Supplemental Digital Content is available in the text. Background: Medication overlap leading to medication excess is a form of therapeutic duplication, itself a type of potentially inappropriate prescribing. Objective: To determine the prevalence of potential medication excess in the Veterans Health Administration (VHA) and identify associated medication-level, patient-level, and system-level factors. Research Design: A retrospective database study. Subjects: All veterans who received ≥1 prescription dispensed by a VHA pharmacy in fiscal year 2014. Measures: The primary outcome of "medication excess" was defined for each patient as the number of excess days' worth of medications for all overlap episodes (concurrently dispensed medications with the same name for >10 d). Predictors included medication-level, patient-level, and system-level factors. Multivariable negative binomial regression analyses estimated the rate ratio of each predictor with medication excess. Results: Among 4,687,453 veterans, 64% had ≥1 medication overlap episodes. Patients were prescribed a median of 7 [interquartile range (IQR), 3–12] unique medications, had a median of 2 (IQR, 0–5) overlap episodes, and a median of 27 (IQR, 0–96) days of medication excess. In adjusted regression models, factors associated with greater risk of medication excess included having more comorbidities, multiple prescribers, a combination of filling locations (consolidated mail-order pharmacy vs. local pharmacy), and multiple prescription durations (≥90 d vs. less). Conclusions: Medication excess was high among VHA users, with nearly two-thirds of patients experiencing at least 1 duplicative medication. As systems such as mail-order pharmacies and 90-day supply are increasingly implemented to reduce costs and improve medication adherence, it is important to recognize the potential for systems-level inefficiencies and potentially inappropriate prescribing.


Auditory pattern recognition by the CNS is a fundamental process in acoustic communication. Because crickets communicate with stereotyped patterns of constant frequency syllables, they are established models to investigate the neuronal mechanisms of auditory pattern recognition. Here we provide evidence that for the neural processing of amplitude-modulated sounds, the instantaneous spike rate rather than the time-averaged neural activity is the appropriate coding principle by comparing both coding parameters in a thoracic interneuron (Omega neuron ON1) of the cricket (Gryllus bimaculatus) auditory system. When stimulated with different temporal sound patterns, the analysis of the instantaneous spike rate demonstrates that the neuron acts as a low-pass filter for syllable patterns. The instantaneous spike rate is low at high syllable rates, but prominent peaks in the instantaneous spike rate are generated as the syllable rate resembles that of the species-specific pattern. The occurrence and repetition rate of these peaks in the neuronal discharge are sufficient to explain temporal filtering in the cricket auditory pathway as they closely match the tuning of phonotactic behavior to different sound patterns. Thus temporal filtering or "pattern recognition" occurs at an early stage in the auditory pathway.


Abstract Practitioners can draw upon a body of literature on various aspects of managing digital archives. However, one area where guidance is lacking is cataloguing. The characteristics of digital material have brought into question basic cataloguing practices. This article considers the treatment of the cataloguing of digital material in the archival literature. It focuses on discussions of the implications for descriptive standards of digital records, and considers the solutions proposed in the literature or adopted by practitioners. Through tracing discussions of cataloguing through the literature, this article surveys how current descriptive practice has been applied to digital material. Locating these discussions within a wider context of technological change, affecting not only archival material but also the environment within which it is used, the article explores the profession's response to the demands of digital material and identifies areas for further research.


The design and development of a new magazine receptacle which reduces time and effort for operation will benefit Defence capability at the individual and unit levels. This paper covers the background, the reloading sequence and current magazine storage equipment. Following this, the paper evaluates the magazine pouch, explores the design and development of a magazine dispenser and compares the two. Finally the paper concludes how the magazine dispenser concept provides a means to reload quicker and easier in comparison with the magazine pouch.


The purpose of this study is to test and prove empirically the existence of correlations between variables of regional taxes, population, economic growth and regional expenditure. The problem in regional revenue (PAD) in Banjarnegara District which is not in accordance with the target set even the income is less than the target set in the previous year. The subject of this study is the Regional Financial and Asset Revenue Management Agency (BPPKAD) of Kabupaten Banjarnegara with an object of financial statements containing regional income, regional expenditure, regional tax, and gross regional domestic income (GRDP). In addition, researchers also use data on the number of population included in the productive age category, the data obtained through the official web of the Central Statistics Agency (BPS) of Banjarnegara Regency. This study uses qualitative methods with secondary data retrieval. Sampling in this study using purposive sampling. The analiss method used in this research is descriptive study. The application to process data in this study uses SPSS v.15.0. The research model used is multiple correlation, where the test aims to find correlations or relationships between two or more variables. Furthermore, the researchers also used the value for money (VFM) method to analyze the PAD owned by the Banjarnegara Regency government. The value for money method has three criteria, namely, efficient, effective and economical (3E).


We review the discovery of a new phase BN (named Q-BN) which has been created by nanosecond laser melting in the super undercooled state and quenching rapidly with rates exceeding several billion degrees per second. This phase, sequel to our earlier discovery of Q-Carbon, has amorphous structure from which phase-pure c-BN is formed in the form of nanodots, microcrystals, nanoneedles, and microneedles. Large-area single c-BN are formed by providing a template for epitaxial growth during quenching of super undercooled liquid BN. Since there is a rapid crystal growth from liquid, both n- and p-type dopants can be incorporated into electrically active substitutional sites with concentrations exceeding solubility limits through the phenomenon of solute trapping. We have grown diamond on c-BN by pulsed laser deposition of carbon at 500°C without the presence of hydrogen, and created c-BN and diamond epitaxial composites. We discuss the mechanism of epitaxial c-BN and diamond growth on lattice matching c-BN template under pulsed laser evaporation of amorphous carbon. This discovery on direct conversion of h-BN into phase-pure c-BN at ambient temperatures and pressures in air, represents a seminal contribution to the field of boron nitride, which is quite complementary to our discovery of graphite to diamond conversion. We have bypassed thermodynamics with the help of kinetics and time control. This research represents a major breakthrough for c-BN and diamond based high-power electronic and photonic devices, and host of other applications related to high-speed machining, deep-sea drilling, field-emission displays and biomedical applications.


Integrated Library Systems are adopted by libraries in order to meet the ever changing needs of their users and make the library staff more efficient and effective in conducting their work on a daily basis. In recent years' libraries have made huge investments in acquisition of these systems. This study has established the effects of integrated library systems' (ILS) performance of the Post Modern Library of Kenyatta University, Kenya. Empirical literature indicates the link between the library system and performance of its patrons, staff and other stakeholders. The study empirically analyzed the effect of usability of the library system on performance of the postmodern library of Kenyatta University, Kenya. The study used Technology Acceptance Model. The research design was descriptive cross sectional approach. The target population was 176 system users comprising of 56 library staff members from the Post Modern Library of Kenyatta University who work with the system on a daily basis, 60 students; 30 at postgraduate level and 30 students at undergraduate level. The study was guided by primary data collected using structured questionnaires and secondary data obtained from the integrated Library System used by the Kenyatta University Post Modern Library. The analysis of collected data was grounded on descriptive and multiple regression analysis. The study concluded that the KU postmodern library's system had better usability features, included guidelines, usability testing and ease of use. The study recommends that the library management should also put in place strict measures to control access to the system avoid data loss tampering or even manipulation.


Current robotic haptic object recognition relies on statistical measures derived from movement dependent interaction signals such as force, vibration or position. Mechanical properties that can be identified from these signals are intrinsic object properties that may yield a more robust object representation. Therefore, this paper proposes an object recognition framework using multiple representative mechanical properties: the coefficient of restitution, stiffness, viscosity and friction coefficient. These mechanical properties are identified in real-time using a dual Kalman filter, then used to classify objects. The proposed framework was tested with a robot identifying 20 objects through haptic exploration. The results demonstrate the technique's effectiveness and efficiency, and that all four mechanical properties are required for best recognition yielding a rate of 98.18 $\pm$ 0.424 %. Clustering with Gaussian mixture models further shows that using these mechanical properties results in superior recognition as compared to using statistical parameters of the interaction signals.


Several semiempirical models for peptide electrophoretic mobility have been tested for capillary electrophoresis (CE) separation with a positively charged capillary using on‐line CE combined with electrospray ionization‐mass spectrometry (ESI‐MS). In the current system with pH 2.7, the expression q/M0.56 provided the best correlation with the electrophoretic mobility in the analysis of a set of 18 standard samples, where q is the calculated net charge and M is the molecular weight. The peptides resulting from various digests of horse heart myoglobin or bovine hemoglobin were used to demonstrate the validity of this correlation. Post‐translationally modified peptides from tryptic digest of human myelin basic protein were also investigated and were found to provide excellent correlation with the linear plot when the total charge of the peptide was correctly calculated. If the total charge was not properly calculated then the post‐translationally modified peptides fell off the linear plot. Using this method five arginine residues (residues 5, 49, 54, 97 and 130) were found to be partially citrullinated, four glutamine residues (residues 8, 103, 121 and 147) were found to be partially deamidated and both methionines at residues 21 and 167 were found to be partially oxidized. Three peptides were found with phosphorylation; TPPPSQGK (residue 98 to 105), FSWGAEGQR (residue 114 to 122), and SGSPMAR (residue 163 to 169) and Arginine at 107 was found to be partially monomethylated or dimethylated. The method may provide an excellent means of identifying the presence of peptides with post‐translational modifications in conjunction with MS.


It is a puzzling fact that PCO2 in the superficial renal cortex is much higher than in renal venous blood. Using a newly developed PCO2 electrode, the authors found the highest level of PCO2 in the first portion of the proximal tubule and concluded that this peak is caused by rapid bicarbonate reabsorption in this part of the tubule. To account fully for the large elevation in cortical PCO2, they postulate a countercurrent CO2 exchange between the arteries and veins in the kidney.


