people.The findings presented in this thesis derive from interviews conducted with HR managers of four different multinational enterprises operating in the industrial energy sector both in Germany and Sweden. All four organizations started to implement TRM and have been working with this strategy between two and four years. The main focus of the interviews was to learn from their experience and to answer the research question: Can Talent Relationship Management be used as the key strategy for organizational change, and if so, what are the critical factors that should be taken into account?Although TRM is also often introduced, mainly by consultancies working in the field of HR, as just another HR strategy putting emphasis on isolated issues such as for example 'employer branding' and 'campus recruiting', our findings suggest that TRM is only useful if it is implemented as a long term strategy of organizational change. This has profound impact on the internal structure and culture of the organization with implications for all individuals because all members are affected. Not only are the challenges of implementing TRM being presented in this thesis but also the critical aspects are examined. As a result three major aspects are highlighted that put the -in many cases- very optimistic and positive picture of TRM into perspective.


Epoxyeicosanoids, including the epoxyeicosatrienoic acids are signaling molecules which appear to help ameliorate the effects of a wide variety of pathological conditions. The enzyme soluble epoxide hydrolase (sEH) metabolizes these molecules by converting them to their corresponding vicinal diols. Inhibition of sEH either by knockout or chemical inhibitors increases epoxyeicosanoid levels in vivo and provides significant organ protection in models of brain, cardiac, and renal injury. sEH also appears to be involved in modulating inflammation, pain pathways, pulmonary function, hypertension, and diabetes. Potent sEH inhibitors have been developed in academic, pharmaceutical, and biotech laboratories and described in the patent and scientific literature. Most of the inhibitor scaffolds employ a urea or amide which functions as an active-site transition state mimic. Arête Therapeutics compound AR9281 successfully completed phase Ia and 1b studies. A phase IIa proof of concept trial for treatment of impaired glucose tolerance has been completed, but the results are not yet reported.


Numerous Korean tea [Camellia sinensis (L.) O. Kuntze] populations abandoned for more than nine centuries represent important genetic resources for future breeding of new tea types and tastes. This study was conducted to evaluate on the basis of random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) markers the degree and organization of genetic diversity within and between six Korea populations and to formulate conservation strategies for tea populations in Korea. Of the 50 RAPI) primers screened, 12 primers generated 25 reproducible and polymorphic bands. The genetic diversity within populations calculated from the Nei's index averaged 0.33 and was relatively lower than that found in other natural plant populations. This could be explained by the narrow genetic base of the tea samples introduced from Mainland China and considerable reduction in population size following mass destruction of tea populations in the fourteenth century. No geographical trends were observed among the tea populations following classification by unweighted pair group method and arithmetic average (UPGMA) and Nei distances and factorial correspondence analysis (FCA) carried out on individual samples. Even though highly significant differences were found among populations upon an analysis of molecular variance (AMOVA), a markedly higher proportion of diversity was observed within populations (84%) as compared with between populations (16%). The fact that most diversity is within populations reflects the highly outcrossing nature of tea species. In the light of these results, it is proposed that conservation efforts target whole diverse populations rather than selected individuals from different populations. Due consideration should nevertheless be given to populations comprising private or rare alleles.


First line host defense against virus attack includes the innate immune system which recognizes and mounts rapid antiviral responses. An important aspect in defense against viral infections is the production of type 1 interferon which provides a protective state to surrounding cells. TBK1 is a critical kinase involved in cellular transcriptional responses to infection and production of type I interferon. We found that TBK1 undergoes Lys63 ubiquitination following viral infection. The E3 ligases Mindbomb 1 (MIB1) and Mindbomb 2 (MIB2) associate with the TBK1 complex and confer K63-linked ubiquitin to TBK1, resulting in activation of downstream IRF signaling. Two lysine residues on TBK1 are ubiquitin acceptor sites and critical for innate antiviral defense. Ectopic expression of MIB1 or MIB2 augments TBK1-induced antiviral responses. Deficiency of MIB1 and MIB2 demonstrates that these genes are critical for TBK1 ubiquitination, type 1 interferon production, and TBK1-mediated antiviral activity. These results identify MIB1 and MIB2 as positive regulators of antiviral responses through polyubiquitination of TBK1.


