Background: Fibrocartilaginous embolic myelopathy is a syndrome of spinal cord infarction caused by fis emboli identical to the nucleus pulposus of intervertebral disk. The signals were acute and not progressive, asymmetric in 92% and neuroanatomic regions were affected C6-T2 (n = 2), L3-T3 (n = 5) and L4-S3 (n = 5). The diagnosis was based on history, fi ndings on physical and neurological examination and exclusion of differential diagnosis. The aim of this study was to report twelve dogs treated at Hospital Veterinario Universitario (HVU), Universidade Federal de Santa Maria (UFSM) with a presumptive diagnosis of fis embolism. Cases: Seven males and fi ve females dogs were referred to the Veterinary Teaching Hospital of the Federal University of Santa Maria: three rottweiler dogs, two labradors retrievers, one fi la brasileiro, one chow-chow, one boxer, one schnauzer, one German shepherd, one mixed breed and one greyhound, aged between one year and three months and eleven. In all cases, the owners reported during the anamnesis partial or complete loss of movement of member(s) involved(s) acutely with no history of trauma. For anatomical localization of the lesion was performed neurological examination. As complementary exams were requested blood count, serum biochemistry, urinalysis, and radiography of the spine. Contrast radiography (myelography) and cerebrospinal fl uid analysis were performed only in eight dogs. Front of the historical, clinical fi ndings, neurological and complementary exams the presumptive diagnosis was fi brocartilaginous embolism. The dogs were subjected to passive physical therapy and showed satisfactory clinical improvement in the fi rst month after onset of clinical signs. Discussion: The myelopathy fi brocartilaginous embolism is commonly reported in dogs of large and giant breed. In this study, 92% were of large breeds. The mean age of onset of clinical signs in this study was 4.5 years, and male dogs, the most affected, result similar to that found in other studies. Neurological signs vary depending on the location and severity of ischemic lesions of the spinal cord and asymmetric signals in 55% to 61% of the dogs. Of the twelve dogs of this study, signals were asymmetric and eleven of them were affected neuroanatomic regions C6-T2 (n = 2), L3-T3 (n = 5) L4-S3 (n = 5). In other studies, the most affected areas were T3-L3 and L4-S3. Intensive physical activity seems to be involved in about half the cases of embolism few hours. Except for two dogs of breed rottweiler and SRD in this study, all had a history of physical activity at the onset of clinical signs. There were no changes in blood count, serum biochemistry, urinalysis, and radiography of the spine in the twelve dogs. With the exception of four dogs, the other underwent contrast radiography (myelography) and cerebrospinal fl uid analysis and only in German Shepherd and Labrador was observed intramedullary compression standard to myelography and mild lymphocytic pleocytosis and increased protein in the CSF, respectively. Diagnosis of fis embolism cases in this study was based on history, fi ndings on physical and neurological examination, exclusion of differential diagnosis by laboratory tests and clinical evolution. In ten dogs of this study, was performed only physical therapy and nine of them were observed clinical signs of recovery between one and fi ve weeks. The study brings to clinical relevance, the importance of fis embolism in the differential diagnosis of dogs with a history of acute loss of limb movements, with or without asymmetry, non-progressive, no pain on palpation of the spine. This may be favorable prognosis in patients with signs of recovery during the fi rst month.


MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I–restricted CD8+ T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 310 helix that flips from an exposed "open" position in the PR transition state to a "closed" position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46–53 of murine H-2Ld MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.


We test the effect of stake size on ambiguity attitudes. Compared to a baseline condition,wefind subjects to bemore ambiguity seeking for small-probability gains and large-probability losses under high stakes. They are also more ambiguity averse for large-probability gains and small-probability losses. We trace these effects back to stake effects on decisions under risk (known probabilities) and uncertainty (unknown probabilities). For risk, we replicate previous findings. For uncertainty, we find an increase in probabilistic insensitivity under high stakes that is driven by increased uncertainty aversion for large-probability gains and for small-probability losses.


In this thesis, I study numerical and semi-analytical models of self-gravitating protostellar discs, with the aim of furthering our understanding of the role of disc-self gravity in planet formation. At the time of writing, the ALMA era of observational astronomy is upon us. Therefore, I place my research into this context with synthetic images of both numerical and semi-analytical models. I begin with an examination into the apparent lack of convergence, with increasing resolution, of the fragmentation boundary in Smoothed Particle Hydrodynamics (SPH) simulations of a protostellar disc. I run a suite of SPH with different numerical implementations, and find that even very similar implementations can fundamentally change the final answer. I analyse a suite of SPH simulations that fragment to form gravitationally bound objects, with the motivation of informing future population synthesis model development. I find that fragment-fragment and fragment-disc interaction dominates the orbital evolution of the system even at very early times, and any attempt to produce a population of objects from the gravitational instability process must include these interactions. Before a disc fragments, it will go through a self-gravitating phase. If the disc cools globally on a timescale such that it is balanced by heating due to gravitational stresses, the disc will be in a state of quasi-equilibrium. So long as the disc mass is sufficiently low, and spirals are sufficiently tightly wound, then angular momentum transport can be described by the local approximation, for which there is an analytical description. Using this analytical description, I develop an existing 1D model into 3D, and examine a wide range of parameter space for which disc self-gravity produces significant non-axisymmetry. Using radiative transfer calculations coupled with synthetic observations, I determine that there is a very narrow range of parameter space in which a disc will have sufficiently large gravitational stresses so as to produce detectable spirals, but the stresses not be so large as to cause the disc to fragment. By developing a simple analytical prescription for dust, I show that this region of parameter space can be broadened considerably. However, it requires grains that are large enough to become trapped by pressure maxima in the disc, so I conclude that if self-gravitating spiral arms are detected in the continuum, it is likely that at least some grain growth has taken place.


A brand is defined as a specific name, symbol or design or, more usually some combination of these, that is used to distinguish a particular seller's product. Today with a considerable change over time, there is an increase in modern and sophisticated branding of both tangibles and intangibles. Brands, particularly those that are high in brand equity (value of the brand) can be organizations most powerful assets. Survey method has been adopted to elicit the views of local and global brand car owners. The customers' preference towards local and global brands is studied by administering structured interview schedule with 200 customers in Puducherry city. In time when competition is getting passionate, it is imperative for the firm to seriously evaluate factors that are not only important in creating strong brand equity but also assist them in achieving customer satisfaction and loyalty. The results of the study shows that brand preference and brand loyalty play an important role in creating brand equity. These components of brand equity must be coherent in their actions so that consistent image of the firm is realized and valued by customers.


In this paper, a novel approach to Petri net modeling of programmable logic controller (PLC) programs is presented. The modeling approach is a simple extension of elementary net systems, and a graphical design tool that supports the use of this modeling approach is provided. A key characteristic of the model is that the binary sensory inputs and binary actuation outputs of the PLC are explicitly represented. This leads to the following two improvements: outputs are unambiguous, and interaction patterns are more clearly represented in the graphical form. The use of this modeling approach produces programs that are simple, lightweight, and portable. The approach is demonstrated by applying it to the development of a control module for a MonTech Positioning Station.


This study on gender factors in the production of African eggplant (Solanum gilo) was conducted in Abia State, Nigeria. Multi-stage random sampling technique was used to select 120 farmers (60 male and 60 female African eggplant farmers) on who structured questionnaire was administered in two of the three agricultural zones of the State. Data were presented and discussed using both descriptive and inferential statistical approaches in percentages, frequencies, tables and t-test analyses. The result showed that relatively more males (58.3%) than females (50%) had contact with and reported to extension agents by GSM calls/phone calls, more males (86.67%) than females (59%) had larger farmland, and received more production instructions on practices in form of advice from the extension agents. The study further revealed that extension agents procured and gave more production inputs (credit/grant, agrochemical and others) to male farmers than to the female farmers. Thus the mean output (10739.03tons/ha) of male African eggplant farmers appeared greater than that of the females (8300tons/ha) but there was no significant difference in output by the sexes. Availability of improved electricity supply and extension education was needful in the communities. It was recommended that extension agent's capacity building and land reform policies should be sensitive on gender lines in the study area.


A methodology for the rapid prototyping of process control systems which is based on an original extension to classical Petri nets is presented. The proposed nets, called PROT nets, provide a suitable framework to support the following activities: building an operational specification model; evaluation, simulation, and validation of the model; and automatic translation into program structures. PROT nets are shown to be translatable into Ada program structures concerning concurrent processes and their synchronizations. The authors illustrate this translation in detail using, as a working example, the problem of tool handling in a flexible manufacturing system.


Background Heart failure (HF) is a serious complication of acute myocardial infarction (AMI). We explored the excess mortality associated with HF as an early or late complication of AMI and describe changes over time in such excess mortality. Methods and Results All patients hospitalized with an incident AMI and without history of prior HF hospitalization were followed up to 1 year after AMI discharge for episodes of HF. New HF episodes were classified as in‐hospital HF if diagnosed during the AMI hospitalization or postdischarge HF if diagnosed within 1 year after discharge from the incident AMI. Logistic and Cox regression models were used to explore the excess mortality associated with HF categories. Changes over time in the excess mortality were assessed by testing the interaction between HF status and study year. In‐hospital HF increased in‐hospital mortality 1.79 times (odds ratio [OR], 1.79; 95% CI: 1.68–1.91). The excess mortality associated with HF increased by 4.3 times from 2001 to 2009 (P interaction<0.001) as a consequence of a greater decline of in‐hospital mortality among AMI patients without (9% per year) compared to those with in‐hospital HF (3% per year). Postdischarge HF increased all‐cause and CVD mortality 5.98 times (hazard ratio, 5.98; 95% CI: 5.39–6.64) and 7.93 times (subhazard ratio, 7.93; 95% CI: 6.84 –9.19), respectively. The relative excess 1‐year mortality associated with HF did not change significantly over time. Conclusions Development of HF—either as an early or late complication of AMI—has a negative impact on patients' survival. Changes in the excess mortality associated with HF are driven by modest improvements in survival among AMI patients with HF as compared to those without HF.