The biggest challenge North Korea currently faces is to develop its agriculture to mitigate persistent food shortages. South Korea has increased its agricultural assistance toward the North since North Korea initiated its agricultural development program in 1999. Between 1995 and 2004, the South Korean government and NGOs` assistance to North Korea totaled $1,161 million, which is 35% of the international community`s total assistance to North Korea. The agricultural development projects conducted in North Korea by the international community have resulted in positive outcomes. International development projects for North Korea follow a very systematic process of planning, implementation, problem recognition, and post evaluation. In response to North Korea`s request for changing the direction of assistance from humanitarian assistance to development-oriented, it is needed to strengthen our assistance system.


These notes develop an approach for characterizing uncertainty in sequences of observable variables. Unlike traditional analyses, observations are not treated as samples from associated random variables. Instead, they are simply assumed to be quantities that satisfy sets of loose constraints. Their exact values remain uncertain and are immaterial to the derived results. When required, additional structural assumptions are introduced by associating these sequences with the state-to-state transitions of conventional finite state machines.


Although leadframe assemblies have been well developed and plastic encapsulation has been popular and common for semiconductor packaging, lots of related problems still exist in the packages. During molding process, viscous epoxy molding compound (EMC) flows over wires and drags them for a short distance, then induces the well-known wire sweep problem. Similar phenomena can also happen to the leads of a leadframe and make them shift. The lead deflection phenomena were rarely mentioned or discussed before. However, extreme deflection for one lead could be sufficiently severe to cause leads contact and damage the device. A numerical simulation was developed to predict the lead deflection of a leadframe assembly which was encapsulated with EMC after molding process. X-ray detection of the encapsulated leads and optical microscope inspections of the encapsulated leads, were introduced to investigate and verify the lead shifting phenomenon. The experimental results showed satisfactory consistency with the simulation. The deflection of the leads was calculated by applying the distributed pressure from fluid onto the exterior surface of the leads. The distributed pressure of the flowing compound during encapsulation was obtained from a 3-D flow simulation. Experiments were conducted to obtain proper properties of materials for the flow and deflection simulation. Some key parameters such as package thickness, gate shape and down-set distance were studied to evaluate their effects on the deflection of the leads. It was found that the flow effect of the EMC during molding did play an important roll for the lead deflection and should be carefully considered when designing the leadframe. The results also showed that the approach proposed in tins research did provide a useful tool for the leadframe design engineers to avoid the lead deflection problems during encapsulation.


A case of verrucous carcinoma with a focus of cytologically malignant squamous-cell carcinoma is presented. This usually occurs following radiation therapy of the verrucous carcinoma, but may rarely occur de novo, as in this case. The potential usefulness of fine-needle aspiration in detecting focal anaplasia in verrucous carcinoma is discussed. This technique may be especially useful if the lesion is to be destroyed cryosurgically.


A spherical-harmonics expansion method is used to find an approximate numerical solution of the Boltzmann transport equation (BTE) in a 1-D semiconductor device including acoustic and optical phonon, ionized impurity, and impact ionization scattering as well as a system of nonparabolic bands fitting the experimental density of states up to 2.6 eV. The method is applied to the simulation of a 1-D BJT and to the computation of the collector current multiplication factor. A comparison with experimental data is presented. >


This study aimed to investigate creativity's influence on psychological well-being, due to identified contradictions in predominantly quantitative previous research. For a greater understanding, a phenomenological qualitative design has been used. Reflecting Ryff's (1989) Scale of Psychological Well-being within semi-structured interviews, data was collected from 11 art students from the University of Bedfordshire. Inductive thematic analysis revealed the following themes: Creative compass, Social Interactions, Volition, Perceived achievements and self-attitude, Self-efficacy and lifestyle. Positive implications have been found on all dimensions of psychological well-being, apart from autonomy. The qualitative method of enquiry has allowed for an exploration of this effect and of further observations. Finally, it's been recommended that future research could use a more diverse sample when exploring the topic.


Non-isothermal modes of branching-chain reactions are analysed. Characteristic features of these reactions caused by the simultaneous action of the reaction chain avalanche and self-heating are considered in terms of concepts of the modern theory. New data are presented indicating that chain branching is the predominant factor in gas combustion processes not only at very low pressures, as it was assumed earlier, but also at atmospheric and higher pressures. The specific character of the temperature dependence of the rate of chain reactions and data dealing with the discovery of a special chain combustion mode, chain thermal explosion, are considered. The efficiency of chemical control of chain combustion in any mode including explosion, flame propagation and its transition to detonation by virtue of highly efficient non-corrosive inhibitors is demonstrated. The bibliography includes 135 references.


This article describes the use of rapid cycle improvement in a community hospital adult cardiac surgery program. The hospital participated in the Breakthrough Series: collaborative adult cardiac surgery sponsored by the Institute of Healthcare Improvement (IHI). As a result of this 1-year project, median length of stay for diagnosis-related groups 104 through 108 was decreased 30 percent from 8.62 days to 6.0 days; percentage of patients extubated within 6 hours postoperatively rose from 5 percent to 75 percent; median cost per case declined $19 percent; and pain and anxiety, service, and satisfaction scores all improved. There was no adverse impact on the clinical indicators 30-day readmission rate, reintubation, return to operating room, and mortality.


We present a model that allows the theoretical description of three-dimensional particle movement of magnetically susceptible particles in a continuously operating two-wire high-gradient repulsive-mode magnetic separator (RMMS) under laminar flow conditions. From the calculated trajectories, separation efficiencies can be determined by a statistical approach. We compare the model to experiments on a lab-type RMMS and synthetic magnetite in water.


Optimizations aimed at improving the efficiency of on-chip memories are extremely important. We propose a compiler-controlled dynamic on-chip scratch-pad memory (SPM) management framework that uses both loop and data transformations. Experimental results obtained using a generic cost model indicate significant reductions in data transfer activity between SPM and off-chip memory.


−Lean burn is an effective way to improve spark ignition engine fuel economy. In this paper, the combustion and emission characteristics of a lean burn natural gas fuelled spark ignition engine were investigated at various throttle positions, fuel injection timings, spark timings and air fuel ratios. The results show that ignition timings, the combustion duration, the coefficient of variation (COV) of the indicated mean effective pressure (IMEP) and engine-out emissions are dependent on the overall air fuel ratio, spark timings, throttle positions and fuel injection timings. With the increase of the air fuel ratio, the ignition delays and combustion duration increases. Fuel injection timings affect ignition timings, combustion duration, IMEP, and the COV of the IMEP. Late fuel injection timings can decrease the COV of the IMEP. Moreover, the change in the fuel injection timings reduces the engine-out CO, total hydrocarbon (THC) emissions. Lean burn can significantly reduce NOx emissions, but it results in high cyclic variations.


THE MAGNETIC PROPERTIES OF THE HEMATITE (α-Fe2O3) NANORODS By Samar A Ghopry, Master of Science in Physics/Applied Physics A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physics/Applied Physics at Virginia Commonwealth University. Virginia Commonwealth University, 2014. Major Director: Dexian Ye, Assistant Professor, Department of Physics At this study three samples of hematite nanorods were deposited on the silicon substrates with different varieties of glancing angle deposition techniques. One sample (S1) was prepared by using thermal deposition with partially ionized beam (PIB) and substrate rotation. The second sample (S2) was synthesized by using thermal deposition with PIB and no substrate rotation. The third sample (S3) was obtained by using E-beam deposition, PIB and rotating substrate. In addition, one sample of magnetite nanorods (S4) has been prepared in order to compare the magnetic properties of the two different iron oxides. S4 was prepared by using thermal deposition and fixed glancing angle deposition, but no PIB was applied. The hysteresis loop has been studied for all samples


Description Clevudine is an antiviral drug for the treatment of hepatitis B. Target: HBVClevudine is a nucleoside analog with an unnatural beta-L configuration. Clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels [1]. Clevudine showed a potent antiviral response, and its effect was higher in HBeAgnegative patients, with rapid viral load reduction after therapy. However, long-term therapy for more than 1 year resulted in the development of considerable resistance and myopathy. Therefore, we should consider alternative antiviral agents if clevudine resistance or clevudine-induced myopathy is developed in patients on clevudine for the treatment of CHB [2].


In GaP:N (Zn,Te) light emitting diodes electroluminescence and photoluminescence have been excited at 4.2K by a Q-switched CO2 laser and a pulsed N2 laser, respectively. In the luminescence spectral transitions of free holes to bound donor states could be identified, being responsible for the fast radiative decay on a nanosecond timescale.


The recent global recession has had differing effects on wages across Europe. This paper presents wage patterns for EU countries since the impact of the financial crisis, and compares them to previous trends. Wages in the countries hardest hit by the recession have underperformed when compared to past developments. The role of wages in determining international competitiveness is also examined and the importance of the general price level as opposed to wage levels is highlighted.