Die castings generally contain a large quantity of porosities due to the entrapment of air or gas in molten metal during mold filling. Although the entrapped air or gas is compressed by high casting pressure during pressurization, it will eventually remain in the castings as defects after solidification. Therefore, it is important to clarify the relation between the volume of gas defects and the pressure applied to the molten metal so as to optimize the casting design.In this study, we investigated the compression behavior of entrapped gas during casting. We determined the volume of gas defects and gas content in die castings by density measurement and vacuum fusion extraction method respectively. Then we calculated the gas pressure in the defects from the above volume of defects and gas content, and compared with the die casting pressure. The calculated gas pressure in the defects was found to be not equal to the die casting pressure, but equal to the pressure of the molten metal just before it dropped abruptly due to the complete blocking of the liquid metal channel by solidification. From the experimental results, the behavior of the entrapped gas can be inferred as follows. Immediately after the mold was filled with molten metal, the entrapped gas was instantly compressed. After that, the pressure of molten metal decreased gradually with the progress of solidification of the molten metal channel, and the volume of entrapped gas increased correspondingly until the pressure of the molten metal dropped abruptly. Then the volume of the entrapped gas showed a slight expansion equal to the solidification shrinkage of the enclosed molten metal.The above inference was verified by measuring the volume of the entrapped gas defects in castings made with intentional depressurization carried out at the time when mold filling just finished or halfway through the solidification of the molten metal channel.


This paper presents a system stability analysis of a grid-connected inverter from a linear system viewpoint. A Photovoltaic (PV) inverter model is derived using a system identification method, specifically the Hammerstein-Wiener model. The PV inverter is supplied by a controllable DC power supply and the inverter output is connected to a 220 V utility grid. The input and output characteristics on the inverter terminals are collected and the nonlinear model of the inverter is obtained. The inverter model is decomposed into three parts follow as nonlinear input, linear middle part and nonlinear output. Both nonlinear parts are deemed static where the dynamical behavior is described by the middle part. The stability of the inverter is analyzed based on a linearized model of the nonlinear system. Frequency response analysis is performed for insight on the system dynamical behavior.


For many of the world's poor people, adaptation to climate change is not a choice but a reality. Existing evidence suggests that the poor, particularly those in the developing world, are the most vulnerable to any changes in climate variability and change. Using research methods inspired by the tradition of participatory research, we explore and discuss community perceptions on climate change adaptation governance in South Africa. We examine the myriad ways in which climate change adaptation policies and strategies are developed, and we systematically discuss the factors which either facilitate or hamper the involvement of all stakeholders in the development of these intervention measures. Our findings indicate that women seem to be the group of people who are mostly unaware of community initiatives, policies, and strategies for the adaptation to climate change. Thus, it is argued that, although South Africa has developed good climate change initiatives, policies, and strategies, the implementation of these policies seems to present difficulties, as those for whom they have been developed do not seem to have any knowledge of their effectiveness in helping them build resilience against extreme weather events. This study recommends that, in order to achieve successful public participation in climate change adaptation policy development, there must be an all-inclusive system which incorporates all stakeholders, including vulnerable groups.


For decades, one of the most significant challenges in vehicular traffic networks has been how to mitigate traffic congestion characterized by increased vehicle queueing and slower traffic speeds. Whereas traffic congestion is a complicated and subjective matter, congestion delay consists of recurrent delay and non- recurrent delay. Recurring congestion is attributed to high excess demand that constitutes about half of congestion delay, and most of the rest is non-recurring congestion mainly occurring due to incidents. In order to reduce congestion more effectively in vehicular traffic networks, it is necessary to focus on how to control high utility demand for using traffic systems and how to guarantee safety against incidents by using various strategies, instead of inefficiently widening roads. Therefore, this dissertation provides diverse approaches to improve system throughput as well as to enhance collision safety for vehicular traffic networks through understanding of vehicular traffic flow, ramp-metering control, traffic safety metric, and inter-vehicle velocity control. In Chapter 2, we provide a macroscopic traffic flow model called a time-gap-based traffic model, which is a good and simple representative model for vehicular traffic flow. The proposed time-gap-based traffic model is well validated with empirical traffic data using least squares matching and is consistent with previous research outcomes about propagation velocity. Moreover, two analysis techniques to estimate the time gap from traffic measurement data are suggested. Chapter 3 presents two optimal coordinated ramp-metering algorithms based on the time-gap-based traffic model defined in Chapter 2. The purpose of the two optimization problems is to attain the maximum average system capacity for vehicular traffic networks. In addition, both of them are coordinated ramp- metering strategies that make use of the measurement data along a highway corridor to control all metered ramps simultaneously. One is a steady-state optimization problem used under supposition when the traffic system reaches a steady-state, whereas another optimal control is a time- variant optimization problem exploited when the traffic flow changes continuously with respect to time. The time- variant optimization problem considers an on-ramp queue management strategy. We propose a traffic safety metric called a safety marginal value (SMV) to be applied to continuous-space and discrete-time vehicular traffic networks in Chapter 4. The SMV represents the safety level of collision risk at every time step and is bounded by two non-negative integers. However, the computational complexity in determining the SMV grows dramatically, particularly when the number of vehicles traveling on a roadway increases. Hence, a finite space horizon for the SMV is also developed in order to prune the computational complexity of our proposed traffic safety indicator. A safety analysis of a car-following model is conducted with the SMV and with a microscopic traffic simulation. A car- following model called a target time-gap-based velocity update model is proposed in Chapter 5. Our proposed microscopic traffic flow model is used for inter-vehicle velocity control, which every vehicle exploits in order to refresh the velocity and position for the next time step. The microscopic traffic simulation results are matched well with empirical traffic data. Thus, the target time- gap-based velocity update model is considered a representative car-following model that can accurately mimic typical driving behavior. The effective domains of the target time gap and the update time interval, which guarantee both collision-free movement of all vehicles and system capacity enhancement compared to the traffic data measured in the field, are examined