A feeding trial was conducted to evaluate the effects of moderate dietary concentrations of deoxynivalenol (DON) during a 21-day feeding experiment on the performance of broilers. Fifteen 1-day-old broiler chicks were randomly divided into two groups. The control group was fed non-contaminated diet. Another group of broilers was fed a diet naturally contaminated with 5 mg DON/kg diet. Deoxynivalenol had no effect (p > 0.05) on feed consumption, feed conversion, body-weight gain, live body weight or mortality. The absolute and relative weight of the organs (gizzard, pancreas, heart, spleen, colon and caecum) were not altered by the dietary inclusion of DON contaminated grain. However, both the absolute and relative weight of small intestine was decreased (p < 0.01) in DON fed broilers compared to the controls. No gross lesions were detected in any of the organs of birds fed contaminated wheat during the feeding trial. The microscopic examination revealed that, the height and the width of villi in duodenum decreased (p < 0.05) in birds fed DON contaminated wheat compared to controls. On the other hand the height and the width of jejunum villi were not affected (p > 0.05). This study indicates that feeding DON for 21 days to broiler chickens at a concentration of up to 5 mg/kg of diet influenced the weight of the small intestine as well as intestinal histology, especially the duodenum, as evidenced by shorter and thinner villi. In conclusion, diets with DON contamination below levels that induce negative impact on health and performance could affect small intestinal morphology in broilers.


A class of feedback control policies for steering a magnetic particle in a viscous fluid and actuated by a magnetic field is presented. The magnetic field which is generated by an array of electromagnets can be adequately shaped by controlling the voltages of the electromagnets. Control design relies on a dynamical model which exploits the low-pass character of the electromagnets, the opposing viscous drag on the magnetic particle, and the nonlinear (quadratic) nature of the dependence of the magnetic force on the electrical currents passing through the electromagnets. It is shown that under a set of practically achievable conditions, the nonlinearity of the model can be canceled by incorporating an inverse nonlinear map in the controller so that the closed-loop system operates like a linear system. A systematic framework for determining an optimal inverse map and investigating its properties is developed and two important cases of minimum control effort and maximum robustness are discussed. The ability to control the magnetic particle along arbitrary trajectories is verified both in simulations and in an experiment.


A generalized rotate-and-fire digital spiking neuron model that can be implemented by a simple asynchronous sequential logic circuit is proposed. The model can exhibit various nonlinear phenomena and responses to stimulation inputs. It is shown that the model can reproduce five types of inhibitory responses of Izhikevich's simplified ordinary differential equation neuron model. In addition, field programmable gate array experiments show that a learning algorithm enables the model to automatically reproduce nonlinear responses of a biological neuron and neuron models in the neuron simulator.


The aim of this study was to determine whether more than once freezing and thawing of serum affects different patterns of anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) as also to determine for how many days can serum samples be reliably refrigerated (2-8oC) for these tests. A total of 20 ANA (6 homogenous, 3 speckled, 3 centromere, 2 nucleolar, 2 cytoplasmic and 4 mixed) and 6 ANCA (3 PR-3 positive cANCA, 2 MPO positive pANCA, one MPO negative pANCA) positive serum samples were evaluated. The ANA and ANCA tests were studied with the indirect immunofluorescent (IIF) method using commercial kits. The effect of freezing and thawing was evaluated by comparing frozen serum samples with fresh samples during 5 freezing and thawing cycles. In addition, we analyzed the effect of storage time in the refrigerator. In none of the ANA positive serum samples, except for one mixed pattern, was negativity found in the HEp-2 and liver cells after the freezing and thawing cycles and the 21 day refrigerated period. In ANCA positive serum samples, positivity similar to initial findings continued in all samples during five cycles in freeze/thaw group and at the end of 21 days, in the refrigerated group. It may be concluded that ANA and ANCA can be reliably analyzed in serum samples with five freezing and thawing cycles and after refrigeration up to 21 days.


Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high‐volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90‐day mortality rate = 2%), which were compatible with reports from Western high‐volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy.


A health minister has called on women to sue their surgeons for clinical negligence if they have experienced complications from mesh treatment.

Speaking in an adjournment debate about medical devices, Jackie Doyle-Price said that she did not want to pre-empt what will come out of the Cumberlege review, which is due to report later this year.1 But she said, "It is becoming clear that mesh was deployed far too insensibly—far too many women were given this treatment, often at comparatively young ages, given that this was going to stay in their body for a long time."

She said that the conversations that had taken place between women who were having this treatment and their surgeons were "utterly inadequate."

Doyle-Price told the House of Commons, "I say to those women who have …


Differences in depression between Puerto Rican and non-Latina White mothers providing care to their adult child with mental retardation were examined. The focus of this study is on how family problems may mediate the effect of the adult's behavior problems on the mother's level of depressive symptoms and how this process differs across the two groups of mothers. As hypothesized, family problems was a stronger predictor of depressive symptoms for Puerto Rican mothers than for non-Latina White mothers. In addition, Puerto Rican mothers were in poorer physical health, which further accounted for differences in depression between the two groups.


Kaposi's sarcoma of the lung patients with the acquired immune deficiency syndrome is often indistinguishable by clinical and radiographic criteria from opportunistic pneumonia. Pulmonary Kaposi's sarcoma and pneumonia may frequently be present in the same patient. Previous observers have commented on the repeated failure to establish a diagnosis of Kaposi's sarcoma of the lung by fibreoptic bronchoscopy. Thirteen fibreoptic bronchoscopies were performed in a series of 11 patients with thoracic manifestations of AIDS and Kaposi's sarcoma was identified in transbronchial or bronchial biopsy specimens in four patients. This diagnostic yield is comparable to that obtained only by open lung biopsy procedures in previous reports. Fibreoptic bronchoscopy may contribute to the correct management of the patient and facilitate an accurate prognosis by differentiating between opportunistic pneumonia and pulmonary Kaposi's sarcoma.


p202 is a murine interferon (IFN)-inducible protein belonging to a cluster of IFN-inducible genes (the 200 family) located in a segment of chromosome 1. It is a nuclear DNA-binding protein that is able to modulate transcription by interacting with a heterogeneous set of transcription factors, including NF-kappaB, (p50/p65), AP-1, c-fos, c-jun, and RB-1. The p202 protein is believed to attenuate cell growth/proliferation, mainly through the activation of IFN-stimulated of gene factor 3 (ISGF3), which binds IFN-stimulated response elements (ISRE) located in the promoters of type I IFN genes. In this report, we show that the p202 gene can also be induced by platelet-derived growth factor (PDGF), a mitogen known to drive G(0)-arrested cells toward reentry into the cell cycle. PDGF transiently enhances the steady-state mRNA level of p202 and increases the p202 protein level independently from IFN signaling, by acting at the transcriptional level on its promoter. The kinetics of p202 induction by PDGF are faster and more transient than those of IFN. These data identify p202 as a member of the IFN-inducible gene family that can be directly regulated by mitogenic stimuli.


This essay provides an analysis of Elizabeth Singer Rowe's Friendship in Death (1728), proposing that her fictional letters from the dead offer a new, distinctively Whig vision of heaven. Dominant Anglican theology, following Saint Augustine, held that heaven, in its spiritual perfection, is unimaginable for those on earth. Rowe, an Independent whose circle included Isaac Watts, argues just the opposite. Drawing on Milton, Addison, and Watts, Rowe makes a case for a heaven that is a meaningful sequel to this life, describing a place that is fully available to human sense and imagination and where the souls of the dead continue to work toward personal perfection and enjoy the pleasures of a celestial society.


Objective: To review evidence for the treatment of neuroleptic malignant syndrome (NMS) and to discuss how to rechallenge patients with neuroleptics when continued pharmacotherapy for chronic psychological illness is required. Data Sources: A PubMed search was conducted through March 2016 using available medical subject heading (MeSH) terms and keywords that included neuroleptic malignant syndrome, treatment, dantrolene, and bromocriptine. A manual search of article reference sections followed. Study Selection and Data Extraction: Case reports and case series in English that discussed NMS and atypical NMS treatment as well as neuroleptic rechallenge were included for review. Data Synthesis: The reported incidence of NMS was 0.02% to 0.03%, with a mortality rate of 5.6%. Current literature on NMS is primarily retrospective and emphasizes diagnostic criteria, causative agents, and potential pharmacotherapy. Details regarding timing of administration, dose, and duration of pharmacotherapy are inconsistently reported. Reported dosing strategies and outcomes have been summarized. Instances of rechallenge were infrequently reported but demonstrate that recurrence may happen at any time after NMS resolution. Recommendations regarding safe rechallenge are provided. Conclusion: NMS is a rare adverse drug reaction, with a complex pathophysiology and presentation. Timely diagnosis and discontinuation of antipsychotic therapy is the first-line treatment, followed by supportive care and pharmacotherapy. Antipsychotic rechallenge is often required and should be attempted only after a drug-free period and with a different agent, slowly titrated with close monitoring.