The muonic component of extensive air showers (EAS) contains information about the mass composition of cosmic rays and hadronic interactions occurring early in the EAS development. While propagating through the atmosphere, muons lose a small fraction of their energy and deviate little from a straight-line trajectory, retaining information about their production points. It is, therefore, possible to reconstruct the Muon Production Depth (MPD) from the arrival time and position of muons measured by ground arrays of cosmic-ray observatories. The estimation of the kinematic delay, a quantity directly related to the energy of muons, is key for the MPD reconstruction. The existing kinematic delay parametrization, tailored to showers with zenith angles 𝜃 ∼ 60 ◦ and muons arriving far from the shower core, represents the dominant contribution to the method's systematic uncertainties. In this contribution, we extend the MPD reconstruction to showers with 𝜃 < 60 ◦ while considerably reducing the present radial cut and applying it to energies between the second knee and ankle of the cosmic-ray spectrum, where overlap with the nominal energy at the LHC exists. To filter out the electromagnetic component of EAS, we select muons energetic enough to reach underground detectors. We use Gradient-Boosted Decision Trees, a machine learning algorithm suited for structured, heterogeneous datasets, to reconstruct the MPD. We report an unbiased MPD reconstruction (< 10 g cm − 2 ), with a muon-by-muon resolution of ∼ 80 ( ∼ 170) g cm − 2 for 𝜃 = 0 ◦ (60 ◦ ) showers. The method's applicability to higher energies and different primary species is also investigated.


A new method using an image processing system developed in our laboratories is used to measure the pore size in Mersilene, Marlex, and Teflon surgical meshes. All three meshes appear to have sufficiently large pores and should facilitate tissue growth/attachment. Results obtained in this study are compared to results of an earlier paper.


A combination of surface-sensitive techniques and electron transport measurements have been used to characterize the effect of argon ion bombardment and annealing on a series of InSb(100) samples. Ex situ electrical conductivity and magnetoresistance measurements at 4.2 K, and in situ high-resolution electron energy loss spectroscopy (HREELS) carried out at 300 K, indicate that all the samples studied exhibit enhanced n-type behaviour after the surface cleaning procedure. This effect is most pronounced after annealing to between 450 and 500 K and arises from the formation of a high-density electron gas with a sheet carrier concentration of approximately (6.5-9.0)*1012 cm-2. The carrier concentration is significantly reduced on annealing to higher temperatures up to a maximum of 700 K. Electron-energy-dependent HREELS measurements of the plasmon energy and intensity, in conjunction with model calculations based on dielectric theory, indicate that the n-type layer is approximately 500 AA thick and located approximately 175 AA below a surface depletion layer. The occupancy of the electronic subbands has been obtained by Shubnikov-de Haas measurements and self-consistent calculations. These show that the positive charge which confines the electrons is spread over approximately 300 AA with a best fit being provided by a Gaussian-like potential profile. The calculations demonstrate that the corresponding wavefunction spread for the i=0 subband, which contains approximately 40% of the total carriers induced, has a spatial dimension of approximately 500 AA in good agreement with the HREELS results.


This article investigates the endowment (waqf) foundation established by an Ottoman Sufi master of the Jilwatiyya order, ʿAzīz Maḥmūd Hudāʾī (1541–1628), and the impact of his philanthropic works on religious, social, and cultural life in sixteenth and seventeenth-century Istanbul. While providing his disciples with space for spiritual training in his Sufi lodge, Hudāʾī's waqf also funded public services at his mosque. In contrast to the perception of the Ottoman Empire as an "Oriental despotism," this article sheds light on the development of Hudāʾī's waqf foundation as part of a public sphere and foci of the vibrant civil society that emerged in Ottoman lands. Such investigation also aims to demonstrate how the philanthropic work of a single individual living in Ottoman Istanbul could provide a space for solidarity building and collective activities among local communities and spur their engagement in civic services and additional charitable donations.


A neuropsychological test battery designed to assess verbal learning and memory, visual memory, psychomotor speed, cognitive flexibility and concentration was administered to patients with panic disorder (N = 18) and social phobia (N = 18) and a group of healthy control subjects (N = 16). Overall, the neurocognitive performance of the panic disorder and social phobia patients was lower than that of control subjects. Analyses of the verbal test variables indicated reduced performance in panic disorder and social phobia patients, relative to control subjects, on measures of verbal learning and memory. In addition, panic disorder patients exhibited deficits on short-delay free recall. No group differences were observed on tests of visual memory, psychomotor speed, cognitive flexibility, and concentration. These results, while indicative of diminished neuropsychological test performance in patients with panic disorder and social phobia, do not suggest the presence of syndrome-specific or localized neurocognitive deficits.


The geometry of the multiple diffraction of a (001) silicon wafer in an x-ray powder diffractometer is elucidated. In particular, multiple diffraction occurs only when the sample is rotated (along the sample normal) to one of the specific azimuthal angles. A derivation based on analytical geometry is performed to obtain a general but closed formula for these azimuthal angles of multiple diffraction. Subsequent calculation shows that multiple diffraction occurs at 128 different angles in a full 360° scan to form a (002) `forbidden' reflection. Among these 128 multiple diffractions, 64 are double diffractions and the others are combined double and triple diffractions. The results of measurement obtained by a powder diffractometer show that only 96 of the 128 multiple diffractions are observed in the x-ray diffraction pattern due to the overlapping of some closely spaced diffraction peaks.


Breast cancer is a leading cause of morbidity and mortality among women. Much of the morbidity and mortality is associated with metastasis or local recurrence. There has been significant research on what can cause breast cancer progression and resistance to treatment. Carcinomas are made of transformed cells contained within stromal cells, fibroblasts, and immune cells. Difficulty in determining definite causal pathways of development of resistance and metastases is complicated by the heterogeneity of breast cancers. There are many different subtypes of breast cancer, each with certain unique phenotypes and genotypes. There has been shown 3 subsets of mammary cells: basal stem/progenitor cells, luminal progenitors, and non stem luminal cells. Although there is heterogeneity among the cell population of breast cancer tumors, there is generally a dominant cell type that allows classification of the tumor. There are at least four different breast cancer phenotypes. The first is the normal-like phenotype which resembles non cancerous breast cancer. The second is the luminal phenotype, generally ER positive and often divided into luminal A and luminal B categories. These breast cancers also express E-cadherein, KRT8, KRT18, and KRT19. The third category is HER-2 positive phenotype, which is generally ER negative. The fourth phenotype, designated as basal-like, generally overexpresses markers characteristic of normal mammary gland myoepithelium including EGF, p63, and basal cytokeratins KRT14, KRT17, and KRT5/6. However, a poorly differentiated phenotype has been established as a hallmark for aggressive breast cancers, which has suggested a role of stem cells in breast cancers. Stem cells are defined as cells that have the ability to undergo unlimited cell cycle divisions to create new stem cells that retain their undifferentiated state and multipotent differentiating potential. There are two broad categories of stem cells, embryonic and adult, or somatic, stem cells. Embryonic stem cells are found in the inner cell mass of blastocysts and involved in the differentiation of the embryo. Somatic stem cells are found in various tissues after embryogenesis with the main function of normal tissue repair and renewal. Examples include mammary stem cells found in breast tissue and recently associated with breast carcinomas, as well as mesenchymal stem cells, found in various locations throughout the body, including the bone marrow, and involved in modulating immune response. Many believe that the somatic stem cells are not as pluripotent as embryonic stem cells and should therefore be considered more as progenitor cells rather than stem cells. Progenitor cells are similar to stem cells in their ability for self-renewal and ability to differentiate into multiple


The slow rate of demixing is a major limitation in wide commercial exploitation of aqueous two-phase systems. In the present
work, use of a microwave field has been explored for the first time to enhance phase demixing rates (decrease demixing times) of
these systems. The microwave-field-assisted demixing process decreased the demixing time by about 2- to 4-fold in a polyethylene
glycol/potassium phosphate system and by about 1.5- to 6.5-fold in a polyethylene glycol/maltodextrin system. The enhanced demixing
rate can be explained by the dipole rotation, electrophoretic migration of free salts, multiple reflections at the interfaces,
droplet–droplet collision, and reduced viscosity of the continuous phase that occur during the application of a microwave field.


HD-6277 is a potent and selective G-protein-coupled receptor 40 agonist for the treatment of type 2 diabetes mellitus. Previous studies with HD-6277 showed enhanced glucose-stimulated insulin secretion and improved glycemic control in type 2 diabetic rodent models. To evaluate the potential benefits of HD-6277 on safety, tolerability, pharmacokinetics and pharmacodynamics, HD-6277 was investigated with six and four sequential cohorts in single and multiple ascending doses in healthy subjects as randomized, double-blind, placebo-controlled study, respectively. HD-6277 was well absorbed over all doses under fasting conditions and systemic exposure was increased in dose-dependent manner both in single and multiple ascending dose study. There was no severe or serious adverse events showing generally mild and transient profile, which suggested no safety concerns with the doses administered. Therefore, this study showed HD-6277 was safe and well tolerated in healthy subjects. Its exploratory efficacy on type 2 diabetes mellitus patients is currently under evaluation. Disclosure K. Kim: Employee; Self; Hyundai Pharmaceutical Co., Ltd. P. Kim: Employee; Self; Hyundai Pharmaceutical Co., Ltd. H. Yang: Employee; Self; Hyundai Pharmaceutical Co., Ltd. Funding Korean Ministry of Health and Welfare (HI17C2529)


This paper addresses the theoretical fallout from empirical studies published in the 1990s that showed no negative relationship between the introduction of minimum wages and employment. The theoretical developments have proved to be very meagre and this, it is alleged, is due to the unwieldy neo-classical framework which can only accommodate such an anomalous relationship in circumstances where employers face positive labour supply curves and for a small increase in wages. It fails to explain why more generalised minimum wages did not adversely affect unemployment. An earlier debate on the effects of minimum wages occurred in the 1940s and 1950s which provoked a dialogue between Neo-classical theorists and their Institutional critics as to the nature of economic research. Since then the framework of analysis has narrowed considerably, with only explanations consistent with the neo-classical view of optimisation by rational agents in a world of diminishing returns being theoretically acceptable. This has led to the impoverishment of economics and can partially explain the crisis in the profession when real world phenomena are at variance with the predictions of idealised models.