THE THIRTY-FIFTH TECHNICAL SESSION of the Rochester Mineralogical Symposium was held on 20 April 2018. Abstracts were reviewed by a committee consisting of Dr. Steven Chamberlain, New York State Museum; Dr. Carl Francis, Maine Mineral & Gem Museum; Dr. Sarah Hanson, Adrian College; Dr. Marian Lupulescu, New York State Museum; and Dr. George Robinson, St. Lawrence University. Nine abstracts were submitted, accepted, and scheduled for platform presentations on Friday afternoon. The abstracts follow.


PMBLDC motors are gaining a lot of popularity due to their high efficiency as the Permanent Magnets do not carry current which results in negligible copper losses as compared to asynchronous motors. This paper introduces a design for speed control of the PMBLDC motor using multilevel dc link inverter fed by a Boost Converter. The multilevel dc link inverter consist of five level voltage sources, which are controlled by switches. The motor can be driven at different speed level as per its load requirement by making use of five level MLDC Link Inverter. In case of traditional inverter which is only a one level inverter the speed cannot be controlled as per the load requirement. The MLDC link inverter provides the output voltage waveform in step shape form. Thus as the number of cells (n) increases output voltage touches the fundamental component. The input voltage is low, thus to increase the input voltage given to the MLDC link inverter the (Boost Converter) has been designed. The Boost Converter is placed in between (DBR)Diode Bridge Rectifier and (MLDCLI). Both the design and results of Single level inverter and Multilevel Dc Link Inverter are obtained and compared by using the MATLAB Software along with the use of Simulink and Simpower system Tools.


The Food and Agricultural Organization (FAO) of the United Nations is conducting a global assessment of tropical forest resources, which will be accomplished by mid-1992. This assessment requires, in part, estimates of the total area of tropical forest cover in 1990 and the rate of change in forest cover between 1980 and 1990. The following are described here: (1) the strategic process used to select the statistical and remote sensing methods that accomplish this objective, (2) general details and expected precision of the selected method, and (3) recommendations for monitoring and assessment actions after mid-1992.


The authors define and approximately solve the problem of unsupervised image sorting that is considered as a kind of content-based image clustering. The content-based image sorting is the creation of a route that passes through all the images once, in such an order that the next one from the previous image has similar content. In the end, an image ordering (e.g. slideshow) is automatically produced, so that the images with similar content should be close to each other. This problem resembles the problem known in the literature as 'travelling salesman problem' (TSP). In this work, the authors have proposed two classes of methods (the nearest-neighbour and genetic methods) that have also been applied on the TSP problem. Their benefits on computational efficiency and accuracy are discussed over six datasets that have been created from the GHIM-10K dataset. The experimental results demonstrate that the proposed methods efficiently solve the image sorting problem, producing image sequences that almost agree with human intuition.


Purpose It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms. Materials and methods The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot. Results Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1. Conclusion Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.