An eight channels subband audio codec is implemented for signals with 44.1 KHz and 16 bits per sample using Matlab. To achieve perfect reconstruction, a two channels QMF filter bank with cutoff frequency ω=π/2 is designed, based on an equiriple filter of 99 order. Seven stages of this bank are used to split the input into eight signals with sample rates from 2.76 to 11 KHz, which are coded from 1 to 16 bits depending on the band energy. To evaluate performance for three tracks in terms of similarity of input and output signals, a Mean Opinion Score (MOS) experiment with fifteen subjects was performed. The Euclidean Distance between spectrums was also measured. Results showed a fair similitude for two tracks and excellent for one. Compression factors above 96% were achieved. Keywords: subband coding, mean opinion score MOS, QMF filter banks, audio compression


A new type of organic molecule, calix[4]arene, is applied in a second-harmonic-generating waveguide device for the first time. Linear optical properties of the calix[4]arene waveguiding film have been measured with the prism-coupling method. The molecules in the film are oriented by a corona-poling technique. With a Maker-fringe experiment, the induced d(33) and d(31) at lambda = 1064 nm are determined at 8.6 and 2.0 pm/V, respectively. The calix[4]arene thin film has been applied to a Cerenkov-type device that generates second- harmonic light radiating into the glass substrate. The highest efficiency obtained is 0.23% for a fundamental wavelength of 820 nm by the use of fundamental power densities of 100 MW/cm(2) in the waveguide and a device length of 6 mm. A coupled-mode theory has been developed that can properly explain the experimentally observed second-harmonic-generating efficiency and the angle of radiation into the substrate. Two methods for the enhancement of device efficiency are proposed, both based o?n theoretical calculations with the coupled-mode theory. An enhancement of 2 orders of magnitude is feasible. (C) 1995 Optical Society of America.


Video inpainting aims to fill the given spatiotemporal holes with realistic appearance but is still a challenging task even with prosperous deep learning approaches. Recent works introduce the promising Transformer architecture into deep video inpainting and achieve better performance. However, it still suffers from synthesizing blurry texture as well as huge computational cost. Towards this end, we propose a novel Decoupled Spatial-Temporal Transformer (DSTT) for improving video inpainting with exceptional efficiency. Our proposed DSTT disentangles the task of learning spatial-temporal attention into 2 sub-tasks: one is for attending temporal object movements on different frames at same spatial locations, which is achieved by temporally-decoupled Transformer block, and the other is for attending similar background textures on same frame of all spatial positions, which is achieved by spatially-decoupled Transformer block. The interweaving stack of such two blocks makes our proposed model attend background textures and moving objects more precisely, and thus the attended plausible and temporally-coherent appearance can be propagated to fill the holes. In addition, a hierarchical encoder is adopted before the stack of Transformer blocks, for learning robust and hierarchical features that maintain multi-level local spatial structure, resulting in the more representative token vectors. Seamless combination of these two novel designs forms a better spatial-temporal attention scheme and our proposed model achieves better performance than state-of-the-art video inpainting approaches with significant boosted efficiency.


We propose a data-driven 3D shape design method that can learn a generative model from a corpus of existing designs, and use this model to produce a wide range of new designs. The approach learns an encoding of the samples in the training corpus using an unsupervised variational autoencoder-decoder architecture, without the need for an explicit parametric representation of the original designs. To facilitate the generation of smooth final surfaces, we develop a 3D shape representation based on a distance transformation of the original 3D data, rather than using the commonly utilized binary voxel representation. Once established, the generator maps the latent space representations to the high-dimensional distance transformation fields, which are then automatically surfaced to produce 3D representations amenable to physics simulations or other objective function evaluation modules. We demonstrate our approach for the computational design of gliders that are optimized to attain prescribed performance scores. Our results show that when combined with genetic optimization, the proposed approach can generate a rich set of candidate concept designs that achieve prescribed functional goals, even when the original dataset has only a few or no solutions that achieve these goals.


Extraordinary acoustic transmission (EAT) is investigated numerically and experimentally using a square lattice array (SLA) of both-sides-open disk resonators (BSODRs) in a steel slab immersed in water. Each BSODR comprises a disk resonator sandwiched by two tubes and is formed by sticking three steel plates together, where each plate is perforated with a SLA of holes. The lattice constants of the three plates are the same, but the diameters of the holes in the middle plate are larger than those in the top and bottom plates. The BSODR resonance results in low-frequency EAT, and it is shown that the BSODR's resonant behavior can be predicted using a spring–mass model. The EAT frequency can be reduced significantly by adjusting the diameters of the disk resonator and the tubes without changing their thicknesses. Oblique-incidence transmission shows that the low-frequency EAT is insensitive to the angle of incidence, and vibration of the top and bottom steel plates produces strong Fano-like line shapes in the EAT. Additionally, diffraction of the incident wave causes the steel plates to vibrate, and this excites two minor transmission peaks that correspond to Wood's anomalies. As the disk resonator diameter increases, several eigenmodes that are dominated by the vibrations of the steel plates appear and lead to additional high-frequency EAT peaks; this behavior may suit applications that require robustness against variations in the ambient material properties. This structure provides increased flexibility for control of the EAT effect and can be applied in acoustic filters and sensors.Extraordinary acoustic transmission (EAT) is investigated numerically and experimentally using a square lattice array (SLA) of both-sides-open disk resonators (BSODRs) in a steel slab immersed in water. Each BSODR comprises a disk resonator sandwiched by two tubes and is formed by sticking three steel plates together, where each plate is perforated with a SLA of holes. The lattice constants of the three plates are the same, but the diameters of the holes in the middle plate are larger than those in the top and bottom plates. The BSODR resonance results in low-frequency EAT, and it is shown that the BSODR's resonant behavior can be predicted using a spring–mass model. The EAT frequency can be reduced significantly by adjusting the diameters of the disk resonator and the tubes without changing their thicknesses. Oblique-incidence transmission shows that the low-frequency EAT is insensitive to the angle of incidence, and vibration of the top and bottom steel plates produces strong Fano-like line shapes in th...


In the cyanobacterium Synechocystis sp. strain PCC 6803 (Synechocystis 6803) delta-aminolevulinic acid (ALA), the sole precursor for the synthesis of the porphyrin rings of heme and chlorophyll, is formed from glutamate activated by acylation to tRNA(Glu) (G. P. O'Neill, D. M. Peterson, A. Schön, M. W. Chen, and D. Söll, J. Bacteriol. 170:3810-3816, 1988; S. Rieble and S. I. Beale, J. Biol. Chem. 263:8864-8871, 1988). We report here that Synechocystis 6803 possesses a single tRNA(Glu) gene which was transcribed as monomeric precursor tRNA and matured into the two tRNA(Glu) species. They differed in the extent of modification of the first anticodon base, 5-methylaminomethyl-2-thiouridine (O'Neill et al., 1988). The two tRNA species had equivalent capacities to stimulate the tRNA-dependent formation of ALA in Synechocystis 6803 and to provide glutamate for protein biosynthesis in an Escherichia coli-derived translation system. These results are in support of a dual role of tRNA(Glu). The levels of tRNA(Glu) were examined by Northern (RNA) blot analysis of cellular RNA and by aminoacylation assays in cultures of Synechocystis 6803 in which the amount of chlorophyll synthesized was modulated over a 10-fold range by various illumination regimens or by the addition of inhibitors of chlorophyll and ALA biosynthesis. In these cultures, the level of tRNA(Glu) was always a constant fraction of the total tRNA population, suggesting that tRNA(Glu) and chlorophyll levels are regulated independently. In addition, the tRNA(Glu) was always fully aminoacylated in vivo.


Relict landforms provide a wealth of information on the evolution of the modern landscape and climate change in the past. To improve understanding of the origin and development of these landforms we need better spatial measurements across a variety of scales. This can be challenging using conventional surveying techniques due to difficulties in landform recognition on the ground (e.g. weak visual/topographic expression) and spatially variable areas of interest. Here we explore the appropriateness of existing remote sensing datasets (aerial LiDAR and aerial photography) and newly acquired unmanned aerial vehicle (UAV) imagery of a test site on the upland of Dartmoor in SW England (Leeden Tor) for the recognition and automated mapping of relict patterned ground composed of stripes and polygons. We find that the recognition of these landforms is greatly enhanced by automated mapping using spectral two-dimensional imagery. Image resolution is important, with the recognition of elements (boulders) of <1 m maximised from the highest resolution imagery (UAV red-green-blue (RGB)) and recognition of landforms (10–100 m scale) maximised on coarser resolution aerial imagery. Topographic metrics of these low relief (0.5 m) landforms are best extracted from structure-from-motion (SfM) processed UAV true-colour imagery, and in this context the airborne LiDAR data proved less effective. Integrating automated mapping using spectral attributes and SfM-derived digital surface models from UAV RGB imagery provides a powerful tool for rapid reconnaissance of field sites to facilitate the extraction of meaningful topographic and spatial metrics that can inform on the origin of relict landform features. Care should be given to match the scale of features under consideration to the appropriate scale of datasets available.


Since the early 20th century, madrasah with its independent characteristics is accepeted by people gradually, as one of the Islamic education which plays an important role in the development and improvement of education quality in Indonesia. However its existence which is managed by people as much as 96% made it difficult to get its right to be supervised based on the letter of dicision from the Ministry of Religion. The government's aid is very important for process of modernizing the school. The madrasah system was related to the school Islamic identity in facing the competition of education in global era. Keyword: Islamic education, madrasah, education quality.