School leaders' tasks have become increasingly complex, as a result of globalization, a shift towards knowledge based economies, greater student diversity and an increased government focus on education policy reforms targeting and affecting schools. The role of school principals has moved from administrative leadership towards focusing on student outcomes, with more autonomy and accountability, and increased responsibilities for implementing policy reforms in schools and classrooms. This article focuses on how policies can ensure that school leaders contribute to school improvement. It builds on an international OECD study on school leadership which analyzed practices across 22 education systems in 2008 and explores developments since to propose policy options that can contribute to support the professionalization of school leadership. Among the key strategies suggested that many countries have been taken up are: clarifying the role of school leaders based on the tasks that make most difference on school outcomes; ensuring there is specialized training and development: that working conditions are attractive to ensure that there are quality professionals in exercise and that it is a sustainable profession that is well supported.


The implementation of conventional sparse principal component analysis (SPCA) on high-dimensional data sets has become a time consuming work. In this paper, a series of subspace projections are constructed efficiently by using Household QR factorization. With the aid of these subspace projections, a fast deflation method, called SPCA-SP, is developed for SPCA. This method keeps a good tradeoff between various criteria, including sparsity, orthogonality, explained variance, balance of sparsity, and computational cost. Comparative experiments on the benchmark data sets confirm the effectiveness of the proposed method.


Understanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to osteoarthritis. Here we identified a ubiquitin signature that is unique to injured articular cartilage tissue (the "injury ubiquitinome"). A total of 408 ubiquitinated peptides mapped to 114 proteins were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum(ER), also known as the ER-associated degradation(ERAD) response, including YOD1, BRCC3, ATXN3 and USP5 as well as the ER stress regulators, RAD23B, VCP/p97 and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB specific activity probes. Inhibition of DUBs using a broad-spectrum inhibitor caused a reduction in the injury-induced inflammatory response in a zebrafish tail fin injury model. These results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and osteoarthritis. This link through the ERAD pathway makes this protein set attractive for further investigation in in vivo models of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases.


Inelastic neutron scattering experiments and specific heat measurements have been performed on polycrystalline samples of PrFe2X2 (X=Si, Ge), a tetragonal intermetallic system showing a low-temperature antiferromagnetic ordering of the Pr sublattice, with no local magnetic moment on the iron site. The temperature variation of the specific heat, and the values of the magnetic entropy, indicate for both compounds a crystal-field energy level scheme characterized by two closely spaced singlets, split by about 1 meV for X=Ge and by about 2.5 meV for X=Si, with the other levels positioned above 7 meV. These conclusions are confirmed by the observation of only one excitation peak in the magnetic neutron scattering response in this energy range. In the paramagnetic phase, the inelastic peak is centred at 2.4(1) meV for X=Si and at 0.8(1) meV for X=Ge. Below TN, the peak position shifts to 2.8(1) meV for X=Si, and to 2.7(1) meV for X=Ge. The experimental findings are explained by a crystal- and molecular-field model with two low-lying singlets, coupled by exchange in the ordered phase. The different size of the molecular field in the two compounds, with respect to the crystal-field splitting of the low-lying singlets, causes the large difference in the ordered moments of the Pr3+ ions (1.41 mu B for Si and 2.75 mu B for Ge). The asymmetric shape of the peaks in the neutron scattering function has been attributed to the presence of two branches of magnetic excitons in these crystal-field systems showing manifestly Van Vleck-induced antiferromagnetism of singlet-singlet type.


Simulating time evolution of generic quantum many-body systems using classical numerical approaches has an exponentially growing cost either with evolution time or with the system size. In this work, we present a polynomially scaling hybrid quantum-classical algorithm for time evolving a one-dimensional uniform system in the thermodynamic limit. This algorithm uses a layered uniform sequential quantum circuit as a variational ansatz to represent infinite translation-invariant quantum states. We show numerically that this ansatz requires a number of parameters polynomial in the simulation time for a given accuracy. Furthermore, this favourable scaling of the ansatz is maintained during our variational evolution algorithm. All steps of the hybrid optimization are designed with near-term digital quantum computers in mind. After benchmarking the evolution algorithm on a classical computer, we demonstrate the measurement of observables of this uniform state using a finite number of qubits on a cloud-based quantum processing unit. With more efficient tensor contraction schemes, this algorithm may also offer improvements as a classical numerical algorithm.


Previous observational and modeling studies have indicated the importance of finescale winds in determining the circulation near Point Conception in the Santa Maria Basin (SMB) and the Santa Barbara Channel (SBC), California. There has not been a systematic attempt, however, to analyze and quantify the sensitivity of the near-surface circulation to different wind data. Here, a regional circulation model of the SMB and SBC is driven using three wind datasets: the European Centre for Medium-Range Weather Forecasts (ECMWF; 110 km 110 km horizontal grid), the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS; 9 km 9 km horizontal grid), and a blended wind product that combines Special Sensor Microwave Imager (SSM/I), ECMWF, and buoy and coastal wind data and that is referred to as SEB. A springtime period (March–May 1999) in which equatorward wind dominates and wind stress curls are strong is chosen for the study. Two groups of experiments are conducted: with and without assimilating moored temperature observations. The focus is on long time scales of greater than weeks and on mean currents. Comparisons between these experiments and between model and observation show that the circulation driven by the ECMWF wind is much weaker than that by the other two winds. On the other hand, the SEB dataset shows locally intensified wind stress curls behind capes and coastal bends, whereas these wind stress curls are weak in COAMPS. It is found that these small-scale variations in the wind field force alongshore inhomogeneous pressure gradients that in turn can significantly affect the near-coast currents. The result is that modeled currents forced by SEB agree better with observations than do those produced by COAMPS. Empirical orthogonal function analyses were conducted on the near-surface currents, sea level, wind, and wind stress curl. The mode-1 current (40%) is unidirectional (i.e., generally equatorward or poleward) and correlates well with the mode-1 wind (90%). The mode-2 current (20%) is cyclonic in the SBC and poleward inshore and equatorward offshore in the SMB; it correlates well with mode-1 sea level (70%), which suggests that mode-2 currents are driven by the pressure gradient. It is significant that neither mode-2 current nor mode-1 sea level correlates well with mode-1 wind stress curl (70%); rather, they correlate well with the time integral of the mode-1 wind stress curl. These conclusions support a previous theoretical idea that cyclonic circulation in the SBC and the inshore currents of the SMB are both driven by alongshore pressure setup induced by the time integral of the wind stress curl, rather than by the wind stress curl itself. This idea of a pressure setup is consistent with the differences found between the currents driven by COAMPS and SEB winds.


Comparison group selection is paramount for health policy evaluations, where randomization is seldom practicable. Rolling enrolment is common in these evaluations, introducing challenges for comparison group selection and inference. We propose a novel framework, GroupMatch, for comparison group selection under rolling enrolment, founded on the notion of time agnosticism: two subjects with similar outcome trajectories but different enrolment periods may be more prognostically similar and produce better inference if matched, than two subjects with the same enrolment period but different pre‐enrolment trajectories. We articulate the conceptual advantages of this framework and demonstrate its efficacy in a simulation study and in an application to a study of the effect of falls in Medicare Advantage patients.


OBJECTIVE
To evaluate prospectively whether generalized vulvar dysesthesia and vestibulodynia possess unique characteristics that support the theory of differing etiologies.

STUDY DESIGN
Women with vulvar dysesthesia for a minimum of 3 months were enrolled at the University of Michigan in 2 clinics specializing in vulvar disorders. Informed consent was obtained. Participants completed a 27-page questionnaire and had a physical examination. Differentiation of generalized vulvar dysesthesia and vestibulodynia was based on tenderness to light pressure isolated to the introitus vs. pain beyond the introitus, respectively. We compared women with the 2 diagnoses to each other on demographic characteristics, exposures, pain characteristics and physical findings using t test, Mann-Whitney U and chi 2 analysis.

RESULTS
Between January 26, 2001, and August 28, 2002, we enrolled 39 women, aged 18-60 years, with tenderness localized to the vestibule (vestibulodynia) and 17 with generalized vulvar dysesthesia. Women in each diagnostic group were similar in demographic and exposure characteristics. The pain characteristics were similar between the 2 groups except that recent pain was rated as worse by those with generalized vulvar dysesthesia. Activities that aggravated or relieved the pain were similar. However, women with generalized vulvar dysesthesia were more likely to state that their pain was aggravated by sitting and by washing the area. Similar results were found when using "continuous" pain rather than vulvar pain location as the outcome variable.

CONCLUSION
The characteristics of women with generalized vulvar dysesthesia are similar to those with localized pain, supporting the theory that the 2 disorders may exhibit 2 presentations on a continuum of severity seen in vulvar dysesthesia rather than 2 distinct entities.


The baluns used in broadband microwave mixers are often in the form of suspended microstrip circuits with tapered conductors. These structures have been analysed using TEM theory of the even and odd modes and results are presented for typical cross-sections. Tapers were approximated by cascading short lengths of uniform line and calculations and measurements were carried out on various tapers. The performance of the baluns is poor at frequencies where the even mode resonates. Between the resonances, the tapers perform better as a balun than a similar structure using uniform strips of equal width. The resonances can be damped by suitably loading the even mode.


Dr. Golem. How to Think About Medicine. By Harry Collins and Trevor Pinch. University of Chicago Press, Chicago, 2005. 258 pp. $25, £17.50. ISBN 9780226113661. Collins and Pinch present eight case studies (including tonsillectomies, chronic fatigue syndrome, and vaccination) to explore the uncertainties and limitations of medical science.