Use of silicone derivative and onion extract had been reported in the prevention of hypertrophic scarring. Our experience showed the preventive use of silicone derivative plus onion extract gel on hypertrophic scars after median sternotomy. In a randomized, double blinded, placebo‐controlled study, 60 patients after median sternotomy incisions were separated into two groups. All patients were treated either with silicone derivative plus onion extract gel (Cybele® scagel) or placebo gel twice daily for a total treatment period of 12 weeks. During each visit, pain and itching scores were graded by the patients and scar characteristics were observed by surgeons using the Vancouver scar scale. Pain and itch score values from patients' who applied silicone derivative plus onion extract gel was less than another group (P < 0·05). Pigmentation was significantly different between two groups (P < 0·05) and the reduction of scores on vascularity, pliability, height in treated group was not superior to the untreated group. No adverse events were reported by any of the patients. A silicone derivative plus onion extract gel is safe and effective for the preventing the hypertrophic scarring after median sternotomy.


OBJECTIVE
The DSM-IV classification of personality disorders has not proven satisfying to either researchers or clinicians. Incremental changes to categories and criteria using structured interviews may no longer be useful in attempting to refine axis II. An alternative approach that quantifies clinical observation may prove useful in developing a clinically rich, useful, empirically grounded classification of personality pathology.

METHOD
A total of 496 experienced psychiatrists and psychologists used the Shedler-Westen Assessment Procedure-200 (SWAP-200) to describe current patients diagnosed with axis II personality disorders. The SWAP-200 is an assessment tool that allows clinicians to provide detailed, clinically rich descriptions of patients in a systematic and quantifiable form. A statistical technique, Q-analysis, was used to identify naturally occurring groupings of patients with personality disorders, based on shared psychological features. The resulting groupings represent an empirically derived personality disorder taxonomy.

RESULTS
The analysis found 11 naturally occurring diagnostic categories, some of which resembled current axis II categories and some of which did not. The findings suggest that axis II falls short in its attempt to "carve nature at the joints": In some cases it puts patients who are psychologically dissimilar in the same diagnostic category, and in others it makes diagnostic distinctions where none likely exist. It also fails to recognize a large category of patients best characterized as having a dysphoric personality constellation. The empirically derived classification system appears to be more faithful to the clinical data and to avoid many problems inherent in the current axis II taxonomy.

CONCLUSIONS
The approach presented here may be helpful in refining the existing taxonomy of personality disorders and moving toward a system of classification that lies on a firmer clinical and empirical foundation. In addition, it can help to bridge the gap that often exists between research and clinical approaches to personality pathology.


Back ground: Gingiva as other part of oral cavity has been effected with hereditary diseases. When navigate in the jungle of gingival disease hereditary gingival fibromatosis will appeared as vague hereditary condition and the pathogeneses of disease is not clearly understood.  Clinically it's characterized by massively increasing in gingival tissue mass, which appeared more fibrous.  Transforming growth factor beta 1 (TGF-β1) is growth factor which had critical role in pathogeneses of (HGF) together with interferon gama (IFN-γ) which inflammatory cytokines the level of these cytokines may be changed according to gender, age or site distribution (generalized, localized). Aim:  To evaluate the level of TGF-β1and IFN-γ immunohistochemically in hereditary gingival fibromatosis according gender, age and site distribution. Methods: Immunohistochemistry for detection of TFG-β1 and IFN-γ in paraffin embedded tissue sections for 17 blocks of hereditary gingival fibromatosis. Result: Non-significant difference of TGF-β1 according to gender, age and site in .Also Non- significant difference of INF -γ according to gender and site. On other hand significant difference of INF-γ according to age. Conclusion: Age, gender and site have no effect on expression of TGF-β1 in hereditary gingival fibromatosis; same findings were for IFN-γ except the age which has an obvious effect on IFN-γ expression. Keywords: Hereditary Gingival Fibromatosis.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Background: Unlike Japanese gastric cancer, the majority type of Thai gastric cancer caused poor prognosis; especially poorly differentiated, signet ring cell histologic type that is predominant in nearly 70 percent of gastric cancer population. The detection of high mRNA IL-8 expression level independently related to poor prognostic histologic type in our recent study. We aim to study adjuvant or neo-adjuvant chemotherapy, and IL-8 mRNA expression level to predict the survival rate after treatment.