Acquired ichthyosis and cutaneous metastases occurred in a 59-year-old black woman with adenocarcinoma of the breast. Acquired ichthyosis has been associated with "solid" tumors such as carcinomas of the lung, colon, and breast in only a few cases. Systemic diseases, medications, and malignancies associated with acquired ichthyosis are reviewed, and the need for a thorough clinical investigation of patients with acquired ichthyosis is stressed.


The research described in this thesis is part of the worldwide effort to realise nuclear fusion as a future energy source. Nuclear fusion, the merging of light atomic nuclei to form heavier ones, is an attractive option for large scale energy production. Fusion powers the sun and stars, and could on earth produce electricity from abundantly available fuels, without CO2 or other hazardous emissions. For the fusion reactions to occur, the fuel needs to be heated to 150 million degrees centigrade at several times atmospheric pressure. Under these conditions the atoms are fully ionised and form a plasma. In the most promising reactor concept, the tokamak, this hot plasma is contained inside a toroidal vessel by a strong magnetic field. Part of this magnetic field is generated by a current that runs in the plasma itself. In a working reactor, the energy generated by the fusion reactions helps to keep the plasma at the required temperature. Hence it is important to minimise the rate at which energy is lost from the plasma. This energy loss is mainly caused by chaotic plasma motions called turbulence. Perturbations of the density and temperature as well as of the electromagnetic fields play a role in plasma turbulence and show strong interactions. The strong magnetic field in a tokamak suppresses the dynamics directed along it, rendering tokamak turbulence more or less two dimensional. This type of turbulence is characterised by the formation of large structures from the merging of smaller ones, like for example the emergence of hurricanes from small disturbances in the atmosphere. In the tokamak the size of these structures is limited to intermediate scales, the so called mesoscales, by the shape of the magnetic field. Mesoscale structures may influence the transport, which in turn can modify the driving forces for the turbulence. Since the turbulence creates the mesoscale structures, a feedback loop is set up through which self-organisation can occur. This self-organisation is the object of study in this dissertation. The main questions addressed by this work are to what extend heat transport in the plasma is influenced by self-organisation, and whether self-organisation can explain certain observations in experiment that are not yet fully understood. Two coherent phenomena emerging from chaotic turbulent interactions are considered of prime importance: Current generated by the interaction of turbulent flows and turbulent magnetic fields, the dynamo current, and layered rotational flows emerging from small scale turbulent motions, the zonal flows. A model for tokamak turbulence is studied, the Cylindrical ElectroMagnetic 2 Fluid Turbulence (CEM2FT) model, which is arguably the simplest model to capture nonlinear interactions between turbulence, transport and plasma properties in a tokamak including the physics of dynamo currents and zonal flows. In order to compare the CEM2FT model with tokamak experiments, it is implemented in a numerical code, CUTIE. A simple one dimensional diffusive model for neutral particles was implemented in the CUTIE code to provide a better description of the particle source. However, the simulations show that in the small tokamaks this study is aimed at the situation is too complicated to be described by this simple model. The most important mesoscale structures emerging from CUTIE simulations are described and discussed. These are compared to actual observations in tokamaks. It is shown that the CEM2FT model not only describes generally observed phenomena such as magnetic islands and ballooning structures, but also reproduces specific self-organised structures such as off-axis sawteeth and flattened q-profiles. The dynamo current is shown to be of particular importance in the latter. The edge of a tokamak plasma can be cooled by injecting a hydrogen ice pellet. In such experiments, it is often found that the central temperature rises. In CUTIE simulations the pellet induces a zonal flow that decorrelates turbulent eddies and moves inward. This suppresses the turbulence over an area extending into the centre of the plasma. Although the magnitude and time scale of the effect do not correspond to the experiment, the suppression of turbulent heat loss could explain the rise of central plasma temperature. Another way of perturbing a steady-state plasma is by switching off the microwave heating of the plasma. In experiments, it is found that the central plasma retains its heat for some time after the switch-off, which is attributed to a reduction of turbulent heat loss. The simulations do indeed show such a reduction, but at a different position due to the fact that the magnetic configuration of the experiment could not be reproduced in detail. It is clear, however, that the suppression of the turbulence is caused by a zonal flow that is driven by enhanced magnetic fluctuations. In general it is concluded that self-organisation, in particular via the dynamo current and zonal flows, plays an important role in turbulent tokamak transport.


Objective. To investigate the association of the functional FCRL3 single-nucleotide polymorphism (SNP) −169T/C with disease phenotypes and susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese. Methods. FCRL3 SNP −169T/C was genotyped in 573 patients with SLE, 670 patients with RA, and 758 controls. Genotype distributions and allele frequencies were compared among the 3 groups as aggregates or as stratified by clinical characteristics, autoantibody profile, and sex within patient groups. Results. Overall, FCRL3 SNP −169T/C was not associated with susceptibility to either SLE or RA. However, −169CC genotype was significantly reduced in leukopenia-positive SLE patients as compared to the leukopenia-negative SLE patients (CC vs CT+TT, p = 6 × 10−4, OR 0.444, 95% CI 0.279–0.708) and controls (p = 6.1 × 10−3, OR 0.583, 95% CI 0.396–0.857). On the other hand, −169TT genotypes were significantly more numerous in RA patients with non-destructive disease as compared with patients with destructive disease (CC+CT vs TT: p = 0.007, OR 1.672, 95% CI 1.149–2.432). The −169T allele frequency was also significantly increased in non-destructive RA compared with patients with destructive disease (C vs T: p = 0.010, OR 1.423, 95% CI 1.089–1.859). FCRL3 SNP −169TT homozygous donors were significantly more numerous among female cyclic citrullinated peptide (CCP)-negative RA patients versus female CCP-positive RA patients (CC+CT vs TT: p = 0.019, OR 1.64, 95% CI 1.085–2.479). Conclusion. The functional FCRL3 SNP −169T/C appears to play important roles in the development of certain phenotypes such as SLE leukopenia and RA disease severity in Taiwanese patients with SLE and RA.


CONSPECTUS: Oxidative cross-coupling reactions between two nucleophiles are a powerful synthetic strategy to synthesize various kinds of functional molecules. Along with the development of transition-metal-catalyzed oxidative cross-coupling reactions, chemists are applying more and more first-row transition metal salts (Fe, Co, etc.) as catalysts. Since first-row transition metals often can go through multiple chemical valence changes, those oxidative cross-couplings can involve single electron transfer processes. In the meantime, chemists have developed diverse mechanistic hypotheses of these types of reactions. However, none of these hypotheses have led to conclusive reaction pathways until now. From studying both our own work and that of others in this field, we believe that radical oxidative cross-coupling reactions can be classified into four models based on the final bond formations. In this Account, we categorize and summarize these models. In model I, one of the starting nucleophiles initially loses one electron to generate its corresponding radical under oxidative conditions. Then, bond formations between this radical and another nucleophile create a new radical, [Nu(1)-Nu(2)](•), followed by a further radical oxidation step to generate the cross-coupling product. The radical oxidative alkenylation with olefin, radical oxidative arylative-annulation, and radical oxidative amidation are examples of this model. In model II, one of the starting nucleophiles loses its two electrons via two steps of single-electron-transfer to generate an electrophilic intermediate, followed by a direct bond formation with the other nucleophile. For example, the oxidative C-O coupling of benzylic sp(3) C-H bonds with carboxylic acids and oxidative C-N coupling of aldehydes with amides are members of this model group. For model III, both nucleophiles are oxidized to their corresponding radicals. Then, the radicals combine to form the final coupling product. The dioxygen-involved radical oxidative cross-couplings between sulfinic acids and olefins or alkynes belong to this bond formation model. Lastly, in model IV, one nucleophile loses two electrons to generate an electrophilic intermediate, while the other nucleophile loses one electron to generate a radical. Then, a bond forms between the cation and the radical to generate a cationic radical, followed by a one-electron reduction to afford the final coupling product. The oxidative coupling between arylboronic acids and simple ethers was classified in this model. At the current stage, there are only a few examples presented for models III and IV, but they represent two types of potentially important transformations. More and more examples of these two models will be developed in the future.


Abstract Energy plays only a minor role in orthodox theories of economic growth, because standard economic equilibrium conditions say that the output elasticity of a production factor, which measures the factor's productive power, is equal to the factor's share in total factor cost. Having commanded only a tiny cost share of about 5 percent so far, energy is often neglected altogether. On the other hand, energy conversion in the machines of the capital stock has been the basis of industrial growth. How can the physically obvious economic importance of energy be reconciled with the conditions for economic equilibrium, which result from the maximization of profit or overall welfare? We show that these equilibrium conditions no longer yield the equality of cost shares and output elasticities, if the optimization calculus takes technological constraints on the combinations of capital, labor, and energy into account. New econometric analyses of economic growth in Germany, Japan, and the USA yield output elasticities that are for energy much larger and for labor much smaller than their cost shares. Social consequences are discussed.