Secondary clarifiers form a crucial component in gravity separation processes mainly in solid-liquid separation. They perform the crucial process of separating the activated sludge from the clarified effluent and also to concentrate the settled sludge. As treatment plants receive increasingly high wastewater flow, conventional sedimentation tanks suffer from overloading problems which result in poor performance. Inlet baffle modification by using an energy dissipating inlet (EDI) was proposed to enhance the performance in the circular clarifiers in Al-Dewanyia wastewater treatment plant. A 3-Dimensional fully mass conservative clarifier model was applied to evaluate proposed tank modification and to estimate the maximum capacity of the existing and modified clarifiers. A Computational Fluid Dynamics (CFD) model was formulated to describe tank performance and design parameters were obtained based on the experimental results. The study revealed that velocity and SS are better parameters than TS, BOD5, and COD to evaluate the performance of sedimentation tanks. Removal efficiencies of suspended solids, biochemical oxygen demand, and chemical oxygen demand were higher in the EDI (Baffle).


In the present paper, we discuss the kinetic equations for the evolution of particles of a nanodispersed substance, distinguishing by properties (sizes, velocities, positions, etc.). The aim of the present investigation is to determine the coefficients for the equations by the distribution functions, which are obtained experimentally. The experiment is characterized by the time interval, which is needed for the measurement of the distribution function. However, the nanodispersed substance is obtained from a highly supersaturated solution or vapor and this time interval is large, thus, one is able to measure distribution functions only when the processes of the integration and the fragmentation of the particles become rather slow. So it is advisable to reconstruct the kinetics for the formation of a nanodispersed substance by the experimental distribution functions measured when the processes are rather slow. The first problem that arises is the obtaining of correct equations, and, hence, the derivation of the equations from each other. From the discrete system of equations for the evolution of discrete distribution functions of particles of a nanodispersed substance, we obtain the continuum equation of the Fokker-Planck type, or of the Einstein-Kolmogorov type, or of the diffuse approximation on the distribution function of nanoparticles distinguishing by the numbers of molecules forming them. We consider the distribution functions, which approximate the experimental data. We determine the coefficients for the equation of the Fokker-Planck type by the stationary and non-stationary distribution functions of a nanodispersed substance. Due to unity of the kinetic approach, the present work may be useful for specialists of various areas, who study the evolution of structures (not only with nanosize) with differing properties.


If the core purpose of transformative education is to challenge and reposition knowledge through a range of opportunities, then surfacing and attending to forms of student misconceptions (for example, through confusion, disequilibrium) are a necessary part of learning and teaching. We have come to understand that arriving at a clear view of a concept may involve a process of working through a range of misconceptions about a phenomenon or experience that may or may not create a threshold experience in a learner. We argue that the journey through conceptual change and thresholds requires a more nuanced emphasis on liminal spaces, where misconceptions and thresholds may reside. We offer a revised thresholds concept generic model that helps to identify student misconceptions as cycles within and through pre-liminal, liminal and post-liminal spaces. Two practice examples demonstrate the application of this model: (1) teaching and learning botanical literacy through a technology-rich, real-time mobile app and (2) embedding and measuring cultural competence as a graduate learning outcome in Australian universities. Each context offers a specific emphasis on highlighting the need to make all liminal learning spaces safer, as learners surface and engage with conceptual change. The conclusion suggests that conceptual change in student learning offers a form of threshold misconception.


The growth of metal oxide nanocrystals with a well-organized crystalline phase is of fundamental and technological interest because in this way it is possible to tune their size-dependent unique properties. In this communication, we demonstrate the selective growth of monoclinic and tetragonal ZrO(2) nanocrystals of <10 nm diameter driven by controlling the surface energy, with and without capping by N(CH(3))(4)(+). The nanocrystals were grown in aqueous solution at 150 degrees C. It was revealed, by transmission electron microscopy, X-ray diffraction, Raman spectroscopy, and optical absorption studies, that the nanocrystals capped by N(CH(3))(4)(+) have a less defective pure monoclinic phase, while those without capping have a pure tetragonal phase with highly disordered oxygen vacancies. The N(CH(3))(4)(+) capping on the surface oxygen site can reduce the surface energy low enough to stabilize the monoclinic phase. By contrast, the bare surface oxygen site has higher energy; thereby, the lower surface energy tetragonal phase is formed spontaneously. The present concept is a promising universal approach to control the crystal phases of technologically important oxide nanocrystals.


The aim of this study is to identify which different character features the feebleminded persons were ascribed in the journals of health. The journals of health are taken from the county council archive of Kronoberg, and consider people who are born 1930, 1940 and 1955. Furthermore, this study investigates which adjectives these feebleminded persons were associated with, as well as if there was a difference between them. In order to reach the aim of the study, this study uses two theories together with a discourse analysis. The first theory is Erving Goffman's ideas of stigma, whereas we use Michel Foucault's theory of power as our second theory. The theory is about the relationship between power and knowledge, and how it is used as a form of social control through community institutions. The motives of stigma were that the feebleminded were seen as threats to society and the rest of the population. Thanks to our discourse analysis, the result was that the doctors mostly used a negative vocabular when they described all the different feebleminded persons in their journals of health. Additionally, this study also presents that the discourse of today differ from the discourse of 1930, 1940 and 1955.


Tumor metastasis, the cause of more than 90% of cancer cell mortality, is a multistep process by which tumor cells disseminate from their primary site via local invasion and intravasation into blood or lymphatic vessels and reach secondary distant sites, where they survive and reinitiate tumor growth. Activation of a developmental program called the epithelial-to-mesenchymal transition (EMT) has been shown to be a very efficient strategy adopted by epithelial cancer cells to promote local invasion and dissemination at distant organs. Remarkably, the activation of EMT programs in epithelial cells correlates with the appearance of stemness. This finding suggests that the EMT process also drives the initial cancer cell colonization at distant sites. However, recent studies support the concept that its reverse program, a mesenchymal-to-epithelial transition, is required for efficient metastatic colonization and that EMT is not necessarily associated with stemness. This review analyzes the conflicting experimental evidence linking epithelial plasticity to stemness in the light of an "EMT gradient model," according to which the outcome of EMT program activation in epithelial cells would be bimodal: coupled to stemness during initial activation, but when forced to reach an advanced mesenchymal status, it would become incompatible with stem cell abilities.


Still Struggling for Equality: American Public Library Services with Minorities by Plummer Alston Jones, Jr. Westport, CT: Libraries Unlimited, 2004. 269pp. ISBN 1-59158- Social equity has been a perennial issue of interest to scholars in various disciplines. In library and information science, through particularly the provision of Multicultural Information Services (MIS), equal information access has to some degree always been a concern for the American public library enterprise. Libraries, especially in the public sector, have explored the standards of MIS in a multitude of formats. Some researchers examine the characteristics of individual ethnic groups, including their information seeking behavior within unique cultural and social contexts. Others focus on the planning, implementation, and evaluation of multicultural programs. Still others study the impact of information technology, especially the Internet, on existing and potential MIS and different information retrieval mechanisms geared towards multilingual collections. In general, most research has dwelled primarily on how to provide MIS. Seldom have scholars examined the social and political backdrop that has created the present state of MIS. In other words, factors that have contributed to the development of Multicultural Information Services today are rarely studied. Looking back in history, the concept of equality/equity (with regard to MIS) has never been a fixed idea, but a moving target defined by a multitude of social forces. Thus, ascertaining the fundamental sources of influence on the conceptualization and provision of MIS is crucial to the understanding and future of MIS. Plummer Alston Jones, Jr.'s Still Struggling for Equality is therefore a timely book, which explores how MIS and the library profession in general are shaped by policies, with special emphasis given to the role played by judicial legislation and immigration laws. Jones examines the origins and development of MIS from this most incisive, yet rarely explored, perspective. In the context of a detailed exploration of American legislative activities, he chronicles the development of information services to minorities in public libraries from 1876 to 2003 and he singles out seven eras (1876-1940s, 1950s, 1960s, 1970s, 1980s, 1990s, and the present) to further understand the evolution of public libraries and the provision of MIS. These seven eras individually explicate the entangled social milieu through which public libraries' strategies developed from initial Americanization to assimilation, then to multiculturalism, and finally to globalization. Meanwhile, Jones particularly emphasizes developments within the ALA and the funding role and oversight of government agencies at the federal level. With detailed historical facts, Still Struggling for Equality is an excellent introductory textbook for the history of public libraries and the provision of MIS.


Exciton diffusion is considered to be of prime importance for controlling the recombination zone in organic light emitting devices. This is particularly relevant for organic lasers based on single crystals, where undesirable exciton-exciton annihilation at high concentrations is inevitable. Here, exciton diffusion is studied in bifluorene single crystals specifically designed for organic laser applications, therefore featuring exceptionally low threshold of light amplification. The non-destructive light induced transient grating (LITG) technique capable of simultaneously evaluating the exciton lifetime and diffusion coefficient along different directions of the crystal was employed for this study. Highly anisotropic singlet exciton diffusion with the diffusion coefficient varying from <0.05 up to 0.96 cm2/s (in a perpendicular direction) and the corresponding diffusion lengths changing from <60 up to 300 nm, respectively, was revealed in ethylene-bridged bifluorene crystals. The LITG results on the directionality of exciton diffusion are anticipated to be essential for devising single crystal based organic lasers.Exciton diffusion is considered to be of prime importance for controlling the recombination zone in organic light emitting devices. This is particularly relevant for organic lasers based on single crystals, where undesirable exciton-exciton annihilation at high concentrations is inevitable. Here, exciton diffusion is studied in bifluorene single crystals specifically designed for organic laser applications, therefore featuring exceptionally low threshold of light amplification. The non-destructive light induced transient grating (LITG) technique capable of simultaneously evaluating the exciton lifetime and diffusion coefficient along different directions of the crystal was employed for this study. Highly anisotropic singlet exciton diffusion with the diffusion coefficient varying from <0.05 up to 0.96 cm2/s (in a perpendicular direction) and the corresponding diffusion lengths changing from <60 up to 300 nm, respectively, was revealed in ethylene-bridged bifluorene crystals. The LITG results on the direct...