Method: The prospective study gastric cancer therapy was conducted in 170 new advances gastric cancer cases. The authors recruited only stage III and IV of 111 cases. Adjuvant chemotherapy was completely administration in 68 patients. For the group of neo-adjuvant therapy, FOLFOX IV regimen and others were administrated in 43 patients who had unresectable tumor and underwent enteric access procedure to before chemotherapy treatment. IL- 8 mRNA expression level was tested before chemotherapy treatment. Chi-square test, log rank test, and Kaplan Meier survival curve were used for qualitative and quantitative data analysis (STATA10.0, USA), and p value<.05 is reported statistically significant. Result: Demographic data was described and divided adjuvant therapy, 68 patients, in to 2 groups by two chemotherapy regimens of 5-Fluouracil (5-FU) based combined with cytotoxic drug. The Age, sex, smoking, drinking, disease stage, histology, tumor position, type of operation, percent of positive node were reported as no statistically significant differences in 2 groups. The total means number of lymph node taken off is 11.96±11.48 and 24.62 ±16.48 nodes, respectively and there is no statistically significant. For the Adjuvant therapy, the overall survival rate in 2 groups is not reach statistical significant difference at 45 months. However, toxicity occurred in Cisplatinum with 5- Fluouracil( Cis-FU) more than FOLFOX IV regimen with clinically significant by anemia and neutropenia those need treatment, but no death related toxicity of chemotherapy. Kaplan Meier of overall survival curve treatment has not demonstrated difference between 2 regimens. However, for the neo-adjuvant therapy group, overall survival has reach 40 months and 75 percent of population is still survived in group of high expression. The patients who had IL-8 expression level Raw RQ more than 100, or log10 more than 2 have trend to have prolong median and overall survival than patient who had low expression, although there is not statistically significant difference.

Conclusion: The improvement of treatment result by neo-adjuvant therapy by FOLFOX-IV regimen. The higher IL-8 mRNA expression level of Raw RQ more than 100, or log 10>2 demonstrated in prolong survival in group of neo-adjuvant therapy who response to the treatment.

Citation Format: Sirikan Yamada. The survival prediction after curative resection with adjuvant chemotherapy and neo-adjuvant chemotherapy in locally advance stage by gastric mucosal IL-8 mRNA expression for Thai gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4257. doi:10.1158/1538-7445.AM2014-4257


We have measured the activity of S‐adenosyl‐L‐methionine synthetase, the ratio between the high‐ and low‐molecular‐weight forms of this enzyme and the concentration of S‐adenosyl‐L‐methionine in liver biopsies from a group of controls (n = 6) and in six cirrhotics (five posthepatitic and one alcoholic). The total activity of S‐adenosyl‐L‐methionine synthetase was markedly reduced in cirrhosis (37.5% of that found in the control group). This was due to a specific reduction in the high‐molecular‐weight S‐adenosyl‐L‐methionine synthetase in the group of cirrhotics (73.9 pmoles per min per mg protein) when compared with that observed in controls (460.3 pmoles per min per mg protein). Despite this reduction in the rate of synthesis of S‐adenosyl‐L‐methionine (the high‐molecular‐weight form of the enzyme is 15 times more active than the low‐molecular‐weight form at physiological concentration of substrates), the concentration of this metabolite was the same in the control group (17.3 ± 2.6 μM) and in the group of cirrhotics (17.8 ± 3.1 μM). To explain these findings, it is postulated that in human liver, where the concentration of S‐adenosyl‐L‐methionine is lower than the Km values of a variety of enzymes that use this metabolite (around 50 to 100 μM), a reduction in the synthesis of S‐adenosyl‐L‐methionine is compensated by a reduction in the rate of utilization of this molecule without affecting the intrahepatic concentration of S‐adenosyl‐L‐methionine. This postulate was tested by decreasing the activity of the high‐molecular‐weight S‐adenosyl‐L‐methionine synthetase in rat liver by treatment with galac‐tosamine. In the rat liver, the concentration of S‐adenosyl‐L‐methionine is about 100 μM. Galactosamine treatment reduced the high‐molecular‐weight S‐adenosyl‐L‐methionine synthetase from 66.5 pmoles per min per mg protein in the control group (n = 9) to 31.4 pmoles per min per mg protein (n = 8). This reduction of the activity of the high‐molecular weight S‐adenosyl‐L‐methionine synthetase was accompanied by a reduction of the concentration of S‐adenosyl‐L‐methionine from 111.3 ± 5.7 μM in the control group to 56.9 ± 3.2 μM in the group of animals treated with galactosamine. Our results support the hypothesis that in human cirrhotic liver there is a marked reduction in the rate of synthesis and utilization of S‐adenosyl‐L‐methionine.