Introduction High resolution MRI has shown to be a promising technique to differentiate various pathologies that may be the cause of vascular stenosis and allow characterization of atherosclerotic plaque composition. Currently, there is no standard protocol for MR-imaging of intracranial atherosclerotic disease (ICAD), nor is there a gold standard phantom to compare MR-sequences. In addition, data generated by MRI is dependent on MR technique as well as scanner hardware. In this study, a small batch manufacturing technique is developed to create a plaque phantom that provides a platform for establishing a uniform imaging method for diagnosis of ICAD. Materials and methods A stenotic basilar artery model was first prepared by infusing polyvinyl alcohol hydrogel (PVA) into the ABS core-shell mold. The ABS core-shell mold was 3D printed using the fused deposit manufacturing technique. Several freeze-thaw cycles were applied to cure the PVA hydrogel. Three stenotic vessel models were prepared and subjected to VasoCT scanning. Comparisons of the VasoCT reconstructions were performed to demonstrate the reproducibility of the abovementioned manufacturing technique. Two synthetic plaque components were attached to each stenotic vessel segment, namely a fibrous cap and a lipid core. A fibrous cap was constructed using a mixture of gadolinium chloride, agarose, carrageenan, sodium azide, water, and sodium chloride (T1 = 2859ms, T2 = 340ms). The lipid core was mimicked using a milk, sodium azide, and carrageenan mixture (T1 = 1099ms, T2 = 91ms). Each plaque component was prepared in a silicone mold with known shape and dimension. The plaque phantom was scanned using a Siemens 3T Trio or a 3T Philips MR scanner at 3 different sites and the results were compared. Results The differences in radius between 3 stenotic vessels are presented in the Figure 1. Variations in signal intensity between the fibrous cap, lipid core and vessel wall were observed on the T2 images acquired from all 3 centers (figures not shown here). Conclusion A plaque phantom composed of a stenotic vessel wall, a fibrous cap and a lipid core was successfully constructed for diagnosis of ICAD. Disclosures J. Chueh: None. T. Turan: None. T. Brown: None. T. LeMatty: None. H. Mao: None. R. Swartz: None. E. Feldmann: None. J. Rappleye: None. K. van der Marel: None. M. Gounis: None.


Osteochondritis dissecans is a noninfectious process involving the articular cartilage and the subchondral bone of certain long bones of the extremities, which, by sequestration from the articular surface, usually produces a single foreign body or, more rarely, two, in the contiguous joint. This body is originally of an osseocartilaginous composition, but its structure subsequently undergoes alteration by the fluids in the joints. The mesial half of the articular surface of the internal femoral condyle is the site most frequently involved, but the heads of the radius, femur and humerus may also be the sites of the process. Osteochondritis dissecans occurs preeminently in youth, and most commonly in the tall, rapidly growing boy. OTHER TYPES OF BODIES OF THE JOINTS Free bodies within the joints are encountered in conditions other than osteochondritis dissecans. All such bodies are grouped under the common heading of corpora libera articulorum or "joint mice." 1. Free


Teacher education is a complex policy and practice landscape and teacher educator roles are changing. This thesis investigates variation in how teacher educators in England account for their practices within initial teacher education, in the context of secondary mathematics. It sets out a view of their experiences of teacher education in relation to different ways of accounting for relations between knowledge about teaching and learning mathematics and knowledge of mathematics. Outcomes are based on interviews with sixteen participants, including both school-based and university-based teacher educators. Teacher educator accounts comprised four, hierarchically inclusive descriptions of learning in teacher education: (1) understanding teaching and learning in mathematics (2) linking teaching and learning with the subject discipline of mathematics (3) integrating teaching and learning with the subject discipline of mathematics (4) reconceptualisation of teaching and learning with mathematics. Accounts of teacher education are structured as expanding opportunities for student teachers to engage critically with the process of reconceptualising mathematical knowledge into 'school maths' knowledge. The most developed accounts position teacher education as drawing on opportunities for student teachers to experience interplay between mathematics and school mathematics through advanced and multiple mathematics perspectives. This interplay is a site of learning in teacher education. Participants hold a range of teacher educator roles, including school-based and university-based roles. Teacher educators in school-led roles were less able to draw on this interplay in practice and so this thesis is a further and timely contribution to the research about university-based teacher educators. This thesis contributes a curriculum forms perspective that focuses on teacher educator positions on the role of the curriculum in developing new teachers.


Much confusion exists over the role of the clinical nurse specialist. In this article, the author uses the example of rheumatology to highlight what the role of the nurse specialist should be and the importance of proper education and qualification to prepare nurses for this function.


Abstract. There have been previous reports on an increased oxidative capacity in muscle tissue from the diseased legs of patients with intermittent claudication. The present study was designed to correlate metabolic and morphological data and to investigate whether the metabolic adaptive changes in muscle tissue of claudicating legs were also reflected in morphological variables such as capillary supply, fibre type distribution, and fibre area. The activity of cytochro‐me‐c‐oxidase in gastrocnemius muscle was determined and the insulin and glucose uptakes were measured across the leg in the basal state and 10 min following intravenous administration of 25 g glucose. The finding of a reduced relative number of Type II B fibres and a reduced ratio Type II B/II A fibre area, as well as an increased capillary supply to Type II A, indicated that the most extensive morphologic changes in muscle tissue of claudicating legs had occurred in Type II fibres. The increased number of capillaries in contact with Type IIA fibres in muscle tissue from claudicating legs, compared with muscle tissue from control legs, suggested that the most apparent metabolic changes occurred in this fibre type in the adaptation process of these patients. The more pronounced morphologic and metabolic changes in Type II fibres suggest that these fibres are more intensely activated than Type I fibres during physical activity in claudicating legs. The insulin uptake correlated positively with the number of capillaries per fibre, suggesting that the endothelial surface area is one of the determining factors for insulin uptake. The percentage of Type II B fibres reflected to a certain extent the metabolic adaptation in muscle tissue.


In a survey of methods for determining hemianopic visual field defects, a distinction is made between gross visual field screening and actual visual field examination with kinetic and automatic static perimetry. These methods may be arranged according to increasing the concentration required as well as to ability to cooperate, as follows: hand-movement stimulation of shifts of gaze, finger-counting with repetition by the patient, brightness and color comparison among the respective halves and quadrants of the visual field, then kinetic perimetry with the Goldmann perimeter, and, most exacting of all, automated perimetry. The advantages of kinetic perimetry in cases of incipient bitemporal visual field defects are discussed. For visual field examination with automated static perimeters, test programs are chosen which have their test-point pattern shifted with respect to the principal meridian. The diagnostic situations in which visual field testing may and must not be limited to 30 degrees are presented in tabular form. Guidelines and criteria for localizing lesions have been developed, i.e., the vertical and horizontal limits of the major axes which pass through the fixation point and the temporal crescent. Consideration of the course of the nerve fibers in the retina and of the fact that exact separation between superior and inferior may only be found temporal to the foveola with corresponding nasal defects enables horizontally limited visual field defects originating within the eye to be distinguished clearly from those originating in the visual cortex. Vertical limits due to semidecussation at the chiasma permit a differentiation between prechiasmic and postchiasmic lesions. In homonymous defects, consideration of further simple anatomic features of the visual pathway, namely the knee of Wilbrand and that portion of the optic radiation which extends anteriorly to the temporal lobes and which represents the inferior retinal halves with characteristic defects, also enables lesions in the visual pathway to be localized more accurately.


Music and rhyme are indeed inseparable constituents of the human language in general and can undoubtedly play a double role in enhancing the communicative skills of the users of each given language if its innate prosaic and metric features are manipulated properly. Relatedly, when it comes to the issue of Second Language Acquisition a teacher can rely to a great extent on the potential power of music and rhyme since these features can facilitate the learning process through their numerous merits. In addition, it can be claimed, that aspect of learning in SLA which might take the advantage of the musical and rhythmic features of a language to a great extent is vocabulary learning for children as new learners. To find the extent to which such a claim is valid, the present study is to focus on a sample of Iranian Pre-School Children's EFL program revolving around vocabulary learning based on a three week syllabus designed to include vocabulary material in form of bilingual (Farsi- English) content-based poems. At the end of the six week syllabus through some oral quizzes the level of their proficiency in absorbing the new vocabulary were measured by trying to evaluate their recall or the involuntary vocabulary rehearsal. Taking the outcomes into consideration, finally it was revealed that the children had shown a greater knowledge of the new vocabulary items they were exposed to through poetry than those ones taught by ordinary non-prosaic language.


Solving the kriging equations directly involves the inversion of an n×n covariance matrix C, which becomes numerically intractable when n is too large. Under these circumstances, straightforward kriging of massive datasets is not possible. A common practice is to solve the kriging problem approximately by local approaches that are based on considering only a relatively small number of points that lie close to the target point or block, so as to say in a moving neighborhood. By definition, a moving neighborhood moves with the target. A data point which was within the neighborhood may suddenly be dropped, with a weight jumping from a non-zero to a zero value, in absence of screen effect. The resulting discontinuities of the kriging map are largely undesirable, for instance in digital elevation model. In this work, we propose a method to avoid such discontinuities. It consists in adding a term to the kriging estimation equation that penalizes the weights associated with the most outer data points of the neighborhood. Practically, the penalization relies on a distance function whose value is 0 in most part of the neighborhood and which continuously tends to infinity when approaching its edge. Mechanically, the weights associated with the most outer data points tend to zero as their distance to the edge of the neighborhood gets close to zero. Therefore, the continuity of the resulting kriging map and of the kriging variance map is ensured. General properties of the method are given and illustrated with numerical examples.


Analysis by a HPLC-ESI-MS top-down proteomic platform of specimens of human preterm newborn whole saliva evidenced high relative amounts of cystatin B and its S-glutathionylated,S-cysteinylated, and S-S 2-mer (on Cys(3)) derivatives, decreasing as a function of postconceptional age (PCA). The percentage of S-unmodified cystatin B was higher than the S-modified isoforms in the early PCA period, differently from adults where cystatin B was detectable only as S-modified derivatives. The percentage of S-modified derivatives increased as a function of PCA, reaching at the normal term of delivery values similar to those determined in at-term newborns, babies, and adults. Moreover, in the early PCA period, high relative amounts of the 1-53 and 54-98 cystatin B fragments were detected, decreasing as a function of PCA and disappearing at the normal term of delivery. In agreement with intact cystatin B, fragment 1-53 was detectable as S-unmodified and S-modified derivatives, and their percentages changed accordingly with the percentages of intact proteins, suggesting that the fragmentation process could be subsequent to and independent from the S-modification of the protein. This study highlights specific enzymatic activity in the oral cavity of preterm newborns not present in at-term newborns and adults, which can be a clue to specialized pathways occurring during fetal oral development.