Using a combined ray tracing and Fokker-Planck code, an investigation is made on the propagation and absorption of the launched power spectrum during lower hybrid (LH) current drive in tokamaks, in a situation where toroidally induced ray stochasticity is important. Stochastic effects are correctly taken into account by tracing a large number of rays. The influence of the balance between the wave damping and the stochastic divergence of nearby ray trajectories in governing the power spectrum dynamics and in establishing the characteristics of the LH power deposition patterns is illustrated. It is shown that, when strong wave damping prevails, the launched power spectrum behaves regularly: the LH power deposition is localized and the absorbed power spectrum is very similar in shape to the launched one, although some broadening and shifting in the parallel wave index generally occur. If the wave damping is weak and stochastic effects are important, the rays end by covering the entire plasma cross-section and the power spectrum dynamics follows a diffusive pattern: the LH power deposition turns out to be extended and the absorbed power spectrum is much broader than the launched one, as a result of strong spreading towards the high absolute values of the parallel wave index


This study tests the effect of capital structure on the profitability of the Iraqi firms that listed in Iraq stock exchange. The study used statistical methods such as multiple regression model represented by ordinary least squares (OLS) as a technique to investigate the claimed effect of capital structure on the profitability by applying the same on four firms from the Iraqi industrial sector for the period (2004-2013). The study findings suggest that capital structure positively influence, in a significant way, on the profitability of listed firms in Iraq. Furthermore, profitability, and assets (firm-size) have been found to be negatively influencing the capital structure of the listed firms. These findings generally concur with the predictions of the pecking order theory and the signalling effects of capital structure decisions of firms. The concerned companies must have to enhance their firm size that negatively correlated with ROE, its growth and continuity.


Cardiovascular diseases (CVDs) are the number one cause of death globally according to the World Health Organization. They account for approximately 30% of all global deaths and incur great medical costs. Chronic or congestive heart failure (CHF) remains the most prevalent diagnosis requiring hospitalization. Current treatments for heart failure patients aim to improve quality of life by treating signs and symptoms but patient outcomes remain poor. Discovery and development of new heart failure therapies is an active research area seeking to address this unmet medical need. In this chapter, we review (1) new drugs in the clinic for existing targets and (2) new targets that are currently being evaluated in the clinic. Topics include new mechanistic and clinical research of the renin–angiotensin–aldosterone pathway, inotropes and treatments for dyslipidemia. In addition, novel mechanisms for heart failure including drugs targeting mitochondrial function, inflammatory pathways as well as kinase inhibitors are discussed.


Background: The purpose of this study was to obtain data on the prevalence of specialist doctors and Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) residents in Indonesia who suffered from Coronavirus disease 2019 (COVID-19) after receiving the second dose of COVID-19 vaccination using the Sinovac vaccine (CoronaVac) and the length of time infected with COVID-19 after the second Sinovac vaccination. Methods: We performed a descriptive observational study, using a cross-sectional design. Data collection took place between August 2021 and October 2021. The respondents in this study included specialist doctors and ORL-HNS residents who worked in various hospitals in Indonesia who had received the second dose of the Sinovac vaccination. Data collection was performed by means of Self-reporting Online Survey Platform (Google Form). Results: This study included 1,530 respondents, and 54.2% of respondents were women. Respondents consisted of 68.6% ORL-HNS doctors and the rest were residents with an average age of 41.46 years old. The distance between the first and second doses of Sinovac was mostly under one month, which was 71.3% of the respondents. A total of 76.3% of respondents did not have co-morbid diseases. Based on this study, 16.9% of respondents suffered from COVID-19 after the second dose of Sinovac vaccination. The length of time suffering from COVID-19 after the second Sinovac vaccination was 3-6 months (9.7%). Conclusions: Based on this study, 16.9% of respondents suffered from COVID-19 after receiving the second Sinovac vaccination and 9.7% suffered from COVID-19 after 3-6 months of Sinovac vaccination.


Turbulent mixing in the ocean has important effects on climate and the transport of energy and nutrients. Internal lee waves, which are underwater standing waves that result from a current flowing over a barrier, have become recognized as an important source of mixing in the ocean. Previous studies with remote observations and numerical models have predicted the existence of breaking deep internal lee waves driven by the tide, but until now, none have been observed directly.


We report on the characterization of recently developed submillimetric He gas jets with peak density higher than 10(21) atoms/cm(3) from cylindrical and slightly conical nozzles of throat diameter of less than 400 μm. Helium gas at pressure 300-400 bar has been developed for this purpose to compensate the nozzle throat diameter reduction that affects the output mass flow rate. The fast-switching electro-valve enables to operate the jet safely for multi-stage vacuum pump assembly. Such gaseous thin targets are particularly suitable for laser-plasma interaction studies in the unexplored near-critical regime.


The use of high-speed imaging was pioneered by Drs. Moore and von Leden in the 1960's. Using today's high-speed digital imaging (HSDI) technology, we can evaluate pathological states of vocal fold (VF) vibration in patients with VF paresis and paralysis that could not be resolved by stroboscopy. Twelve patients with VF paresis (n=8) and paralysis (n=4) underwent evaluation with both stroboscopy and with HSDI. In patients with paralysis and paresis, HSDI shows many differences in vibratory abnormalities that could not be observed with stroboscopy. The vibratory differences between the two sides were greatest in paralysis. Distinctly different fundamental frequency (F0) between the two sides were only seen in the paralysis group while paresis showed phase lag and delay in onset of vibration between the sides. Subtle differences in vibration in patients with paresis could be differentiated by objective image analysis and objective waveform analysis of the HSDI using signal analysis of the digital kymogram derived VF vibrogram (VFV).


Myocardial and pulmonary ischemia during cardiopulmonary bypass is associated with cardiac and pulmonary dysfunction that may result in poor outcomes after cardiac surgery. Beating heart valve surgery, utilizing continuous coronary perfusion with warm oxygenated blood, together with continuous pulmonary artery perfusion and alveolar ventilation during cardiopulmonary bypass, represents an emerging and exciting novel strategy for myocardial and pulmonary protection. In this article, we present preliminary clinical results, as well as basic and clinical evidence, indications, contraindications and limitations of these new evolving techniques.


Early embryonic death was experimentally induced by amnion rupture in pregnant heifers. The subsequent morphological alterations in the placenta were studied with light and electron microscopy, histochemical tests and electron microscope microanalysis. The material from the treated heifers differed from that inuntreated cows in the following aspects: the fetal-maternal junction was firm; many endometrial epithelial cells were desquamated and the remaining epithelium showed vacuolization or depletion of organelles; the trophoblast remained at the preattachment stage in its marked phagocytic activity and accumulation of lipid and glycogen, and many of the organelles were degenerated; and the mesenchyme contained extracellular deposits of iron and calcium. It is believed that the changes observed were caused by interruption of the fetal circulation followed by an accumulation of metabolic products.


A close association of autoimmune diseases or autoimmune phenomena in myasthenia gravis is well known. A comprehensive immunological study of 22 patients with myasthenia gravis showed that changes in the immune system mainly involve the thymus-derived lymphocytes (T cells). Anti-thymus antibody was present in 90% of the patients, and it paralleled the frequency of thymic abnormality in myasthenia gravis. It is postulated that in myasthenia gravis the altered T cell functions caused by anti-thymus antibody result in the formation of an array of autoantibodies including the factor which blocks the neuromuscular transmission.


We report on experimental observations of homoclinic snaking in a vertical-cavity semiconductor optical amplifier. Our observations in a quasi-one-dimensional and two-dimensional configurations agree qualitatively well with what is expected from recent theoretical and numerical studies. In particular, we show the bifurcation sequence leading to a snaking bifurcation diagram linking single localized states to "localized patterns" or clusters of localized states and demonstrate a parameter region where cluster states are inhibited.


Subword segmentation algorithms have been a de facto choice when building neural machine translation systems. However, most of them need to learn a segmentation model based on some heuristics, which may produce sub-optimal segmentation. This can be problematic in some scenarios when the target language has rich morphological changes or there is not enough data for learning compact composition rules. Translating at fully character level has the potential to alleviate the issue, but empirical performances of character-based models has not been fully explored. In this paper, we present an in-depth comparison between character-based and subword-based NMT systems under three settings: translating to typologically diverse languages, training with low resource, and adapting to unseen domains. Experiment results show strong competitiveness of character-based models. Further analyses show that compared to subword-based models, character-based models are better at handling morphological phenomena, generating rare and unknown words, and more suitable for transferring to unseen domains.