Human immunodeficiency virus type 1 (HIV-1) infection persists for life, requiring the regular administration of antiretroviral therapy (ART) to suppress viral replication. Poorly tolerated side effects and the continued emergence of drug resistance mutations to current pharmaceuticals prompts the development of new therapies against novel targets. The HIV-1 capsid plays a critical role in every post-entry early virus life cycle step and its impairment is highly detrimental to successful infection. Combined with a high degree of mutational fragility and a lack of host cell analogs to either the monomeric capsid protein (CA) or the assembled capsid, these characteristics make capsid a viable target for therapeutic intervention. In this dissertation, we examined the influence of capsid from different virus strains on early virus life cycle steps in different cell types. We characterized differences in the infectivity defect of the cell cycle dependent CA mutation N57A when incorporated into the closely related lab-adapted virus strains HIV-1(NL4-3) and HIV-1(LAI). We extended these lab-adapted strain studies to include clinical isolates and demonstrated that a single CA amino acid polymorphism in the transmitted/founder strain HIV-1(CH040) enhances capsid stability compared with HIV-1(LAI). Examination of an HIV-1 sequence database revealed strong conservation of CA sequence and the potential for broader applicability of our findings in lab-adapted strains. Capsid interacts with numerous host proteins that facilitate virus infectivity. We examined the effects of inhibiting capsid interaction with three of these proteins, cleavage and polyadenylation specificity factor 6 (CPSF6), cyclophilin A (CypA), and nucleoporin 153 (Nup153), on virus infectivity. We also explored the manner in which a mislocalized, truncated form of CPSF6 (CPSF6-358) restricts virus infectivity. The capsid must become dissociated, or uncoat, within the host cell for early virus life cycle steps to proceed and lead to successful infection. We designed and performed initial testing of a new, live cell capable capsid permeabilization assay that will permit further insight into the initial steps of uncoating. Together, these studies serve to advance our understanding of how capsid functions to promote infection and how capsid mutations and differences in virus strains and cell types can alter virus infectivity.


Outer ring tilted or offset axially, caused by improperly fixing relatively to the inner ring, will produce remarkable systematic errors in measured radial clearance of a bearing. Analyzing their effects in detail on the results of measured radial clearances, they are found to be the main sources affecting the measurement accuracy. Measures for removing them are proposed. Based on these, a novel type of instrument for measurement of radial clearances of ball bearings has been developed. It could avoid the two kinds of systematic errors. The measuring principle, structures and working procedures of the instrument are presented. Test results show that the test time is less than 15 seconds per a part and the indication stability is between ±1.0 µm.


Complete removal of metal catalyst particles from carbon nanofibers (CNFs) and other carbon nanostructures is extremely difficult, and the envisioned applications may be compromised by the left-over impurities. To circumvent these problems, one should use, wherever possible, such catalyst materials that are meant to remain in the structure and have some application-specific role, making any removal steps unnecessary. Thus, as a proof-of-concept, we present here a nanocarbon-based material platform for electrochemical hydrogen peroxide measurement utilizing a Pt catalyst layer to grow CNFs with intact Pt particles at the tips of the CNFs. Backed by careful scanning transmission electron microscopy analysis, we show that this material can be readily realized with the Pt catalyst layer thickness impacting the resulting structure and also present a growth model to explain the evolution of the different types of structures. In addition, we show by electrochemical analysis that the material exhibits characteristic features of Pt in cyclic voltammetry and it can detect very small amounts of hydrogen peroxide with very fast response times. Thus, the present sensor platform provides an interesting electrode material with potential for biomolecule detection and in fuel cells and batteries. In the wider range, we propose a new approach where the selection of catalytic particles used for carbon nanostructure growth is made so that (i) they do not need to be removed and (ii) they will have essential role in the final application.


BACKGROUND/OBJECTIVES The Seoul Metabolic Syndrome Management (SMESY) program is a 1-yr lifestyle modification program targeting metabolic syndrome (MetS) in Seoul residents. This study investigated the associations between adherence to dietary guidelines and MetS among the SMESY program participants. SUBJECTS/METHODS Data of 54,385 participants aged 20–64 yrs who completed the SMESY program in 2015, had information on adherence to dietary guidelines, and were not medicated for diabetes, hypertension, or dyslipidemia were analyzed. Participants underwent MetS screening and completed a lifestyle questionnaire including adherence to 10 dietary guidelines before and after participation. Participants were classified according to the number of MetS risk factors at baseline (MetS group, ≥ 3; risk group, 1–2; healthy group, none). Adherence to dietary guidelines was determined from the number of "yes" responses regarding the fulfillment of each guideline on ≥ 5 days/week. Multiple logistic regression was used to evaluate associations between newly diagnosed MetS and changes in adherence to dietary guidelines. RESULTS In the MetS group, MetS prevalence decreased after the SMESY program (men, −41.9%p; women, −48.7%p), and all risk factors were significantly improved (P < 0.0001). All groups exhibited improved adherence to all dietary guidelines after participation (P < 0.0001). In the MetS group with positively changed adherence scores, the MetS prevalence decreased by −44.1%p for men and −49.5%p for women, whereas the prevalence in those with negative changes decreased by −38.1%p for men and −48.6%p for women. In the risk group, those with positively changed adherence scores had significantly decreased odds ratios (ORs) for newly diagnosed MetS compared with those with negative changes (OR, 0.70; 95% confidence interval [CI], 0.61–0.80 for men; OR, 0.88; 95% CI, 0.79–0.99 for women). CONCLUSIONS The SMESY program may effectively reduce the risk of MetS among adults with risk factors by improving adherence to dietary guidelines.


This study aims to compare the effect of Twitter and Facebook in teaching mechanics of writing by 20 Arabic-speaking EFL learners in an attempt to determine which tool is more effective. We adopt the experimental design of a pre- and post-test to measure the participants' knowledge of English mechanics of writing before and after the treatment, which involved taking part in describing a picture on these two social media networks for two weeks. We divided the 20 participants into two groups: one used Twitter and the other used Facebook to complete the description task. We administered a 100-word essay task as the pre- and post-test to determine whether the use of Twitter helped the participants improve their knowledge of the mechanics of writing more than the use of Facebook or vice versa. The results reveal that the difference between the numbers of errors produced by both groups were not statistically significant even though, the group that used Facebook produced a lower number of errors on the post-test. The subsequent semi-structured focus group discussions provided more insight into the answers of both groups on the post-test. The study concludes with recommendations for further research.


Universal Lax pairs of the root type with spectral parameter and independent coupling constants for twisted non-simply laced Calogero-Moser models are constructed. Together with the Lax pairs for the simply laced models and untwisted non-simply laced models presented in two previous papers, this completes the derivation of universal Lax pairs for all of the Calogero-Moser models based on root systems. As for the twisted models based on Bn, Cn and BCn root systems, a new type of potential term with independent coupling constants can be added without destroying integrability. They are called extended twisted models. All of the Lax pairs for the twisted models presented here are new, except for the one for the F4 model based on the short roots. The Lax pairs for the twisted G2 model have some novel features. Derivation of various functions, twisted and untwisted, appearing in the Lax pairs for elliptic potentials with the spectral parameter is provided. The origin of the spectral parameter is also naturally explained. The Lax pairs with spectral parameter, twisted and untwisted, for the hyperbolic, the trigonometric and the rational potential models are obtained as degenerate limits of those for the elliptic potential models.


Importance Electroconvulsive therapy (ECT) is a highly effective treatment for depression but is infrequently used owing to stigma, uncertainty about indications, adverse effects, and perceived high cost. Objective To assess the cost-effectiveness of ECT compared with pharmacotherapy/psychotherapy for treatment-resistant major depressive disorder in the United States. Design, Setting, and Participants A decision analytic model integrating data on clinical efficacy, costs, and quality-of-life effects of ECT compared with pharmacotherapy/psychotherapy was used to simulate depression treatment during a 4-year horizon from a US health care sector perspective. Model input data were drawn from multiple meta-analyses, randomized trials, and observational studies of patients with depression. Where possible, data sources were restricted to US-based studies of nonpsychotic major depression. Data were analyzed between June 2017 and January 2018. Interventions Six alternative strategies for incorporating ECT into depression treatment (after failure of 0-5 lines of pharmacotherapy/psychotherapy) compared with no ECT. Main Outcomes and Measures Remission, response, and nonresponse of depression; quality-adjusted life-years; costs in 2013 US dollars; and incremental cost-effectiveness ratios. Strategies with incremental cost-effectiveness ratios of $100 000 per quality-adjusted life-year or less were designated cost-effective. Results Based on the Sequenced Treatment Alternatives to Relieve Depression trial, we simulated a population with a mean (SD) age of 40.7 (13.2) years, and 62.2% women. Over 4 years, ECT was projected to reduce time with uncontrolled depression from 50% of life-years to 33% to 37% of life-years, with greater improvements when ECT is offered earlier. Mean health care costs were increased by $7300 to $12 000, with greater incremental costs when ECT was offered earlier. In the base case, third-line ECT was cost-effective, with an ICER of $54 000 per quality-adjusted life-year. Third-line ECT remained cost-effective in a range of univariate, scenario, and probabilistic sensitivity analyses. Incorporating all input data uncertainty, we estimate a 74% to 78% likelihood that at least 1 of the ECT strategies is cost-effective and a 56% to 58% likelihood that third-line ECT is the optimal strategy. Conclusions and Relevance For US patients with treatment-resistant depression, ECT may be an effective and cost-effective treatment option. Although many factors influence the decision to proceed with ECT, these data suggest that, from a health-economic standpoint, ECT should be considered after failure of 2 or more lines of pharmacotherapy/psychotherapy.


A first-time chemometric study of energy-dispersive X-ray (EDX) data of Charophyta gyrogonites is presented. Specimen provenance is a microbialitic carbonate lacustrine succession from the Triassic (Anisian, 243.8 ± 1.9 Ma) of the Cerro Puntudo Formation, San Juan, Argentina. Gyrogonites from three different strata of the succession are studied. Data obtained by EDX include major and minor components, which are analyzed by principal component analysis (PCA). The aim of this study is twofold: first to determine the preservation features of gyrogonites by way of a chemometric approach (i.e., EDX followed by PCA) and then to infer the likely, original chemical composition of the paleolake inhabited by charophytes. EDX spectra show the presence of O, Ca, and minor elements (e.g., Si and Mg), indicating a predominantly calcium carbonate (CaCO3) composition. Principal component analysis supports differences obtained between central and peripheral areas of the gyrogonites, indicating a higher CaCO3 content in their central part. On the other hand, in their outer part, the CaCO3 diminishes and the presence of Si compounds is recorded. No significant differences among gyrogonites from the three different strata are found, implying a similar preservation mode. This suggests a differential diagenetic pattern for the external cells of the gyrogonites than their centers. These results have implications regarding the chemical composition of the paleolake water (Si and Ca availability) and the provenance and catchment areas. Results are encouraging regarding the usefulness of a chemometric approach for studies of fossil remains in lacustrine environments when other techniques of chemical analysis are not available.


The theory of viscoelasticity in textile assemblies reported in Part I of this series of papers is extended to blended textile materials. The complex effects of ageing or an nealing or both of these on the stress relaxation processes in a blended textile material are separated into several regions according to the demarcation provided by the glass transition temperature of the constituent fibers in the blend. The influence of ageing or annealing processes on the mechanical properties contributed by constituent fibers in the blend can be represented by horizontally shifting the stress relaxation curves of the fibers in the logarithmic time scale. The time shift factors for each individual group of fibers in the blend take into account the changes in temperature and ageing or annealing history. The sufficient condition to obtain a single effective time shift factor for the blend is that all viscoelastic component fibers must have only one identical time shift factor with respect to the same reference state. The theory predicts that, in most real situations, there should be no single time shift factor obtainable for textile blends owing to the differences between the shift factor of the component fibers. The interaction between the fiber components in a blended fabric represents an important aspect of its viscoelastic behavior. An experimental study reveals that the interaction between fiber blend components in wool/polyester fabrics is influenced by the differ ences in the stress relaxation behavior of the blend constituents, blend composition, and fabric weave construction. The study also indicates that the annealing process improves the viscoelastic properties of wool/polyester blended fabrics. Optimum an nealing conditions occur when these fabrics are heated in the vicinity of the glass transition temperaure of wool fibers at the equilibrium moisture regain corresponding to 20°C and 65% RH.


Energy drinks are non-alcoholic beverage intended to enhance the psycho-physiological responses in human, which is especially popular among young generation in Nepal. It is normally high caffeinated drink added with other ingredients such as carbohydrates, amino acids, B-group of vitamins etc. In this study, 10 brands of energy drink available in Nepalese markets were taken then analyzed for quantitative determination of Caffeine and Taurine by HPLC-UV method. From the result obtained, pH and TSS values of energy drinks were found in the range of 2.96-3.81 and 6.64-18.21 respectively. Likewise, the Caffeine and Taurine content in same samples were found in the range of not detected (ND) to 35.78 mg/100 ml and ND to 387.5 mg/100 ml respectively. Only the 6 samples out of 10 were confi rmed caffeine content as per claimed in label, while only 3 samples were confi rmed for Taurine content as per label claimed. Based on this pilot study, the majority of samples did not meet the label claims in term of Caffeine and Taurine, which apparently indicated the misbranding of such drinks. Since, there is no any regulation for such energy drinks in Nepal, it seems to be a great challenge for regulation of their safety and misbranding.


The paper presents an application of artificial neural networks to the reliable detection of misfires in automotive engines. By government regulations, automobiles an required to be equipped with instrumentation to detect engine misfires and to alert the driver whenever the misfire rate has the potential to affect the health of emission control systems. A relevant model for the powertrain dynamics is developed as well as an explanation of the instrumentation. The basis for using a neural network to detect these misfires is explained and experimental system performance data (including error rates) an given. It is shown that the present method has the potential to meet the government mandated requirements.


Abstract. Periodic signatures present in the magnetospheres of both Jupiter and Saturn have yet to be fully explained. At Jupiter the unexplained signatures are related to emissions from the Io torus ("System IV"); at Saturn they are observed in emissions of kilometric radiation (SKR) and in magnetometer data. These signatures are often interpreted in terms of magnetic field anomalies. This paper describes an alternative mechanism by which the neutral atmosphere may impose such periodic signatures on the magnetosphere. The mechanism invokes a persistent zonal asymmetry in the neutral wind field that rotates with the planet. This asymmetry must be coupled to substantial ionospheric conductivity. It is then able to drive divergent currents in the upper atmosphere that close in and perturb the magnetosphere. We estimate the conductivities and wind speeds required for these perturbations to be significant, and argue that they are most likely to be important at auroral latitudes where the conductivity may be enhanced by particle precipitation.


Objectives To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) treated in hospital emergency departments (EDs) in Spain, and to assess associations between characteristics and outcomes. Material and methods Prospective, multicenter, nested-cohort study. Sixty-one EDs included a random sample of all patients diagnosed with COVID-19 between March 1 and April 30, 2020. Demographic and baseline health information, including concomitant conditions; clinical characteristics related to the ED visit and complementary test results; and treatments were recorded throughout the episode in the ED. We calculated crude and adjusted odds ratios for risk of in-hospital death and a composite outcome consisting of the following events: intensive care unit admission, orotracheal intubation or mechanical ventilation, or in-hospital death. The logistic regression models were constructed with 3 groups of independent variables: the demographic and baseline health characteristics, clinical characteristics and complementary test results related to the ED episode, and treatments. Results The mean (SD) age of patients was 62 (18) years. Most had high- or low-grade fever, dry cough, dyspnea, and diarrhea. The most common concomitant conditions were cardiovascular diseases, followed by respiratory diseases and cancer. Baseline patient characteristics that showed a direct and independent association with worse outcome (death and the composite outcome) were age and obesity. Clinical variables directly associated with worse outcomes were impaired consciousness and pulmonary crackles; headache was inversely associated with worse outcomes. Complementary test findings that were directly associated with outcomes were bilateral lung infiltrates, lymphopenia, a high platelet count, a D-dimer concentration over 500 mg/dL, and a lactate-dehydrogenase concentration over 250 IU/L in blood. Conclusion This profile of the clinical characteristics and comorbidity of patients with COVID-19 treated in EDs helps us predict outcomes and identify cases at risk of exacerbation. The information can facilitate preventive measures and improve outcomes.


High attrition in attempts to discover new pharmacological agents for the treatment of psychiatric disorders has triggered a decline in R&D investment in important disease categories such as schizophrenia and mood disorders. Poor knowledge about disease molecular pathology and molecular target validation coupled with notable costly failures involving clinical trials with highly novel and selective single target agents (STAs) have contributed to the development of this trend. One positive development arising from the current situation is the renewed interest in investigating approaches involving multi-target agents (MTAs), which have historically shown a strong track record of success and utility in the treatment of psychiatric disorders. However, it is clear that the traditional serendipity-dependent drug discovery approach for multi-target agents is suboptimal and has to evolve towards a new model of rationally designed and tailored MTAs. It is of course highly challenging to optimise compounds across several therapeutic targets whilst minimising potential broad receptor promiscuity as well as other properties to generate high quality drug candidates. Nevertheless, recent developments in medicinal chemistry approaches and pharmacological evaluation suggest that feasibility for tailored MTAs is not unrealistic. Appropriately designed MTAs, such as hybrids of validated and unprecedented novel molecular targets, offer a multi-functional pharmacology with the potential for multi-symptomatic efficacy and multi-indicational use. If successful this will help to address the compelling unmet medical need and the treatment requirements of schizophrenia and mood disorder patients as well as easing the burden of carers and the societal costs arising from these devastating illnesses.


The sources of right, which regulate relations in the field of solving of lands disputes, are analysed, the particularities of the formation and development of the legal securing of solving of the boundary lands disputes are exposed.


The present report is a comparison of the experimentally defined temperature and heat output of cooling fins in the air stream with theory. The agreement is close on the basis of a mean coefficient of heat transfer with respect to the total surface. A relationship is established between the mean coefficient of heat transfer, the dimensions of the fin arrangement, and the air velocity.