Using data mining techniques, we have studied a subset (1400) of compounds from the large public National Cancer Institute (NCI) compounds data repository. We first carried out a functional class identity assignment for the 60 NCI cancer testing cell lines via hierarchical clustering of gene expression data. Comprised of nine clinical tissue types, the 60 cell lines were placed into six classes-melanoma, leukemia, renal, lung, and colorectal, and the sixth class was comprised of mixed tissue cell lines not found in any of the other five classes. We then carried out supervised machine learning, using the GI(50) values tested on a panel of 60 NCI cancer cell lines. For separate 3-class and 2-class problem clustering, we successfully carried out clear cell line class separation at high stringency, p < 0.01 (Bonferroni corrected t-statistic), using feature reduction clustering algorithms embedded in RadViz, an integrated high dimensional analytic and visualization tool. We started with the 1400 compound GI(50) values as input and selected only those compounds, or features, significant in carrying out the classification. With this approach, we identified two small sets of compounds that were most effective in carrying out complete class separation of the melanoma, non-melanoma classes and leukemia, non-leukemia classes. To validate these results, we showed that these two compound sets' GI(50) values were highly accurate classifiers using five standard analytical algorithms. One compound set was most effective against the melanoma class cell lines (14 compounds), and the other set was most effective against the leukemia class cell lines (30 compounds). The two compound classes were both significantly enriched in two different types of substituted p-quinones. The melanoma cell line class of 14 compounds was comprised of 11 compounds that were internal substituted p-quinones, and the leukemia cell line class of 30 compounds was comprised of 6 compounds that were external substituted p-quinones. Attempts to subclassify melanoma or leukemia cell lines based upon their clinical cancer subtype met with limited success. For example, using GI(50) values for the 30 compounds we identified as effective against all leukemia cell lines, we could subclassify acute lymphoblastic leukemia (ALL) origin cell lines from non-ALL leukemia origin cell lines without significant overlap from non-leukemia cell lines. Based upon clustering using GI(50) values for the 60 cancer cell lines laid out by the RadViz algorithm, these two compound subsets did not overlap with clusters containing any of the NCI's 92 compounds of known mechanism of action, a few of which are quinones. Given their structural patterns, the two p-quinone subtypes we identified would clearly be expected to possess different redox potentials/substrate specificities for enzymatic reduction in vivo. These two p-quinone subtypes represent valuable information that may be used in the elucidation of pharmacophores for the design of compounds to treat these two cancer tissue types in the clinic.


Background: Dysregulation of the cyclin D-CDK4/6-Rb axis occurs in a substantial proportion of ER-positive (ER+) breast cancers and has been linked with endocrine resistance. Adding the CDK4/6 inhibitor palbociclib to endocrine treatment has led to a substantial improvement of the outcome of patients with ER+ metastatic breast cancer. However, with the increasing clinical use, acquired resistance to palbociclib is merging as a new major clinical challenge. Methods: The ER+ cell lines T47D and MCF7 have been shown to be highly sensitive to treatment with palbociclib. Using long-term co-culture with increasing doses of Palbociclib, we generated MCF7 and T47D cell line clones with acquired resistance to Palbociclib. Three distinct resistant clones were selected for each cell line showing an IC50 shift from sensitive to resistant of approximately 300nM to 3uM for MCF7 and 400nM to 3.5uM for T47D, respectively. Resistant cell lines were characterized using RNA sequencing and mass spectrometry-based phosphoproteomics. Effects on selected target proteins (eg pAKT, pS6, pRB, RB or Cyclin D1) were confirmed using Western Blots. To modify resistance to palbociclib, a targeted in vitro drug-screen was performed using a range of inhibitors of the PI3K/AKT/mTOR and MEK pathways. Results: Western blot analysis of resistant cell lines demonstrated sustained down-regulation of Rb and phospho-Rb in response to palbociclib, which was reversible after discontinuation of palbociclib. Mass spectrometry identified >6,000 peptides across parental and resistant cells corresponding to 4,757 phospho-peptides and 5,337 phosphorylation sites. Pathway analysis suggested increased activity in the P3IK/AKT/mTOR pathway in resistant clones (including Akt1, p90S6K and mTOR), as well as changes in p53 and apoptotic regulation (e.g. phosphorylation of BAD). In addition, resistant clones showed multiple phosphorylation changes in the Rho/Rac pathway, suggesting changes in cytoskeletal organisation and a more invasive phenotype. Targeted drug screening showed a variable pattern across resistant clones with increased sensitivity to co-treatment of palbociclib with AKT inhibitors, PI3K alpha/delta inhibitors and/or MEK inhibitors in selected resistant clones, whereas pan-PI3K or PI3K beta/delta inhibitors showed limited efficacy in the selected clones. Conclusions: Phosphoproteomic analysis of palbociclib-resistant ER+ breast cancer cell lines demonstrated up-regulation of PI3K/AKT/mTOR and anti-apoptotic pathways. Resistant cell lines were sensitive to inhibition of PI3K/AKT/mTOR and/or MEK pathways with distinct patterns of activity across resistant clones suggesting that co-treatment of CDK4/6 inhibitors and PI3K/AKT and/or MEK inhibitors warrants further investigation as potential new therapeutic strategies in palbociclib resistance. Citation Format: Lenihan C, Bouchekioua-Bouzaghou K, Shia A, Wilkes E, Casado-Izquierdo1 P, Cutillas P, Schmid P. Characterization of resistance to the selective CDK4/6 inhibitor palbociclib in ER positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-06-02.


Background: Soft tissue defects about the elbow with concurrent ligamentous instability can be challenging to treat. Methods: We present a case report of a lateral elbow wound that resulted in lateral ulnar collateral ligament deficiency and posterolateral elbow instability. Results: We describe our technique of a modified brachioradialis rotational flap, in which the muscle is rotated to cover the soft tissue defect, while the vascularized brachioradialis tendon is used to simultaneously reconstruct the lateral ulnar collateral ligament. This procedure successfully restored posterolateral elbow stability at the time of wound coverage. Conclusion: Elbow soft tissue defects with associated ligamentous injuries can be treated using a modification of the brachioradialis rotational flap.


The COVID-19 outbreak has become a global pandemic. Spatial variation in the environmental, health, socioeconomic, and demographic risk factors of COVID-19 death rate is not well understood. Global models and local linear models were used to estimate the impact of risk factors of the COVID-19, but these do not account for the nonlinear relationships between the risk factors and the COVID-19 death rate at various geographical locations. We proposed a local nonlinear nonparametric regression model named geographically weighted random forest (GW-RF) to estimate the nonlinear relationship between COVID-19 death rate and 47 risk factors derived from US Environmental Protection Agency, National Center for Environmental Information, Centers for Disease Control and the US census. The COVID-19 data were employed to a global regression model random forest (RF) and a local model GW-RF. The adjusted R2 of the RF is 0.69. The adjusted R2 of the proposed GW-RF is 0.78. The result of GW-RF showed that the risk factors (i.e. going to work by walking, airborne benzene concentration, householder with a mortgage, unemployment, airborne PM2.5 concentration and percent of the black or African American) have a high correlation with the spatial distribution of the COVID-19 death rate and these key factors driven from the GW-RF were mapped, which could provide useful implications for controlling the spread of COVID-19 pandemic.


In this study, Fritillaria arsusiana (Liliaceae) is described and illustrated as a new species from Hatay province in southern Anatolia, Turkey. It is related to F. amana and F. hermonis by habitus features and broadly campanulate flowers, but differs mainly by its bulb shape and size, smaller leaf and flower features, and flower colour. It has also been morphologically compared with F. wendelboi, F. pinardii, and F. latakiensis. The detailed description, diagnostic characters, original photographs, geographical distribution, habitat and phenology, etymology, conservation status, and identification key of the new and the related species are presented in this study. IUCN conservation status of F. arsusiana is suggested as Critically Endangered (CR).


Serving one of the largest metropolitan areas in the United States, the George Bush Intercontinental Airport (IAH) in Houston, Texas, is one of the 10 airports with the longest average taxi-out and taxi-in times. This paper assesses the congestion at IAH by analyzing taxi times and flight data during different hours of the day. The capacity of IAH is investigated by examining the number of departing flights on the ground. IAH is operating close to capacity most of the time. Because increasing airport capacity can mitigate congestion, this report develops a surface operation model based on analyzed results to achieve this aim. A mixed-integer programming formulation is proposed to optimize total taxi times by finding optimal taxi routes and the related schedules. The model is applied to a sample from real data.


Congruent with the second wave of feminism and continuing into the 1990s, a group of feminist compositionists felt that argument should not have a major, if any, place in the feminist classroom and began to redefine, revision, and reposition argument. With a rhetorician's bias, this report looks at one articulation of why they turned away from argument—Sally Miller Gearhart's claim that "any intent to persuade is an act of violence"—, what they turned to, some critique surrounding their approaches and theories, and how a broader understanding of rhetoric and the role of agonism in rhetoric and education can add depth to the feminist approach.


At critically high temperatures, atrioventricular (AV) block causes ventricular bradycardia and collapse of cardiac output in fish. Here, the possible role of the AV canal in high temperature-induced heart failure was examined. To this end, optical mapping was used to measure action potential (AP) conduction in isolated AV junction preparations of the rainbow trout (Oncorhynchus mykiss) heart during acute warming/cooling in the presence of 4 or 8 mM external K+ concentration. The preparation included the AV canal and some atrial and ventricular tissue at its edges, and it was paced either from atrial or ventricular side at a frequency of 0.67 Hz (40 beats min-1) to trigger forward (anterograde) and backward (retrograde) conduction, respectively. The propagation of AP was fast in atrial and ventricular tissues, but much slower in the AV canal, causing an AV delay. Acute warming from 15 °C to 27 °C or cooling from 15 °C to 5 °C did not impair AP conduction in the AV canal, as both anterograde and retrograde excitations propagated regularly through the AV canal. In contrast, anterograde conduction through the AV canal did not trigger ventricular excitation at the boundary zone between the AV canal and the ventricle when extracellular K+ concentration was raised from 4 mM to 8 mM at 27 °C. Also, the retrograde conduction was blocked at the border between the AV canal and the atrium in high K+ at 27 °C. These findings suggest that the AV canal is resistant against high temperatures (and high K+), but the ventricular muscle cannot be excited by APs coming from the AV canal when temperature and external K+ concentration are simultaneously elevated. Therefore, bradycardia at high temperatures in fish may occur due to inability of AP of the AV canal to trigger ventricular AP at the junctional zone between the AV canal and the proximal part of the ventricle.