With the water tourism developed, making the development of water landscape rising rapidly. How to ensure the safety of hydraulic engineering technology under normal circumstances, and protect the ecological environment, play tourism economic benefits are an important problem in landscape design. Under the premise of following the principle of water conservancy landscape planning and design, applying AHP to research Xiya ditch waterfall landscape and optimize design program, then set up the preferred plan from ecological effect, waterfalls and technological factors three aspects of evaluation index. This provides theory basis for model test and engineering implementation in Xiya ditch waterfall landscape. In recent years, water conservancy projects relying on water industry form a large number of humanities landscape, natural landscape. The development of water tourism, gradually achieved a certain economic, social and environmental benefits. Giving full play to the comprehensive benefits of water conservancy projects, Ministry of Water Resources has granted water tourism as three major elements in water economy with water supply, power generation.


Background. 4-Aminopyridine (4-AP) is a Food and Drug Administration–approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. Objective. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. Methods. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. Results. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Conclusion. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.


Through a series of creative projects this doctorate set out to research how computer-assisted composition (CAC) of music affects decision-making in my compositional practice. By reporting on the creative research journey, this doctorate is a contribution towards a better understanding of the implications of CAC by offering new insights into the composing process. It is also a contribution to the composition discipline as new techniques were devised, together with new applications of existing techniques.

Using OpenMusic as the sole programming environment, the manual/machine interface was explored through different balances between manual and algorithmic composition and through aesthetic reflection guiding the composing process. This helped clarify the purpose, adequacy and nature of each method as decisions were constantly being taken towards completing the artistic projects. The most suitable use of algorithms was as an environment for developing, testing, refining and assessing compositional techniques and the music materials they generate: a kind of musical laboratory. As far as a technique can be described by a set of rules, algorithms can help formulate and refine it. Also capable of incorporating indeterminism, they can act as powerful devices in discovering unforeseen musical implications and results.

Algorithms alone were found to be insufficient to simulate human creative thought because aspects such as (but not limited to) imagination, judgement and personal bias could only, and hypothetically, be properly simulated by the most sophisticated forms of artificial intelligence. Furthermore, important aspects of composition such as instrumentation, articulation and orchestration were not subjected to algorithmic treatment because, not being sufficiently integrated in OpenMusic currently, they would involve a great deal of knowledge to be specified and adapted to computer language. These shortcomings of algorithms, therefore, implied varying degrees of manual interventions to be carried out on raw materials coming out of their evaluations. A combination of manual and algorithmic composition was frequently employed so as to properly handle musical aspects such as cadence, discourse, monotony, mechanicalness, surprise, and layering, among others. The following commentary illustrates this varying dialogue between automation and intervention, placing it in the wider context of other explorations at automating aspects of musical composition.


A case study in South Ecuador serves as an example to understand the dynamics
of adoption of agroforestry species. Agroforestry species become
important in land that is totally devoid of forest cover. They can reduce
soil degradation, increase local biodiversity and at the same time increase
household income. Their use can be seen as a new practice that spreads
throughout a region by means of social networks. Sharing information
about this potentially sustainable agricultural innovation has become important
in a region like southern Ecuador. In this region there are mainly
two ethnic groups, namely the Saraguro and the Mestizo-colonos. In the
first group are indigenous people and the latter are migrants from other
places of the country that went to settle the region during the agrarian
reform. The two ethnic groups do have different traditions and land use
practices.
Qualitative research shows that there are potential differences in adoption
of agroforestry tree species between two ethnic groups. The low adoption
rate of Saraguro communal leaders may be an indicator of lower contagion
than Mestizo-colonos. Contagion refers to actor i adopting the same
innovation as actor j with whom actor i had contacted. It is proposed
a heterogeneous diffusion model that addresses network exposure effects
and a generalized blockmodel for relational data analysis. It was first hypothesized
that the Saraguro indigenous group may have lower access to
the information necessary for the adoption of the innovation than Mestizo-
Colonos. Nonetheless, the results show that Mestizo-colonos have higher
adoption rate than Saraguros.
The network actors' behaviour is shaped by local characteristics, for instance
their ethnicity. For the analysis it was taken into account the search
for advice for the main agricultural activities for the household. On this
base, it is proved that indeed there are structural differences on search for
advice between ethnic groups. By analyzing ethnic subgroups, the subgroup
of Mestizo-colonos has the actors with highest degree of centrality
and betweenness. These actors are in the highest cohesive block in cohesive
block analysis. Furthermore, a high Burt's constraint shows that low
access to structural holes in the network create a differentiation of information
sharing between groups. Higher Burt's constraint indicates less access
to the information located in other clusters in the network. The periphery
of the network plays an important role as a source of advice, as shown
by cohesive bloc analysis, which we complement with a k-core analysis.
The k-core analysis suggests that different and more diverse information is
accessed by Mestizo-colonos as compared to Saraguros. In applied terms
this suggests that Saraguros tend to share more similar information within
their group than do Mestizo-colonos.
In order to understand patterns of network structure the Exponential Random
Graph Models (ERGM) become important. For example, ERGMs
help to valuate the importance of reciprocity in the network relations depending
on how many reciprocal dyads are found in the observed network.
Fitting an exponential random graph model (ERGM) to the network, it is
shown that indeed there are differences between two ethnic groups in the
way they share information. We explore the network patterns in the sharing
on agroforestry species. Sharing information with similar others is
limited to the less commercial tree species. The most commercial tree
species information is concentrated in one actor, who is Mestizo-colono.
Transitive network effects are identified within ethnic groups as long as
they share information on different tree species (others than pine). The
two ethnic groups share information of different tree species. This shows
a different knowledge, where Mestizo-colonos are more related with commercial
species.


This thesis proposes the Home Care Routing Problem with Time Windows (HCRPTW) which is an extension to the well-known Vehicle Routing Problem with Time Windows (VRPTW). Different than VRPTW, we solve the routing problem of the health care personnel of a Home Health Care (HHC) service provider when the patients require different types of services. In this problem, the patients may request different types of care which can be provided by two types of personnel: nurses and health care aides. Each patient must be visited exactly once even if her servicing requires both personnel and is associated with a strict time window during which the service must be provided. In order to solve this problem, we present the 0-1 mixed integer programming formulation of the problem. The problem can be modeled with three different objective functions which are to minimize the total distance travelled, to minimize the total number of personnel and to minimize the total number of vehicles. We randomly generate a set of instances based on Solomon's benchmark problems for the VRPTW and solve them using IBM ILOG CPLEX. We also study Crew Constrained Home Care Routing Problem with Time Windows (CC-HCRPTW) which is another extension of HCRPTW where the number of each type of personnel is limited.


The impact of the intestine in determining the oral bioavailability of drugs has been extensively studied. Its large surface area, metabolic content and positioning at the first site of exposure for orally ingested xenobiotics means its contribution can be significant for certain drugs. However, prediction of the exact metabolic component of the intestine is limited, in part due to limitations in validation of in vitro tools as well as in vitro-in vivo extrapolation scaling factors. Microsomes are a well established in vitro tool for extrapolating hepatic metabolism, however standardised methodologies for preparation in the intestine are limited, in light of complexities in preparation (e.g. presence of multiple non-metabolic cells, proteases and mucus). Therefore, the aims of this study were to establish an optimised method of intestinal microsome preparation via elution in the proximal rat intestine, and to determine microsomal scaling factors by correcting for protein losses during preparation. In addition, to assess species in another preclinical species (dog) and human as well as assessing and regional differences in scaling factors and metabolism. Following optimisation of a reproducible intestinal microsome preparation method in the rat, the importance of heparin in limiting mucosal contamination was established. These microsomes were characterised for total cytochrome P450 (CYP) content, and CYP and uridine 5?-diphosphate glucuronosyltransferase (UGT) activities using maker probes of testosterone and 4-nitrophenol. Loss corrected microsomal scaling factors between two pools of n=9 rats was 9.6�3.5 (recovery 33%). A broad range of compounds (n=25) in terms of metabolic activity and physicochemical properties were screened in rat intestinal microsomes. The prediction accuracy relative to in house generated or literature in vivo estimates of the fraction escaping intestinal metabolism (FG) through in vitro-in vivo extrapolation of observed metabolism and the derived scaling factors and either Caco-2 permeability of physicochemical permeability estimates utilising the Qgut model. In the dog, regional differences in intestinal scaling factors and metabolic activities were explored, as well as relationships between the proximal intestine and liver in matched donors. Positive correlations in both hepatic activity and microsomal scalars were observed. Robust scaling factors were established using the 3 microsomal markers. A total of 24 compounds were screened for hepatic and intestinal metabolism in order to make in vivo estimates of FG, the fraction escaping hepatic metabolism (FH) and oral bioavailability (F). Estimates based on Caco-2 and physicochemical based scaling, as well as utilising a commercial PBPK software platform (ADAM model, Simcyp� v12) were broadly similar with generally reduced prediction accuracy in proximal physicochemical based Qgut scaling, and improved predictions using Caco-2 Qgut or PBPK approaches. Worse predictions were observed for compounds with high protein binding, transporter substrates and/or CYP3A inhibitors. Regional metabolism demonstrated peak metabolism in the proximal intestine, before declining distally. Human intestinal microsomes were prepared for jejunum and ileum tissue. Although samples were limited, regional differences in metabolic activities and scaling factors were also assessed, using correction markers and activity in 23 compounds. In all, 20 compounds overlapped between all three species. Comparison in Fa.FG between rat and human CYP3A substrates showed a modest relationship, however relationships between species and human were generally poor given the observed differing metabolic contributions of testosterone and 4-NP metabolite formation between species limited the observed relationships between species. However, within species, good estimates of oral bioavailability were observed. This is the largest know interspecies comparison of intestinal metabolism and scaling factors with microsomes prepared within the same lab.