Objectives: Cancer of the exocrine pancreas is the fourth leading cause of cancer-related deaths in the United States. The efficacy of a novel bioavailable anticancer agent, dimethylamino-parthenolide (DMAPT), and the cyclooxygenase 2 inhibitor, celecoxib, was evaluated in a carcinogen-induced developmental model of pancreatic cancer. Methods: Syrian golden hamsters were injected with N-nitrosobis(2-oxopropyl)amine, once weekly for 6 weeks. Upon the first injection, hamsters were randomized as follows: placebo, low-/high-dose DMAPT (20 and 40 mg/kg per day), low-/high-dose celecoxib (10and 50 mg/kg per day), or combination DMAPT/celecoxib (low/low, high/high). Results: The 32-week trial showed that 40 mg/kg DMAPT alone significantly decreased the size of gross pancreatic cancers relative to placebo. No significant difference in gross tumor number was observed between the treatment groups and placebo with the exception of 50 mg/kg celecoxib with a higher tumor incidence; this group also exhibited lower lymphotactin levels suggestive of decreased immune surveillance. Tumor invasion into adjacent organs and metastasis were not observed in the DMAPT/celecoxib treatment groups. Drug targets including prostaglandin E2, prostaglandin E2 metabolite and activated nuclear factor &kgr;B were significantly decreased. Conclusions: Dimethylamino-parthenolide and celecoxib have the potential to be novel chemotherapeutic agents for pancreatic cancer; however, further optimization or the use of other modalities may be required for chemoprevention.


The layered performance modeling approach is refined and extended to cover the latest CCITT Blue Book specifications. Specific submodels for the higher-level functional blocks, such as the message transfer part (MTP) level 3, the signaling connection control part (SCCP), the ISDN user part (ISDN-UP), and the transaction capabilities application part (TCAP), are given in a generic way, explicitly. With these submodels, generic models for signaling points and signaling transfer points are constructed. The major functional parts of the layered protocol architecture of SS7 are modeled in a generic way by extended queuing network elements such as full duplex flow controlled links, priority processors, multiple-chain multiple-class traffic streams, or elements for segmenting and reassembling of messages. The analysis of the whole network starts from a global traffic flow analysis, which takes all the different signaling message types, their paths through the network, and the load into account. The overall performance measures, such as end-to-end transfer times, are found from all the component delays. The analytical results have been validated by simulation, revealing a high degree of accuracy.<<ETX>>


We use molecular dynamics computer simulations to investigate a critical temperature T_c for a dynamical glass transition as proposed by the mode-coupling theory (MCT) of dense liquids in a glass forming Ni_{0.8}Zr_{0.2}-system. The critical temperature T_c are analyzed from different quantities and checked the consistency of the estimated values, i.e. from (i) the non-vanishing nonergodicity parameters as asymptotic solutions of the MCT equations in the arrested state, (ii) the ${\bf{g}}_m$-parameters describing the approach of the melt towards the arrested state on the ergodic side, (iii) the diffusion coefficients in the melt. The resulting T_c values are found to agree within about 10%.


Drug therapies are often designed to reproduce the physiological uctuations in normal biological agents, including hormones. These regimens entail the need for a periodic, yet sustained administration, and thus require the generation of oscillatory variations in concentrations. We extend (in part, by the explicit use of time-delayed arguments) a system introduced recently along this design, in which the oscillations are generated by the delayed response of the permeability of a membrane at the boundary of a reaction chamber. We completely analyse the stability of the equilibrium, and present conditions under which Hopf bifurcations are present. We also provide further conditions for multiple mode instabilities to occur, by the occurence of double Hopf bifurcations.


The enantio-discrimination of beta-chiral primary ammonium ions is achieved by a rational approach that utilizes three-center (bifurcated) hydrogen bonding. The extraction experiments on various selected guests reveal that the bifurcated H-bonding plays a crucial role for the chiral discrimination. The X-ray data obtained for an inclusion complex substantiate such interactions. Using the bifurcated H-bonding, the chiral molecular recognition with our C(3)-symmetric tripodal oxazoline receptors is extended generally toward ammonium ions of alpha-, beta-, and alpha,beta-chiral amines. Simple molecular models, evoking the bifurcated H-bonding, explain the chiral discrimination modes.


This paper presents an obstacle detection system for visually impaired people. User can be alerted of closed obstacles in range while traveling in their environment. The system we propose detects the nearest obstacle via a stereoscopic sonar system and sends back vibro-tactile feedback to inform the user about its localization. The system aims at increasing the mobility of visually impaired people by offering new sensing abilities.


In spite of the importance of chemoreception and chemical signals in the social organization of lizards, there are only a few studies examining the chemical composition of secretions of lizards used for scent marking. The secretion of the femoral glands of male Iberian rock lizards (Lacerta monticola cyreni) contains 44 lipophilic compounds, including several steroids (mainly cholesterol), and n-C6 to n-C22 carboxylic acids, and minor components such as esters of carboxylic acids, alcohols, squalene, and one lactone. These compounds were identified on the basis of mass spectra, obtained by GC-MS. Most lipids were detected in all individuals, although relative proportions of each chemical show a high interindividual variability. This variability might be related to the characteristics or physical and health condition of males and might be the basis of female choice based on chemical cues observed in this lizard species.


In this commentary, I place the maturing field of rural health research and policy in the context of the rural health disparities documented in Health United States, 2001, Urban and Rural Health Chartbook. Because of recent advances in our understanding of the determinants of health, the field must branch out from its traditional focus on access to health care services toward initiatives that are based on models of population health. In addition to presenting distinct regional differences, the chartbook shows a pattern of risky health behaviors among rural populations that suggest a "rural culture" health determinant. This pattern suggests that there may be environmental and cultural factors unique to towns, regions, or United States Department of Agriculture (USDA) economic types that affect health behavior and health.


This study is a cross-sectional analysis of the differences between SLE outpatients seen in Rheumatology departments at University centres in England, Brazil and Sweden, using a standard protocol. The demographic characteristics, extent and activity of disease of 209 patients with SLE were studied; 112 patients were seen in England, 33 in Brazil and 64 in Sweden. The median age of disease onset of Brazilian and English patients was 25 years and of Swedish patients 31.5 years. Disease activity was measured by the BILAG index. In most systems Brazilian patients experienced more activity than English patients and English patients more activity than Swedish patients. Non-Caucasians experienced more active disease than Caucasians. No sex or occupational differences were observed in disease activity. English patients were the most likely to have experienced photosensitivity, oral ulcers and haematological disorders, Brazilian patients renal disorders and Swedish patients discoid rashes. Brazilian patients were the most likely to be prescribed only one drug for treatment of SLE and to be taking steroids and the highest dose of steroids, in contrast to the European patients who were often prescribed steroids and an antimalarial agent or azathioprine. The results of this cross-sectional assessment of disease activity using a standardized instrument indicate that there are real differences in the extent and degree of activity of SLE in different national groups. This reflects a combination of genetic, environmental and social influences on disease expression and has implications for treatment and monitoring of SLE patients.


Without assuming prior legal knowledge, books in the Directions series introduce and guide readers through key points of law and legal debate. Questions, diagrams, and exercises help readers to engage fully with each subject and check their understanding as they progress. This chapter discusses the three special forms of criminal liability: strict liability (including absolute liability), vicarious liability, and corporate liability. A strict liability offence is an offence which does not require proof of at least one mens rea element. An absolute liability offence does not require proof of any mens rea elements. Vicarious liability imposes liability on the defendant for the acts or omissions of another person. Corporate liability relates to the liability of a company for a criminal offence.


In the present study, the effect of lithium alone or in combination with the ACE inhibitor, captopril or the AT1 receptor antagonist, telmisartan, were investigated in two animal models of stroke: First, the stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe hypertension associated with the development of cerebral, renal and cardiac dysfunction. In these animals, the onset of stroke is accelerated by salt-loading.. Second, a model of focal cerebral ischemia with 90 min occlusion of the middle cerebral artery (MCAO) followed by reperfusion. In the first set of experiment, we demonstrate that renin-angiotensin system (RAS) inhibitors markedly prolong survival time in salt-loaded SHRSP, and majority of animals not longer die from stroke after treatment with RAS inhibitors. RAS inhibitors reduce the number of apoptotic/necrotic cells in the brain tissue after 5 weeks of treatment. Lithium does not improve the effect of sufficiently dosed RAS inhibitors. In the secondary set of experiment, chronic treatment with lithium decreases the infarct volume and improves the neurological outcome in the normotensive Wistar rats with transient MCAO. The neuroprotective effects of lithium are associated with a reduction of activated caspase-3 expression and inhibition of DNA fragmentation in the ischemic penumbra of the brain cortex. RAS inhibitors do not influence the neurological deficits and infarct volume in these animals. RAS inhibitors reduce apoptosis and the degree of microglial activation in the ischemic penumbra of the brain cortex. However, there are no synergistic effects between RAS inhibitors and lithium in the rats with focal cerebral ischemia.


The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation.