The UNMIX model was used to analyze the source of heavy metals found to be present in the topsoil of parks in the main district of Lanzhou City. The Hakanson toxicity response coefficient was used concurrently to modify the traditional weights in the model, and the matter-element extension model was used to evaluate heavy metal pollution. The results of the evaluation were compared with the comprehensive pollution index (PN) and potential ecological risk index (RI). The results were as follows. ①The average heavy metal content in the topsoil at each sampling point was higher than that of the background value of soil in Lanzhou, with the proportion of Ni, Cu, and Co being 100% while the proportion of Cr, V, Pb, and As contents were 58.82%, 14.71%, 20.59%, and 2.94%, respectively. ② The results of source analysis showed that there were three major sources of heavy metal pollution in the topsoil of the parks in the study area. Source 1 is construction pollution, which contributes 56% of the Co present. Source 2 is traffic pollution, which contributes 44% and 52% of Cu and Pb, respectively. Source 3 is natural, and contributes 62%, 60%, 56%, and 56% of V, Cr, Ni, and As, respectively. Thus, this research showed that natural sources are predominant. ③ The weight correction effect for each heavy metal was significant; there was an approximately 44% reduction in both Cr and V, while the corrected weights of Ni, Cu, Pb, As, and Co increased in the order Co < Pb < Cu < Ni < As compared with the conventional weights. The most obvious change in weight was that of As, which increased by approximately 188%. ④ The results of the evaluation using the matter-element model showed that the state of 46% of the topsoil in the parks in the study area was grade Ⅴ (severely polluted), while 41% was grade Ⅳ (moderately polluted) and 3% was grade Ⅲ (lightly polluted); Co was the main pollutant. The results of the model evaluation were roughly the same as of from the PN and RI, indicating that the matter-element extension model can be used to evaluate heavy metal pollution in soil and the evaluation results are accurate and objective.


Summary.  A prerequisite for the success of intracytoplasmic sperm injection (ICSI) is the use of viable sperm that will support oocyte activation and embryo development. Usually, spermatozoa are selected according to motility, which is a clear indication for viability. However, in cases with complete asthenozoospermia, it is impossible to select viable sperm by morphological means. Here we report for the first time on the use of a laser to discriminate between viable and dead immotile spermatozoa. The application of a single laser shot to the far end of the sperm tail causes a curling of the sperm tail only in viable sperm, similar to the reaction observed in the hypo‐osmotic swelling test. Using this method for sperm selection prior to ICSI we achieved high fertilization and cleavage rates in cases with immotile sperm in fresh testicular biopsy material as well in cases with ejaculated immotile sperm. It is concluded that laser sperm interaction allows for the identification of viable but immotile spermatozoa.


The European Union welcomed the demonstrators' demands wholeheartedly during the Arab Spring, trying to maximize the assistance that it could offer to support genuine democratic transition, at least at a rhetorical level. This article reflects on the changes in the neighborhood policy by focusing on public perceptions measured in Europe and in countries in close proximity to the Israeli–Palestinian conflict. European views on solidarity are compared to local public opinion on EU involvement in the region. Recipient views in Jordan, Egypt, Palestine, and Israel are explored by analyzing relevant results of the Arab Barometer and Neighborhood Barometer surveys. Findings indicate that the Middle Eastern public opinion tends to appreciate the EU's gestures with the exception of Egypt, but conditionality is more in line with European public opinion.


Abstract Introduction: Disulfiram-ethanol reaction (DER) due to acetaldehyde accumulation occurs after drinking ethanol during disulfiram therapy. DER may result in life-threatening toxicity requiring urgent critical care. Fomepizole, an alcohol dehydrogenase inhibitor used to treat toxic alcohol poisoning, has been suggested for treating DER by preventing the metabolism of ethanol to acetaldehyde. However, its effectiveness and safety have been poorly assessed in this setting. Cases: Ten DER patients (median age, 40 years; 7 males/3 females) were included in the study. DER features consisted of consciousness impairment (median Glasgow coma score, 13; need for mechanical ventilation, 30%) with flushing (50%), vomiting (40%), electrocardiogram abnormalities (30%) and circulatory failure requiring norepinephrine (30%). Patients were successfully treated with a single intravenous infusion of fomepizole (median dose, 7.5 mg/kg). The three patients receiving norepinephrine did not improve until fomepizole was administered. The other seven patients improved promptly following fomepizole infusion without requirement for vasopressor support. All patients fully recovered. Local pain at the injection site was the only reported adverse reaction in one patient. Conclusion: Our case series supports the effectiveness and safety of fomepizole in rapidly reversing DER-induced vasodilatation and toxicity.


This research focuses on developing a method to analyze why-questions.  Some previous researches on the why-question analysis usually used the morphological and the syntactical approach without considering the expected answer types. Moreover, they rarely involved domain ontology to capture the semantic or conceptualization of the content. Consequently, some semantic mismatches occurred and then resulting not appropriate answers. The proposed method considers the expected answer types and involves domain ontology. It adapts the simple, the bag-of-words like model, by using semantic entities (i.e., concepts/entities and relations) instead of words to represent a query. The proposed method expands the question by adding the additional semantic entities got by executing the constructed SPARQL query of the why-question over the domain ontology. The major contribution of this research is in developing an ontology-based why-question analysis method by considering the expected answer types. Some experiments have been conducted to evaluate each phase of the proposed method. The results show good performance for all performance measures used (i.e., precision, recall, undergeneration, and overgeneration). Furthermore, comparison against two baseline methods, the keyword-based ones (i.e., the term-based and the phrase-based method), shows that the proposed method obtained better performance results in terms of MRR and P@10 values.


The American Association of Stratigraphic Palynologists bestows upon SVEIN B. MANUM its Medal of Scientific Excellence for four decades of outstanding contribution to the study of land plant palynology, paleobotany, dinoflagellate cyst morphology and stratigraphy. His power of meticulous observation and scholarly investigation of new fields has been combined with the unique art of blending palynological and paleobotanical observations in evolution, morphology, paleoecology and biostratigraphy.

SVEIN B. MANUM

Professor Svein B. Manum was born in 1926 in Askim, Norway. He received the degree of Cand. real. (M.Sc.) in 1953 and Dr. philos. (Ph.D.) in 1962 from the University of Oslo. His interest had been drawn to the modern and fossil floras of Spitsbergen by a popular book that he had read as a teenager. As a botany student he approached the late Professor Ove Arbo Hoeg, renowned for studies of the Devonian floras of Spitsbergen, to apply for a thesis project related to Spitsbergen. He was offered a palynological study of Spitsbergen's Paleogene coals, which started a lifelong research interest in Arctic fossil floras and paleoclimates.

Svein is outstanding among the palynologists and paleobotanists of his generation. He remains one of the few who has set an example of combining in his research three distinct fields: land plant palynology, dinoflagellate cyst studies, and paleobotany. With this scientific approach Svein has generated new ideas on Spitsbergen's Cretaceous and Tertiary floras, the evolution of the North Atlantic, biogeography and climate change.

In well over 50 publications Svein has consistently set the highest standards of observation and insightful analysis of pollen, dinoflagellate cyst morphology and stratigraphy, and fossil floras of the Arctic. His investigations on clitellate cocoons demonstrate his power of meticulous observation.

At the University of Oslo he has taught students and associates the importance of careful observation and thoughtful interpretation. He …


Background: There is an ongoing debate regarding what dietary pattern is the most effective for breast cancer prevention. Several studies have examined hypocaloric diets with an emphasis on various macronutrient compositions, yielding inconclusive data regarding their effects on weight loss and breast cancer risk reduction. This study examined the effects of a 1-year intervention of 2 calorie-restricted diets (low-fat or low-carbohydrate [LFD and LCD, respectively]), in combination with increased physical activity (PA), on circulating adipokine concentrations among premenopausal women at increased risk of developing breast cancer. Methods: Seventy nine overweight/obese premenopausal women were randomized to a LFD or LCD with PA for 52 weeks. Serum adiponectin, leptin and the adiponectin to leptin ratio (A/L) were measured at baseline, and weeks 25 and 52. Linear mixed models, which included fixed effects of treatment arm, time, and a treatment-by-time interaction, were used to assess intervention effects on serum adipokine concentrations. Results: Compared to baseline, at week 25, adiponectin decreased 4.1% and 2.3%, leptin decreased 30.0% and 35.3%, and the A/L ratio increased 10.5% and 19.4%, among LFD and LCD participants, respectively. Compared to baseline, at week 52, adiponectin decreased 8.5% and 5.0%, leptin decreased 23.0% and 19.7%, and the A/L ratio increased 23.7% and 44.4%, among LFD and LCD participants, respectively. No differences in adipokine changes by diet were observed. Notably, we observed favorable improvement of adipokine concentrations (adiponectin increased 4.4% and 9.5%, leptin decreased 13.0% and 30.1%, and the A/L ratio increased 21.0% and 52.6%, at weeks 25 and 52, respectively) among women who were adherent to the LCD. Conclusion: These findings suggest that long-term caloric-restriction with increased PA can effectively modify the obesity-related adipokines and thus, may prove useful as cancer preventive strategies for premenopausal women. Future studies of larger samples are required to confirm the beneficial effects of these interventions among high-risk women. Citation Format: Adana A.M. Llanos, Jessica L. Krok, Juan Peng, Michael L. Pennell, Susan E. Olivo-Marston, Mara Z. Vitolins, Cecilia R. Degraffinreid, Electra D. Paskett. Effects of low-fat and low-carbohydrate dietary patterns combined with physical activity on serum adipokine concentrations among premenopausal women: A randomized trial. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C45.


Traditional risk evaluation on special equipment primarily used the technical reports of equipment safety performance evaluation, lack consideration of management, staff, equipment and operating environment. Besides, traditional evaluation simply adopted a qualitative or quantitative evaluation method which is not comprehensive and systematic. Based on coordination theory, this paper has constructed a 2-dimensional and 4-level evaluation system, which includes the probability of accidents and the seriousness of its consequences. The evaluation of accident probability emphasizes the coordination of the "management - staff - equipment - environment" system, while the evaluation of the seriousness emphasizes the comprehensiveness of the influencing factors. In addition, we use both quantitative and qualitative evaluation methods to make the results more credible, and propose the classified management method, which helps companies develop appropriate solutions to prevent accidents effectively.


Objective:This study, lasting up to 90 days, was undertaken in patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy (nonsteroidal anti-inflammatory drugs, acetaminophen, and/or short-acting opioids) to evaluate functional outcomes, as well as efficacy and safety, of controlled-release oxycodone versus placebo. Methods:One hundred seven patients received either controlled-release oxycodone or placebo every 12 hours in this double blind, randomized, placebo-controlled, parallel-group study. Stable previous regimens of acetaminophen or nonsteroidal anti-inflammatory agents were allowed to continue. Primary efficacy variables included Brief Pain Inventory average pain intensity scores at completion of initial titration, Western Ontario and McMaster Universities Osteoarthritis Index scores at days 30 and 60, and the percentage of patients discontinuing due to inadequate pain control. Results:Controlled-release oxycodone was significantly superior to placebo in decreasing average pain intensity and in reducing pain-induced interference with general activity, walking ability (except at day 30), and normal work, as well as mood, sleep, relations with people (at days 60 and 90), and enjoyment in life. Daily functioning, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index, was also significantly improved in the controlled-release oxycodone group. In the placebo group, a significantly greater percentage of patients discontinued due to inadequate pain control. Adverse events were consistent with opioid adverse events, and no safety concerns were noted. Discussion:Treatment with controlled-release oxycodone of patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy resulted in significant pain control and improvements in physical functioning.


Most of the metallic devices have to be removed, treating osteochondritis dissecans lesions. This animal study describes the biological and mechanical behavior of screws and pins, made of commercially available PGA/PLA and PLA96 and metallic screws and pins, used for fragment fixation. A sham operation served as control. A tissue reaction with cavity formation was observed around every PGA/PLA screw, beginning at 12 weeks following insertion, in contrast to once around a PLA96 screw (p < 0.001), once around one of the 16 PGA/PLA pins and never around those, made of PLA96 (no significance). Disintegration of the PGA/PLA devices started 6 weeks following implantation against 34 weeks for the PLA96 implants. The gap between the fragment and the recipient cartilage disappeared only in the sham group. Many fragments of PGA/PLA material were found in the synovia, in contrast with just a few fragments in the PLA96 group, causing a mild cellular reaction. No polymer particles were found in the draining lymph nodes at any interval. In conclusion, the tested biodegradable screws should not be used for fragment fixation in the treatment of osteochondritis dissecans. Either an undesirable tissue reaction can be expected (PGAPLA), or, because of the slow degradation (PLLA), a screw might damage the opposite cartilage during weight bearing. Two biodegradable pins provide a safe rotational stability and should be combined with one metallic screw, providing compression. This screw has to be removed before loading the limb to prevent cartilage wear of the opposite tibia plateau.


Background Due to the ongoing COVID-19 pandemic, various host countries such as Singapore, imposed entry requirements for migrant workers including pre-departure COVID-19 seroconversion proof. To combat COVID-19 worldwide, several vaccines have acquired conditional approval. This study sought to assess antibody levels after immunization with different COVID-19 vaccines among the migrant workers of Bangladesh. Methods Venous blood samples were collected from migrant workers who were vaccinated with different COVID-19 vaccines (n=675). Antibodies to SARS-CoV-2 spike protein (S) and nucleocapsid protein (N) were determined using Roche Elecsys® Anti-SARS-CoV-2 S and N immunoassay, respectively. Results All participants receiving COVID-19 vaccines showed antibodies to S-protein, while 91.36% were positive for N-specific antibodies. The highest anti-S antibody titers were found among the workers who completed booster doses (13327 U/mL), received mRNA vaccines Moderna/Spikevax (9459 U/mL) or Pfizer-BioNTech/Comirnaty (9181 U/mL), and reported SARS-CoV-2 infection in the last six months (8849 U/mL). The median anti-S antibody titers in the first month since the last vaccination was 8184 U/mL, which declined to 5094 U/mL at the end of six months. A strong correlation of anti-S antibodies was found with past SARS-CoV-2 infection (p < 0.001) and the type of vaccines received (p <0.001) in the workers. Conclusion Bangladeshi migrant workers receiving booster doses of vaccine, vaccinated with mRNA vaccines, and having past SARS-CoV-2 infection, mounted higher antibody responses. However, antibody levels waned with time. These findings suggest a need for further booster doses, preferably with mRNA vaccines for migrant workers before reaching host countries. Graphical Abstract


Although traditional software engineering focuses on development Component-based software engineering (CBSE) processes must focus on integration. In this paper, we elaborate on this focus into a process framework for CBSE consisting of four major activity areas: engineering, business, management, and overarching. We show how these activities are concurrent with respect to an iterative and incremental development model. Detailed discussions are also presented on the consequent issues, concerns, problems, and recommended solutions.


Purpose Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. Materials and Methods A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. Results A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. Conclusion Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation.


Chronic obstructive pulmonary disease (COPD) is a chronic disease that causes high morbidity and mortality. In the Lazio Region, the Clinical Pathway (PDTA) for COPD was codified in 2016. An analysis of the medical records of a retrospective open cohort of 77 patients followed at the Outpatient Clinic Torrenova (ASL Roma 2) from 2017 to 2021, for a total of 305 visits, was performed. The mean interval between visits per individual patient was 169±124 days, the overall length of follow-up 613±388 days. The mean age of patients enrolled in the PDTA was 67 years, 90% were smokers or former smokers, and 30% had major comorbidities. At the first visit, 13% of the patients had normal spirometry, 36% mild obstruction (GOLD 1), 13% GOLD 2, 15% GOLD 3 and none GOLD 4. Regarding ABCD classification, 29% of the patients were compatible with class A, 3% with class B, 29% class C and 10% class D. The analysis of the severity of the patients through a composite score showed a Gaussian distribution of patients at the first visits, a positive correlation with the number of follow-ups and a negative correlation with the interval of follow-up visits; the overall length of follow-up did not correlate with the severity of the disease. The active COPD PDTA in ASL Roma 2 seems to hit the target of taking care of the patient in the early stages of the disease. The effects of early intervention on disease outcomes should be highlighted by further studies.


The active site of human immunodeficiency virus reverse transcriptase (HIV1-RT) was probed using three group-specific reagents: phenylglyoxal (PG), N-ethylmaleimide (NEM), and pyridoxal 5'-phosphate (PLP). The inactivation of HIV1-RT by arginine-specific PG was found to be completely protected against by adding primer-template. The potential active site arginine was localized to position 277 in the primary structure, suggesting that the polymerase domain of the enzyme should be considered as extending at least this far from the N terminus. The sulfhydryl-modifying reagent NEM completely inhibits NY5-HIV1-RT, which contains a cysteine at position 162, and such inhibition is protected against by primer-template. However, it does not strongly inhibit LAV-HIV1-RT, in which C162 is replaced by S162, indicating that while C162 may be at or near the active site or interact allosterically with primer-template, it is not essential for activity. The lysine-specific reagent PLP was found to be a noncompetitive inhibitor with respect to both primer-template [poly(rA).oligo(dT)] and dTTP. The latter result differentiates HIV1-RT from other RTs, for which PLP has been shown to be a competitive inhibitor with respect to dTTP.


The authors report eight cases of intussusception of small and large intestine in adults during five years. 3 of the intussusception caused by simple tumors in five cases by malignant. In three cases were chronic presented long term signs and symptoms. Ileo-ileal invagination was diagnostised at 3 patients, ileo-caecal in one case and ileocolic intussusception also in one case. In 2 cases developed caeco-colic, in one case colo-colic invagination. Resection was strongly indicated in seven cases and wedge resection was done at the last patient. One patient has died of cerebral multiple embilization. They review the etiology and pathology, the signs and symptoms as well as the difficulties during diagnosis and treatment of the intussusceptions according to their own experience and literary datas. The authors draw the attention to the importance of the modern iconographic, tools, particularly the ultrasonography in the diagnosis of intussusception.


Abstract Mercury exposure in pregnancy has been associated with both pregnancy complications and developmental problems in infants. Apart from industrial accidents and contaminated food, mercury exposure is likely to arise from predatory fish consumption, environmental contamination and dental amalgam restorations placed before or during pregnancy. It would be prudent to recommend that pregnant women avoid these potential problems and minimize any risk. The available literature indicates a linear relationship with mercury levels and IQ deficit, and therefore a safe limit of mercury cannot be calculated.


As the basis of competition increasingly depends on the quality of knowledge assets of companies, to sustain competitive advantage, companies must develop critical organisational knowledge. In this paper issues related to utilising knowledge within a company are investigated using a case study. Key findings of the study are outlined, and a framework is proposed to assist organisations in building critical organisational knowledge.


Vesicoureteral reflux (VUR) is the most common anomaly associated with duplex systems. In addition to an uncomplicated duplex system, reflux can also be secondary in the presence of an ectopic ureterocele with duplex systems. Controversy exists in regard to the initial and most definitive management of these anomalies when they coexist. This paper will highlight what is currently known about duplex systems and VUR, and will attempt to provide evidence supporting the various surgical approaches to an ectopic ureterocele and duplex system and the implications of concomitant VUR.


Diplodia pinea, an opportunistic and latent pathogen, can significantly affect Pinus productivity worldwide. Despite being studied in South Africa for almost 100years, the source of D. pinea inoculum responsible for seedling infection is unknown. The aim of this study was to determine the role of seed in vertical transmission of D. pinea and to investigate sources of inoculum leading to horizontal transmission to pine seedlings. Surface-disinfected seeds were inoculated with spore and mycelium suspensions of D. pinea to determine its effect on germination. In addition, isolation of the fungus was performed from surface-disinfected seeds, asymptomatic seedlings collected from nurseries, plantations where pines naturally regenerate and recently established fields, to assess transmission and incidence of endophytic D. pinea infections. Inoculation of seeds with D. pinea spore suspensions affected speed and rate of germination. The fungus was isolated from surface-disinfected seeds in only a few instances (2-3%) and was not found in healthy seedlings collected from greenhouses and nurseries, suggesting that vertical transmission of the fungus does not occur or is rare. In contrast, D. pinea was isolated from 40% of seedlings obtained from the understory of mature P. patula trees showing that horizontal transmission from mature to young trees sustains the D. pinea inoculum in South African pine plantations.


Environmental planning disputes often combine questions of regulation and legislation with distinctive, place-based epistemic issues that lend themselves to citizen science approaches. Whilst these citizen science activities often concern the enforcement of regulations, here we describe the attempts of a local community group to prevent the start-up of a new biomass incineration plant by showing that it fails to comply with the relevant regulations and/or that the associated legislation has not been applied correctly. Through documentary sources and in-depth interviews, we examine the ways in which the group's work has parallels with aspects of regulatory science. In describing this work, and thinking about how to categorise it, we argue that conceptions of citizen science need to be broadened to include a wider range of activities than the traditional focus on primary data collection.


An interpretation of the collisionality dependence of , which has been observed in many tokamaks, is presented in terms of neoclassical tearing mode theory. Magnetic islands are predicted to be driven to large saturated widths by the perturbed bootstrap current, provided their width exceeds a certain threshold value. This width is of the order of the ion banana width for low collisionality plasmas, but is substantially larger in collisional plasmas (though still within the banana regime); below this threshold value the stabilizing ion polarization current causes an island to decay. Assuming that `background' MHD events such as ELMs or sawteeth can provide an initial `seed' magnetic island of width (through toroidal coupling, for example) one can develop a model equation which retains the essential properties of neoclassical tearing mode theory and is able to reproduce many of the experimental trends associated with the reduced -limit.


Summary form only given. We have demonstrated a widely-tunable, 2.5 Gb/s transmitter based on a SG-DBR laser monolithically integrated with a SOA and electroabsorption modulator. Time-averaged powers in excess of 3 dBm and RF extinction ratio >10 dB across a 40 nm tuning range have been achieved. Error-free transmission at 2.5 Gb/s has been demonstrated for 200 km of standard single mode fiber.


In this chapter, I review the contributions of scholars and activists who share my concern that the legal and social contexts that typically inform the formation of Indigenous-industry agreements in Latin America are marked by enormous power disparities and stark epistemological differences. This literature review supports the proposition that it is likely that many Indigenous-industry agreements in Latin America lack legitimacy and perhaps legality. This in turn raises serious questions about whether or not Indigenous-industry "agreements" formed in these conditions could possibly rest on any meaningful notion of consent. I make this important point in order to focus on a narrower question, one of the present but also very much one of the future, as we face the aftermath, in the years and decades to come, of the proliferation of agreements under present circumstances. What happens when a community mobilizes in order to challenge the legality of a past agreement with industry, such as for example by contesting the idea that it actually consented? What if the company and/or the state holds up a document with signatures from past community leaders that allegedly represent consent? If the company and the state are unresponsive to a community's concerns about an agreement, can it resort to the courts? In this chapter, I explore some of these questions by referring to Peru as a case study. In my conclusion, I explore the significance of this study for ongoing normative developments in relation to Indigenous peoples' right to consultation, consent and the formation of Indigenous-industry agreements.


BACKGROUND & AIMS
Up-regulation of vascular endothelial growth factor is known to play a critical role in hepatocellular tumor biology. In an attempt to identify factors responsible for vascular endothelial growth factor induction in human hepatocellular carcinoma, we evaluated the effects of activin A, a member of the transforming growth factor-beta cytokine superfamily, on vascular endothelial growth factor gene expression.

METHODS
Expression of vascular endothelial growth factor, activin A, and its receptors was analyzed by immunohistochemistry, polymerase chain reaction, and enzyme-linked immunosorbent assay. Functional vascular endothelial growth factor promoter analysis and gel shift assays were performed to define minimal promoter requirements and potential transcription factors. Nuclear expression and biochemical modifications of Sp1, as well as subcellular distribution, expression, and physical interaction of Smad proteins with Sp1, were assessed with immunoprecipitation and Western blot analysis.

RESULTS
Hepatocellular carcinoma tumors and cell lines expressed activin A and its receptors. Activin A stimulated vascular endothelial growth factor gene transcription through Sp1-dependent induction of vascular endothelial growth factor promoter activity. Furthermore, activin A stimulated the DNA-binding and transactivation potential of Sp1. Immunoprecipitation showed activin A-dependent nuclear translocation of Smad2 and induction of Sp1/Smad2 interaction. The functional relevance of Sp1/Smad2 interaction was confirmed by transient transfection experiments, which showed that overexpression of Smad2 increased vascular endothelial growth factor promoter activity and endogenous vascular endothelial growth factor protein expression, whereas dominant negative Smad2 blocked activin A responsiveness.

CONCLUSIONS
This study identifies activin A as a novel stimulus of vascular endothelial growth factor gene expression in hepatocellular carcinoma and delineates physical and functional cooperation of Sp1 and Smad2 as the underlying mechanism.


Systemic mastocytosis is a rare disorder characterized by clonal proliferation, which results in abnormally high numbers of mast cells in the skin, bone marrow, and internal organs, such as liver, spleen, or lymph nodes. Mast cell leukemia and subvariants were stratified by the World Health Organization in 2016, as a subtype of systemic mastocytosis. Here, we present a case of acute mast cell leukemia that was imatinib-sensitive, with well-known mutations in the oncogene, KIT (c.1565 T > G p.Phe522Cys), and in the splicing factor gene, SF3B1 (c.2098 A > G, p.Lys700Glu). Molecular cytogenetic studies showed that 26% of cells harbored the 46,XX,der(5)t(5;6)(q35;q24),t(10;16)(q26;q23) karyotype abnormality, confirmed with the fluorescence in-situ hybridization technique. Additionally, the patient showed severe hepatosplenomegaly with multiple retroperitoneal, mesenteric, and axillary adenopathies. Although the prognostic survival of patients with mast cell leukemia is around 6 months, this rare case, with a low-frequency (< 5%) p.Phe522Cys KIT mutation, was associated with complete remission and negative minimal residual disease, which lasted for 2.5 years; moreover, the mutation was not detectable after imatinib treatment. When the patient relapsed, the two mutations studied in KIT and SF3B1 genes reappeared, and a new clone emerged with the variant c.2465 A > C p.Asn822Thr, located in the activation loop of the KIT protein. Molecular analyses of the KIT gene were essential for selecting the appropriate tyrosine-kinase inhibitor. Accurate drug selection can prevent possible resistance and facilitate adequate treatment of subsequent relapses.


The adoption of recommender systems in online news personalization has made it possible to tailor the news stream to the individual interests of each reader. Previous research on commercial recommender systems has emphasized their use in large-scale media houses and technology companies, and real-world experiments indicate substantial improvements of click rates and user satisfaction. It is less understood how smaller media houses are coping with this new technology, how the technology affects their business models, their editorial processes, and their news production in general. Here we report on the experiences from numerous Scandinavian media houses that have experimented with various recommender strategies and streamlined their news production to provide personalized news experiences. In addition to influencing the content and style of news stories and the working environment of journalists, the news recommender systems have been part of a profound digital transformation of the whole media industry. Interestingly, many media houses have found it undesirable to automate the entire recommendation process and look for approaches that combine automatic recommendations with editorial choices.


Objective:To evaluate treatment response, durability and tolerance of a four-drug regimen including saquinavir and ritonavir in combination with either zidovudine/lamivudine or stavudine/lamivudine. Design:Observational cohort of HIV-positive individuals. Methods:Viral load, CD4+ and CD8+ T lymphocyte counts were assessed at intervals of 1–3 months in subjects commencing therapy between July 1996 and November 1996. Adverse events were evaluated as well as risk factors for therapeutic failures. Results:A group of 56 male patients were included and followed for 48 weeks. Of these, 66% had already taken a protease inhibitor. Viral load dropped by a median 1.98 log10 HIV RNA copies/ml from baseline (interquartile range: 1.49–2.46) and became undetectable (< 400 copies/ml) in 68% of patients. Response varied: 9% were non-responders (HIV RNA reduction < 0.5 log10 copies/ml) and 23% were incomplete responders (nadir of HIV RNA > 400 copies/ml). After 48 weeks, viral load remained undetectable in 49%. Median CD4+ T lymphocyte count increased from 191 × 106 to 418 × 106 cells/l (range, 241–537 × 106 cells/l). Although protease inhibitor and nucleoside pretreatment selected for drug-resistant viral mutants, only the protease inhibitor experience was identified as a risk factor for therapeutic failure. Adverse events occurred in 73% of patients and led to a change of therapy in 9%. Conclusion:Despite advanced HIV disease and pretreatment with multiple antiretroviral drugs, a strong initial treatment response to this drug regimen was observed. However, virological failure occurred in 51% of patients after 48 weeks and frequent adverse events complicated therapy. © 1998 Lippincott Williams & Wilkins


Reported is a case of a 39-year-old Caucasian man who presented to the emergency department with sudden onset bilateral lower extremity paralysis after consuming a large amount of carbohydrates and alcohol. A CT, MRI, and lumbar puncture were performed with negative results; lab results showed hyperthyroidism and hypokalemia. The patient was diagnosed with thyrotoxic periodic paralysis. In a patient presenting with sudden onset paralysis and hypokalemia, the emergency physician should include thyrotoxic periodic paralysis in the differential diagnosis and focus on treating and working up the hypokalemia instead of the paralysis.


PURPOSE
To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities.

METHOD
In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed.

RESULTS
Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P<0.01; M1-1: P<0.01) and high-grade anti-angiogenetic toxicities (APA: P = 0.034; P<0.05), including hypertension, proteinuria and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P<0.001) and M1-1 (P<0.01) while CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P<0.01).

CONCLUSION
Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need considering in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. Significance Statement Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.


In order to solve the traditional manipulator dynamics simulation problems of low efficiency and bad real-time, a method of manipulator dynamics simulation based on ODE is proposed. First of all, in order to obtain the kinematics model, the building of manipulator D-H coordinate system is necessary. Secondly, the calculation of manipulator inverse kinematics is performed by Euclidean norm. Thirdly, manipulator dynamics calculation is accomplished by open-source dynamics engine Open Dynamic Engine. At last, the 3D simulation platform of manipulator is established after importing 3D model of manipulator into Open Inventor. The simulation experiment shows that the method has high computing efficiency, it not only can realizes the real-time control of manipulator, but also can draws the curves of dynamics parameters. The experiment demonstrates that this method is effective and can be applied to real-time dynamic simulation of robot manipulator.


Background Guidelines recommend chlamydia screening of sexually active young women. Screening rates have increased over the past 10 years, but remain low. Current data used to monitor chlamydia testing trends and positivity rates have limitations, for example, national surveys provide representative data but are cross sectional and use small sample sizes, so longitudinal and subgroup analyses are not possible. To monitor trends more effectively, we solicited chlamydia testing data from commercial laboratories to obtain a representative sample of the US market. Methods Demographic characteristics of persons tested, their geographic location, assay types, specimen sources, and test positivity by sex, age, and insurance type were assessed for all chlamydia testing performed by this laboratory corporation during June 2008–July 2010. Results The dataset contained 3.26 million specimen records. Among those tested, 86.2% were women, 41.0% were aged 15–24 years, 73.5% had commercial insurance, 21.8% had Medicaid insurance, and 56.6% resided in the South. The most frequently used type of chlamydia test was a nucleic acid amplification test (77.5%). Among women, 59.7% of specimens were cervical, 21.1% vaginal, and 18.8% urine. Overall, 4.0% of tests were positive. Positivity rates were highest in persons aged 15–19 years, and higher in men than women for all age groups. Rates also were higher in women with Medicaid insurance than women with private insurance. Conclusions Systematically collected laboratory data can fill a critical gap in monitoring US chlamydia testing and positivity trends. These data are more representative of the US population by geographic distribution and insurance type than other data sources. The analysis of laboratory testing data might be useful for national surveillance that would not be dependent on provider or health department reporting. Our findings underscore the importance of screening young women for chlamydia, especially adolescents in whom screening rates are low. Men had higher positivity rates probably because they sought treatment for symptoms or were referred by an infected partner. Further analysis is needed to assess if testing of persons older than 25 years was according to guidelines, such as pregnant women, at-risk persons, or symptomatic persons.


This paper presents a section of the findings of a case study of a newly established community rehabilitation team (CRT) comprising physiotherapists, occupational therapists and nurses. The findings reported here address issues of interdisciplinary teamwork that arose during the project. All eight members of the team were interviewed as well as three ex-team members. The data were collected by semi-structured interviews and analysed using thematic content analysis (Strauss and Corbin, 1990). The findings suggest that when recognized barriers to teamwork are eradicated, such as geographical separation and different employers, teams such as the CRT can achieve high levels of teamwork. A problem that took longer for the CRT to resolve, however, was that of flexible working across traditional professional and hierarchical role boundaries. The paper concludes that the difficulties that need to be overcome when a new team and new service are established concurrently, should not be underestimated.


The software engineering community is striving to handle a significant number of new critical demands. Productivity, quality, and runtime flexibility are only few of them. To satisfy such requirements, new development paradigms are regularly proposed. Service-Oriented Computing (SOC) is one of them. SOC is based on the notion of services, which are well-defined composition units, to support rapid application development. This chapter presents a brief state of the art of services. Although SOC brings properties of major interest, it suffers from usual limitations of reused-based approach. In particular, service composition is much more complicated than often pretended. In this chapter, we propose to present a model-driven approach to service composition dealing with non-functional aspects, including security.


Background : Symptoms of most common bacterial and parasitic sexually transmitted infections tend to be non-specific and typically have a variety of different potential causal agents that may require different treatments. In this field the pathogenic potential of genital Ureaplasma species is still uncertain and debated. The goal of this study was to investigate the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) in a cohort of symptomatic and asymptomatic childbearing age women and to assess the relationships between bacterial vaginosis and symptoms with both UU and UP. Materials and Methods : DNA of 2735 endocervical specimens was consecutively analysed by a commercial multiplex real-time polymerase chain reaction for detection of 7 multiple target sequences simultaneously: CT, NG, TV, MG, MH, UU and UP. Results : Out of the total number of population studied (n=2735), UP was found to be the species with highest prevalence (30.9%) followed by MH (6.5%), UU (6.3%), CT (2.6%), MG (0.8%) and TV (0.9%). UP single species detection was extremely significant in symptomatic women with normal flora (P<0.0001). The correlation of UP in symptomatic women with bacterial vaginosis was not significant (P=0.3387). Conclusions : Our results suggest a potential specific etiological role to UP, still considered rightly or wrongly innocent bystander , despite the lack so far of specific-species culture tests.


The Galactic Center shows evidence for the presence of three important AGN ingredients: a Black Hole ($M_\bullet\sim10^6M_\odot$), an accretion disk ($10^{-8.5} - 10^{-7} M_\odot/{\rm yr}$) and a powerful jet (jet power $\ge$ 10\% disk luminosity). However, the degree of activity is very low and can barely account for the energetics of the whole central region. Neverthelss, in the very inner arsecond the central engine becomes dominant and provides an interesting laboratory for the physics of central engines (Black Holes) in galactic nuclei. We therefore give an overall picture of the central arcsecond where we link the radio emission and the heating of the ambient medium to a weakly accreting disk surrounding a massive Black Hole. >>


In this paper, a microscopic 3D image is reconstructed for a micro-manipulation system. The 3D image reconstruction is based on a binocular stereo vision system. We propose a new method called "support value" to solve correspondence problems. Geometric constraints are added to reduce the ambiguities in stereo matching. Left/right consistency check is used to increase the confidence for matching results. Post-processing helps remove the outliers and make original dense disparity map smooth and reliable. The three-dimensional characteristics can be reconstructed by perspective projection. Finally, the 3D image reconstruction algorithm is successfully applied to a micro manipulation system for cell image reconstruction by a simpler and more friendly way.


Electronic business (e-business) plays a major role in the modern economic network due to shorter cycle time and faster information transactions. Building enterprise applications that can coordinate activities, decisions, and knowledge cross many functions is a good solution for e-business. Hence, how to implement enterprise applications successfully has become an increasingly important management issue. Although information systems (IS) success has received fairly extensive attention from prior research, issues regarding whether service delivered by systems can be justifiably relied by users are seriously ignored, especially for complex systems like enterprise applications. Thus, this paper attempts to extend this kind of concept, perceived dependability, into the DeLone & McLean's IS success model for exploring how it influences enterprise applications success. Results from a survey of 170 respondents taken from six international e-businesses in Taiwan strongly support that dependability is indeed an important factor for enterprise applications success. Additionally, over and beyond the effects of dependability on enterprise applications success, it can help practitioners and managers get deep insights about how to implement e-business successfully


In this paper, first the operating principles of a non-isolated universal bidirectional DC-DC converter are studied and analyzed. The presented power converter is capable of operating in all power transferring directions in buck/boost modes. Zero voltage switching can be achieved for all the power switches through proper modulation strategy design, therefore, the presented converter can achieve high efficiency. To further improve the efficiency, the relationship between the phase-shift angle and the overall system efficiency is analyzed in detail, an adaptive phase-shift (APS) control method which determines the phase-shift value between gating signals according to the load level is then proposed. As the modulation strategy is a software-based solution, there is no requirement for additional circuits, therefore, it can be implemented easily and instability and noise susceptibility problems can be reduced. To validate the correctness and the effectiveness of the proposed method, a 300 W prototyping circuit is implemented and tested. A low cost dsPIC33FJ16GS502 digital signal controller is adopted in this paper to realize the power flow control, DC-bus voltage regulation and APS control. According to the experimental results, a 12.2% efficiency improvement at light load and 4.0% efficiency improvement at half load can be achieved.


In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality's existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality-we stratify nanomaterials on the basis of their (i) magnetic, (ii) optical, (iii) acoustic, and/or (iv) nuclear properties. We evaluate them for their ability to provide relevant information under preclinical and clinical circumstances, their in vivo safety profiles (which are being incorporated into their chemical design), their modularity in being fused to create multimodal nanomaterials (spanning multiple different physical imaging modalities and therapeutic/theranostic capabilities), their key properties, and critically their likelihood to be clinically translated.


In this paper, a new type of a neuromorphic single-electron(SE) circuit is described and its operation is also evaluated by conducting Monte Carlo simulation. The circuit is expected as a new information-processing device. However, it is known that the circuit is very sensitive to noise and fluctuation, so that we have studied how to overcome such noise effect. Recently, unique technique that imitates stochastic resonance (SR) behavior in neural networks has been proposed to solve the problem of noise. We focus on internal noise for the SR system. To confirm the SR phenomenon caused by the internal noise, we change the circuit form to a circular structure. We can construct the circular neural network by using the SE circuit because the operation of them is similar to neurons. The proposed SE circuit network was able to show the SR phenomenon. Moreover, the circuit we found could amplify the output signal.


In this paper, an SCA based HF waveform implementation on an own developed single board computer hardware (GÖMSİS) is presented. The JTRS program in the United States is developing the SCA Standard which defines the specifications for new generation software defined radios. The software defined radios are expected to gain great flexibility and reconfigurability by the help of this standard. In this study, an SCA based HF modem application has been developed and ported to our own platform. The lessons learned from the design and implementation of an SCA based waveform are presented. NATO STANAG 4285 HF modem is selected to be the target waveform in this work.


The cytotoxic agent docetaxel not only has proven activity in non-small cell lung cancer-when used alone or in combination-but is also a potent radiosensitizer, and improved treatments are needed in all stages of this disease. In patients with locoregionally advanced (stage III) disease, docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy/surgery. Presently, therapeutic gains appear to be maximized by the use of concurrent chemotherapy and irradiation. This review focuses on research with combinations of docetaxel with either cisplatin or carboplatin and radiotherapy. Overall response and survival rates to date provide data worth pursuing. From phase I data, weekly docetaxel at 20 mg/m(2) plus cisplatin at 25 mg/m(2) or carboplatin to an area under the concentration time curve of 2 mg/ml*min with concurrent radiotherapy to 60 Gy over 6 weeks appear to be suitable for phase II trials. Predominant toxicities are esophagitis and neutropenia, but a low frequency of pulmonary toxicity is reported. Induction, concurrent, and consolidation docetaxel-based chemoradiotherapy in potentially resectable disease are all being investigated. Future research could include the investigation of computed tomography/ positron emission tomography-derived target volume radiotherapy, dose-escalated therapy, and alternative fractionation schedules in combination with docetaxel-based cytotoxic chemotherapy.


Accurate and complete genetic classification of AML is crucial for the prediction of clinical outcome and treatment stratification. Deciphering the spectrum of genetic abnormalities by polymerase chain reaction (PCR), karyotyping and fluorescence in situ hybridization (FISH) in routine diagnostics is the current gold standard, however, fusion genes might potentially be missed by these assays. Recently, several methods have been developed to improve the detection of gene fusion transcripts based on RNA sequencing data, providing robust results.
 To test the detection power and assess the applicability of RNA-Seq based methods in clinical diagnostics we applied two different algorithms, namely FusionCatcher (Nicorici D et al., bioRxiv, 2014) and Arriba (Uhrig S et al., DKFZ, https://github.com/suhrig/arriba), to the transcriptomes of 895 well-characterized AML samples from three independently sequenced cohorts: AMLCG (Herold T et al., Haematologica, 2018, n=261), DKTK (Greif PA et al., Clin Cancer Res, 2018 and unpublished data, n=166), BeatAML (Tyner JW et al., Nature 2018, n=468) and publicly available healthy control samples (SRA studies: SRP018028, SRP047126, SRP050146, SRP105369, SRP115911, SRP133442, n=38).
 According to karyotyping, 31% (277/895) of samples harbored chromosomal aberrations putatively causing gene fusions (i.e. translocations, interstitial deletions, duplications, inversions, insertions). Analyses by FISH and/or PCR confirmed these rearrangements in 51.3% (142/277) of samples, whereas fusion detection by the means of RNA-Seq showed evidence for fusion genes corresponding to these rearrangements in 60.3% (167/277) of samples. Chromosomal aberrations, identified by karyotyping, which are known to result in clinically relevant fusions (e.g. RUNX1-RUNX1T1, KMT2A fusions) were confirmed by FISH/PCR (AMLCG: n=27/27, DKTK: n=21/21, BeatAML: n=54/57) and RNA-Seq based methods (AMLCG: n=17/27, DKTK: n=21/21, BeatAML: n=56/57) in most of the cases. Of note, the AMLCG cohort was sequenced using the SENSE mRNA Library Prep Kit from Lexogen which seems to be not optimal for fusion detection. Furthermore, 19 samples (AMLCG: n=12, DKTK: n=4, BeatAML: n=3) were found to harbor known pathogenic fusions, described in previous studies, which were not reported by routine diagnostics: NUP98-NSD1 (n=11); CBFB-MYH11, RUNX1-RUNX1T1 and DEK-NUP214 (n=2 each); RUNX1-CBFA2T2 and RUNX1-CBFA2T3 (n=1 each). Reanalysis of six of these samples by PCR confirmed three fusions which were initially missed by routine diagnostics.
 In general, the amount of reported fusion events by RNA-Seq is high (on average 69 and 39 per sample as detected by FusionCatcher and Arriba respectively), even after applying the built-in filters, indicating a high false positive rate. To robustly identify putative novel fusions, we developed a filtering pipeline and incorporated two new filtering steps. The promiscuity score (PS) of a fusion measures the amount of further distinct fusion partners which were detected in the respective cohort for the 5' and 3' gene. The fusion transcript score (FTS) measures the relative abundance of a fusion transcript to its 5' and 3' partner gene. PS and FTS of known, clinically relevant fusions confirmed by FISH/PCR were used to define cut-offs. To further maximize specificity while maintaining sensitivity, we excluded fusion events which we detected in publicly available healthy samples and subsequently filtered for overlapping calls from FusionCatcher and Arriba (Fig. 1A). Additionally, we obtained further evidence for a fusion event by an elevated transcription of the 3' fusion partner. In case of a fusion event, the transcription of the 3' partner gene likely gets under the control of the promoter of the 5' partner gene. This results in an elevated transcription of genes which are otherwise transcribed at low levels (Fig. 1B-C). Thus, we identified five putatively novel recurrent fusion genes which were detected in two cohorts independently: NRIP1-MIR99AHG, LATS2-ZMYM2, ATP11A-ING1, MBP-SLC66A2, PRDM16-SKI (Fig. 1D-F). Although these events were called with high evidence, we aim at independent validation by complementary methods.
 In our study, we have not only demonstrated that the application of RNA-Seq to the detection of fusion genes is a valuable complement to diagnostic routine but also has the potential to discover novel putatively pathogenic fusions.

 No relevant conflicts of interest to declare.


Background. Spinal cord injuries are one of the main causes of disability in Poland and in the world. Quadriparesis, limitations in activities of daily living, lack of full autonomy and psycho-social problems are consequences of cervical spinal cord injury. Due to the consequences, especially motor paralysis and sedentary lifestyle resulting from spinal injuries, much attention is drawn to physical activity in subjects with this type of injuries. Objective. The aim of the study is to assess the effect of regular physical activity on functional fitness and independent existence of subjects after high spinal cord injury.Methods. 80 subjects with transverse injury of cervical spinal cord were enrolled in the study. The study group included men aged 20-50, in which group 40 (50%) of the subjects were qualified to the physically active group – subjects doing wheelchair sport, and 40 (50%) of the subjects were qualified to the physically inactive group – subjects taking no physical activity. The physically active men were qualified on the basis of their participation in organised activities - wheelchair rugby. Minimum participation was 90 minutes a day twice a week. Subjects from the physically inactive group had a passive lifestyle and participated in no sports activities. Results. Highly significant differences were observed during the study between the physically active and inactive men with regard to the functionality status. The study subjects taking regular physical exercise had better results in all assessed activities. The biggest differences were observed in the field of toilet and dressing up. Conclusions. The study confirmed that regular physical activity is correlated with better fitness. The study also showed that the subjects playing wheelchair rugby are more independent, which results in their better functional status in everyday life.


ABSTRACT Security of water distribution systems is of highest importance to public health. In this study, a novel dynamic hydrant flushing strategy is developed to remove the injected contamination mass in the shortest possible time after being detected by the sensors. The coupled EPANET-IHS simulation-optimization model is developed to determine the hydrant flushing strategies (the hydrant sets and their opening/closing time). This allows water utility managers to utilize the hydrants instantly after the sensor alarm with no need for excessive investigations, which enhances the flushing effectiveness. Developed based on thousands of contaminant injection scenarios (contamination events), the proposed hydrant flushing strategies are reliable to remove any injected contamination mass. Moreover, the operation of hydrant sets is dynamically validated by closing/opening of hydrants throughout the total hydrant flushing duration, which enables the model to flush up to more 20%. The methodology is examined on the mid-sized WDS of Mesopolis city.


Abstract. An observation-based method (OBM) is developed to investigate the sensitivity of ozone formation to precursors during two persistent elevated ozone episodes observed at 77 stations in Guangdong. Average OH concentrations derived at the 77 stations between 08:00 and 13:00 local time stay within a narrow range of 2.5 × 106 cm−3 to 5.5 × 106 cm−3 with a weak dependence on the NOx. These values are in good agreement with OH values observed at a rural station in Pearl River Delta (PRD) and a box model constrained by the ambient conditions. They also agree well with a box model constrained by the ambient conditions observed during the two episodes. The OBM has been used to evaluate the ozone production efficiency, ε(NOx or VOC), defined as the number of O3 molecules produced per molecule of NOx (or VOC) oxidized. Average values of ε(NOx) and ε(VOC) determined by the OBM are 3 and 2.1 ppb/ppb, respectively, both compared well with values in previous studies. Approximately 67 % of the station-days exhibit ozone formation sensitivity to NOx, approximately 20 % of the station-days are in the transitional regime sensitive to both NOx and VOC, only approximately 13 % of the station-days are sensitive to VOC. These results are in semi-quantitative agreement with the ozone formation sensitivity calculated by the box model constrained by ambient conditions observed during the two episodes. However, our OBM results differ from those of most previous investigations which suggested that limiting the emission of VOC rather than NOx would be more effective in reducing ozone reduction in Guangdong.


The purpose of this study was to compare the stability and force of ultimate failure of the acromioclavicular joint (ACJ) after direct arthroscopic distal clavicle excision (DCE) through superior portals and indirect arthroscopic DCE through inferior portals in paired cadaveric shoulders. Ten paired saline-embalmed cadaveric shoulders were operated alternatively using the indirect and direct technique. Biomechanical testing was performed in the horizontal plane, testing displacement at 15N and 30N and finally failure strength was measured testing the constructs until failure occurred. There was a significant difference in failure strength with the direct DCE being stronger: 766.6 N (SD 233.5) against 5403 N (SD 239.1) for the indirect DCE, p = 0.01334). There was no statistical difference for the displacement measured at 15N and 30N. A direct DCE will result in a postoperative ACJ with greater ultimate failure strength compared to indirect DCE because the inferior ACJ capsule can be better preserved.


In this paper, we propose a new deep image compression framework called Complexity and Bitrate Adaptive Network (CBANet), which aims to learn one single network to support variable bitrate coding under different computational complexity constraints. In contrast to the existing state-of-the-art learning based image compression frameworks that only consider the rate-distortion trade-off without introducing any constraint related to the computational complexity, our CBANet considers the trade-off between the rate and distortion under dynamic computational complexity constraints. Specifically, to decode the images with one single decoder under various computational complexity constraints, we propose a new multi-branch complexity adaptive module, in which each branch only takes a small portion of the computational budget of the decoder. The reconstructed images with different visual qualities can be readily generated by using different numbers of branches. Furthermore, to achieve variable bitrate decoding with one single decoder, we propose a bitrate adaptive module to project the representation from a base bitrate to the expected representation at a target bitrate for transmission. Then it will project the transmitted representation at the target bitrate back to that at the base bitrate for the decoding process. The proposed bit adaptive module can significantly reduce the storage requirement for deployment platforms. As a result, our CBANet enables one single codec to support multiple bitrate decoding under various computational complexity constraints. Comprehensive experiments on two benchmark datasets demonstrate the effectiveness of our CBANet for deep image compression.


Background: C-X-C motif chemokine 17 (CXCL17), a newly identified chemokine, and its possible receptor, G-protein coupled receptor 35 (GPR35) were potential proteins involved in carcinogenesis; nevertheless, their involvement in gastric cancer (GC) initiation and development, which we aimed to evaluated in this study, remains undefined.Methods and materials: CXCL17 and GPR35 expressions in normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissues was determined by immunohistochemistry. Their possible roles were analyzed by the Cancer Genome Atlas (TCGA) data mining and western blot.Results: Either CXCL17 or GPR35 showed a strongest expression in GC-IM among the four types of tissues: CXCL17: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.001); GPR35: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.01). Their expressions were positively correlated in GC tissues (Spearman r = 0.2933, P < 0.001). CXCL17 expression was negatively correlated with the depth of tumor invasion (P = 0.015) and tumor maximum diameter (P = 0.003). Higher CXCL17 expression independently predicted for better survival in GC patients. TCGA analysis suggested CXCL17 expression was positively correlated with the transcriptional level of gastric mucosal maturation indicators TFF1, TFF2, PGC and MUC5AC, but negatively with the dedifferentiation indicators CDX1 and SFRP family members. Protein-protein interaction (PPI) revealed the potential connection of GPR35-CXCL17-CCL20. Overexpressing CXCL17 in HGC27 cell line downregulated SFRP2 and CDX1, but upregulated CCL20 expression.Conclusion: CXCL17 and GPR35 may play a vital role in GC initiation and development, especially in the IM to GC process. A higher CXCL17 expression independently predicted for better survival in GC patients, with a possible role in maintaining gastric mucosa maturation.


A nanoscale composite consisting of 30 vol% magnetic strontium hexaferrite SrFe12O19 embedded in a high dielectric permittivity matrix of BaTiO3 has been produced by the spark plasma sintering method. The morphology and phase composition were characterized by transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) techniques. TEM micrographs indicate that no considerable grain growth occurs and different strained regions were formed by the sintering process. XRD investigations show no evidence of a chemical reaction between the constituents. The dielectric properties of such a nanocomposite were investigated versus temperature (50–300 K), frequency (100 Hz to 100 kHz) and magnetic field (0–5.6 Tesla). A magnetodielectric (MD) effect was detected in the whole studied temperature range. Above 150 K the occurrence of sharp magnetodielectric resonances around 1 kHz leads to a considerable enhancement of the effect. At temperatures below 150 K a positive MD effect was detected which is independent of the frequency.


Simultaneous detection of multiple toxic gases in the air using room temperature gas sensors is significant in low-power environmental monitoring applications. However, the low-temperature resistive gas sensors are sensitive to more than one gas, and thus, an array of gas sensors and high energy-consuming machine learning algorithms are required to predict the concentrations of the individual gases in mixed target gas. Here, we report a computationally less intensive method to predict the composition of the target gases using linear gas sensors. A sensor array consisting of two ZnS resistive gas sensors biased at different voltages in conjunction with the superposition principle is used to predict the concentration of individual gases in the binary mixture of NH3 and CO present in the air. Further, the effect of humidity on response is mitigated by formulating the sensitivity of the sensors as a function of relative humidity. The proposed algorithm predicted the concentration of the individual gases in mixed gas with a maximum absolute error of ∼15% irrespective of humidity levels, which is practically allowed in most gas sensing applications. As the superposition principle is a low-power consuming technique, the proposed approach can be used in applications where trace levels of gases in mixed targets need to be detected with energy-efficient methods.


An autonomous underwater vehicle (AUV) capable of both low speed hovering and high speed flight-style operation is introduced. To have this capability the AUV is over-actuated with a rear propeller, four control surfaces and four through-body tunnel thrusters. In this work the actuators are modelled and the non-linearities and uncertainties are identified and discussed with specific regard to operation at different speeds. A thruster-actuated depth control algorithm and a flight-style control-surface actuated depth controller are presented. These controllers are then coupled using model reference feedback to enable transition between the two controllers to enable vehicle stability throughout the speed range. Results from 3 degrees-of-freedom simulations of the AUV using the new controller are presented, showing that the controller works well to smoothly transition between controllers. The performance of the depth controller appears asymmetric with better performance whilst diving than ascending


Colloidal metal/semiconductor hybrid nanoparticles, containing a Group I-VII semiconductor (AgBr) coupled with a noble metal (Ag), are synthesized in an organic solvent using a single-phase, room-temperature method. Methanol is added to a precursor solution containing silver ions complexed with an alkylammonium bromide surfactant. The methanol appears to cause AgBr precipitation while also acting as a reducing agent for silver ions in solution; the reduced silver clusters grow preferentially onto the AgBr, forming dimer particles that are coated with an alkanethiol to passivate the surface. The structure and composition of the hybrid nanocrystals are studied using TEM and XRD. Surprisingly, despite the relatively broad size distribution of the colloids, the ratio between the diameters of the two domains is approximately constant. This suggests that both portions of the dimer nanocrystal nucleate and grow simultaneously, representing a new type of mechanism for the formation of hybrid nanoparticles.


Mantis species have a variety of different morphologies, so do the extreme forms of mantis limbs trade prey catching capability for camouflage? We hypothesize that some extreme forms of mantis limbs that are associated with cryptic species may be associated with a tradeoff of the capability of those limbs. Previous research has developed 2D morphologies of several hundred species of mantises. We are creating a 3D morphology by using micro dissection, micro CT imaging to construct our 3D biomechanical model. We found the attachment points of the ligaments and muscles from a Tenodera forearm and have constructed a 2D biomechanical model.


We used DNA self-assembly methods to fabricate a series of core-shell gold nanoparticle-DNA-colloidal quantum dot (AuNP-DNA-Qdot) nanoclusters with satellite-like architecture to modulate optical (photoluminescence) response. By varying the intercomponent distance through the DNA linker length designs, we demonstrate precise tuning of the plasmon-exciton interaction and the optical behavior of the nanoclusters from regimes characterized by photoluminescence quenching to photoluminescence enhancement. The combination of detailed X-ray scattering probing with photoluminescence intensity and lifetime studies revealed the relation between the cluster structure and its optical output. Compared to conventional light-harvesting systems like conjugated polymers and multichromophoric dendrimers, the proposed nanoclusters bring enhanced flexibility in controlling the optical behavior toward a desired application, and they can be regarded as controllable optical switches via the optically pumped color.


OBJECTIVES To assess health status, level of social support, and presence of coronary artery disease risk factors before and after coronary artery bypass grafting (CABG); to assess symptomatic relief approximately 12 months postoperatively; and to examine the association between preoperative health status and recurrence of symptoms. DESIGN Observational study. SETTING Preoperatively, in hospital outpatient department (1995–1996); postoperatively, at home (1996–97). SUBJECTS AND METHODS Patients awaiting elective CABG were recruited one month before the expected date of operation. Preoperative assessment included severity of symptoms, coronary artery disease risk factors, short form 36 (SF-36) questionnaire, and social activities questionnaire. The presence and severity of angina and breathlessness were reported postoperatively (mean 16.4 months). Multiple regression analysis was used to identify factors associated with improved outcome following CABG. MAIN OUTCOME MEASURE Patient reported presence and severity of angina and breathlessness. RESULTS 183 patients were followed for a mean of 16.4 months after CABG. Angina and breathlessness were completely relieved in 55% and 36% of patients, respectively. In patients with residual symptoms, the severity was significantly reduced (angina p < 0.001; breathlessness, p = 0.02). Patients with low SF-36 scores and low social network scores preoperatively were less likely to be relieved of symptoms (p < 0.001). Health status and social support levels preoperatively were lower than in other reported coronary artery disease patients groups. Preoperatively, coronary artery disease risk factors were higher than recommended in current guidelines: 67.4% had raised plasma cholesterol, 39.0% were hypertensive, 80% were moderately obese, and 22.9% were smokers. CONCLUSIONS Recurrence of symptoms exceeded other published studies. Patients' perception of general health, symptoms, and social support influences outcome.


Intradural extramedullary location of ependymoma is rare. To the best of our knowledge, only 9 cases have been described in the literature. We report a case of a histologically confirmed ependymoma (WHO grade II) presented in the MR imaging as a cystic, nonenhancing thoracic intradural extramedullary lesion compressing the spinal cord. The cystic appearance mimicking an arachnoid cyst at diagnosis and the leptomeningeal dissemination developed later were peculiarities that have never been previously described in relation to these rare tumors.


The active movement of fluorescence-labeled actin filaments along thick filaments isolated from molluscan smooth muscle was observed. Along a single thick filament, actin filaments moved toward the center of the thick filament at the speed of 1.19 +/- 0.38 microns s-1 (mean +/- SD, n = 42) and detached themselves from it upon reaching the central zone. Movement of actin also occurred in the opposite direction, i.e., away from the center, albeit at a much lower velocity (0.09 +/- 0.07 microns s-1, n = 17). Thus, the thick filament shows functional bipolarity in terms of velocity but does not determine the direction of the movement.


books of this sort, the Annual is happiest dealing with a literary text and is hard put to encapsulize the interesting experimental work carried on by ensembles. What the illustrations best illustrate is the sorry conditions of theatrical photography in the United States. Virtually every picture is a posed publicity shot, often using the traditional composition one large face in the foreground, two smaller figures at the back. The lighting is flat and garish. None of these pictures would answer Muriel St Clare Byrne's criterion, stated in Theatre Notebook many years ago, that a production photograph should accurately reproduce a moment that occurred on stage during a performance. Similarly, the critical obiter dicta, for the most part, tell us less about the play and its production than they do the lack of intellectual credentials of the critics and the shopworn cliches that daily reviewers fall back on. It becomes axiomatic that whatever Richard Eder liked, Clive Barnes did not, and vice-versa, John Simon's self-consciously snide wise-cracks are at least fun to read, however outrageous they must be for actors to endure. But, by and large, we get samples of ignorance, such as Walter Kerr chiding the director of The Inspector General for including a gag that appears in Gogol's own stage directions, or of grotesque puffery, overstrained in its reaching for superlatives, such as Douglas Watts' judgement of Bedroom Farce: 'A masterly comic construction, inventive enough to make Feydeau's cheeks burn in his grave.' The image is not one to dwell upon.


In 2015, more than one million migrants and refugees arrived in Europe. Commercial complementary foods, processed foods marketed for infants and young children 6-23 months of age, were distributed by various humanitarian actors along migrant routes and in European refugee camps. Unsolicited donations and distributions of commercial complementary food products were problematic and divergent from international policies on infant and young child feeding during humanitarian emergencies. Interim guidance regarding commercial complementary foods was published during the peak of the emergency but implemented differently by various humanitarian actors. Clearer and more technical specifications on commercial complementary foods are needed in order to objectively determine their suitability for operational contexts in Europe and emergency nutrition assistance in the future.


Load balancing is a common approach for task
assignment in distributed architectures. In this paper, we show
that the degree of inefficiency in load balancing designs is highly
dependent on the scheduling discipline used at each of the backend
servers. Traditionally, the back-end scheduler can be modeled
as Processor Sharing (PS), in which case the degree of inefficiency
grows linearly with the number of servers. However, if the back-end
scheduler is changed to Shortest Remaining Processing Time
(SRPT), the degree of inefficiency can be independent of the
number of servers, instead depending only on the heterogeneity
of the speeds of the servers. Further, switching the back-end
scheduler to SRPT can provide significant improvements in
the overall mean response time of the system as long as the
heterogeneity of the server speeds is small.


Globally a lot of changes have been taken place in the last hundred years with men accepting women working outside of their homes because of the dire economic needs of the family, society and sometimes the countries also. Women in this era work at odd hours, especially working all night side by side with men. With all the advancements in technology and attitudes there are still societies in which women are not able to achieve their full potential as many domestic factors stand as barriers in a woman's professional life. One of the major problems is handling the different roles they play at their work place and at home. Due to these conflicting expectations women are facing difficulties and they are put to a lot of stress that affects their physical and mental health. In this paper we will examine the common problems faced by working women globally.


Gallium-prostate-specific membrane antigen (Ga-PSMA) is well established in the imaging of prostate cancer (PC). Here, we report a case of castration-resistant PC who underwent Ga-PSMA PET/CT for recurrence evaluation, which revealed metastatic lesions in distant lymph nodes and additionally an unusual metastatic deposit in the inguinal canal. The second Ga-PSMA PET/CT done after oral hormonal therapy yielded a favorable response. This pattern of distant metastatic spread is a rare presentation of PC, and PSMA PET/CT revealed the unusual metastasis in the inguinal canal with a timely therapy culminating in favorable disease response.


Mineral compositions have long been used as indicators of the provenance and tectonic setting of source rocks for sandstones and shales. Extraction of the same information from limestones is less common because of the general paucity of the non-carbonate phase and the greater processing time that is required to concentrate the frequently encountered small quantities of detrital (and authigenic) minerals. The insoluble component, however, contains a great deal of valuable information and should not be ignored. The clays and other insoluble minerals in limestones from southeastern United States and the Caribbean region, for example, clearly reflect the volcanic activity that was associated with formation of the Mid-Atlantic Ridge rift system and the opening of the Atlantic Ocean and Gulf of Mexico. Similarly, major periods of orogeny during the Paleozoic and Mesozoic have left their signature, even in carbonate rocks that originated far from the sites where uplift was taking place. In other cases, the insoluble residue component clearly manifests periods of quiescence in adjacent land areas or testifies to the airborne transport of insoluble components from sources as far distant as the Saharan Desert of Africa. Similarly, insoluble components have convincingly shown that the origin of the extensive bauxite deposits more » found in Jamaican limestones are the result of alteration of interbedded volcanic ash units and have not resulted from accumulation of the detritus in the limestones. Residue analysis in Gulf Coast limestones can be successfully used for subsurface identification and correlation of carbonate units in the exploration for hydrocarbons, to reconstruct sedimentary environments, to identify missing sections, and to identify paraconformable realtionships between adjacent carbonate units that are otherwise similar in appearance. The latter is especially useful where extensive recrystallization has taken place and fossils have been destroyed. « less


Information filtering systems have traditionally relied on some form of content analysis of documents to represent a profile of user interests. Such content-based filtering is generally ineffective in domains with diverse media types such as audio, video, and images, because machine-analysis of such media is hard. Recently, information filtering systems relying primarily on human evaluations of documents have been built. Such automated collaborative filtering (ACF) systems work by discovering correlations in evaluations of documents amongst users, and by using these correlations to recommend new documents. However, such systems rely on the implicit assumption that the domain can be partitioned in some logical way (such as all articles in a particular newsgroup), prior to applying the ACF algorithm. This assumption breaks down in broad domains, (such as all documents in the World Wide Web), where no natural partition of the document space exists. This thesis claims that content-based and automated collaborative filtering are complementary techniques, and the combination of ACF with some easily extractable features of documents is a powerful information filtering technique for complex information spaces. Furthermore, systems using such feature guided automated collaborative filtering (FGACF) techniques can provide users with a very powerful information retrieval metaphor personalized querying by example. WEBHOUND, an FGACF based system for personalized World Wide Web document recommendations was built to demonstrate the technique and test its effectiveness. Thesis Supervisor: Pattie Maes Title: Associate Professor of Media Arts and Sciences This work was supported in part by a grant from the News In The Future consortium and a fellowship from the Motorola Corporation Feature Guided Automated Collaborative Filtering Yezdezard Zerxes Lashkari The following people served as readersfor this thesis: Reader Mitchell Kapor Adjunct Professor Program in Media Arts and Sciences Co-Founder, Electronic Frontier Foundation Reader Tim Berners-Lee Director, World Wide Web Consortium Research Scientist, MIT Laboratory for Computer Science Reader el Hawley Assistant Professor of Media and Sciences Program in Media Arts and Sciences Director, Personal Information Architecture Group, MITMedia Laboratory


Links to databses and guidance on how to do research. See below for recent publications in speech pathology. See the rest of this guide for help with doing your own research.


Introduction: CAR T-cell therapy (CART) has dramatically improved outcomes for patients (pts) with relapsed/refractory (r/r) DLBCL, but the majority of pts still have poor outcomes due to progressive disease and toxicities. Here we used a machine learning algorithm to rank the prognostic impact of specific comorbidities measured by the Cumulative Illness Rating Scale (CIRS) in DLBCL pts indicated for CART in a multicenter learning cohort (LC) and a separate validation cohort (VC). Methods: pts with r/r DLBCL included in RWE analysis underwent leukapheresis for CART at 10 academic centers. CIRS was assessed at the time of T-cell collection (Salvi et al, 2008). Progression-free survival (PFS) and overall survival (OS) were measured from T-cell collection. Random survival forest (RSF) modeling of PFS and OS was repeatedly applied to random subsets of the LC to determine the most important CIRS categories and comorbidity levels in the presence of known prognostic factors. Cox proportional hazards models of PFS and OS were fit to both cohorts. Associations between comorbidities and CART adverse events were evaluated with Fisher's exact test. Results: The LC comprised 577 pts, median age of 63 (range, 19-90); 90% had ECOG 0-1. Median number of prior therapies was 3 (range, 1-11). GCB subtype was found in 54% of pts, with 38% non-GCB and 8% unknown. Twenty-seven pts (4.7%) died before CART infusion. Of the 550 pts who received CART, 71% got axicabtagene ciloleucel, 22% tisagenlecleucel, and 7% lisocabtagene maraleucel. The median CIRS score was 7 (range, 0-25) with 54% having CIRS ≥7. The median PFS was 11 months (95% CI: 8 – 15) and OS 30 months (95% CI: 23 – NA), with a median follow-up time of 20 months. Although CIRS ≥7 was significantly associated with PFS (HR=1.26) and OS (HR=1.35) in univariable analysis, it did not remain significant in multivariable models. According to a RSF tree depth-weighted nodal split score, severe comorbidities in the following CIRS categories had the greatest impact on PFS: respiratory, upper GI, renal, and hepatic (denoted Severe4, 9% of pts). When accounting for other significant variables, Severe4 was independently associated with inferior PFS (HR=2.45, p<0.001) and OS (HR=2.30, p<0.001) in the LC. This finding was recapitulated in a single-center VC (n=218, median follow-up of 35 months, median age 61 years, median of 3 prior therapies, ECOG 0-1 in 74%, Severe4 in 16% of pts, 98% receiving axicabtagene ciloleucel) as Severe4 remained independently associated with inferior PFS (HR=1.84, p=0.003) and OS (HR=1.82, p=0.007). Pts with Severe4 also had a higher rate of grade ≥3 CRS (16% vs 6%; p=0.013), while development of grade ≥3 ICANS was associated with CIRS ≥7 (26% vs 12%; p<0.001).Conclusions: In this large RWE study, we identify and validate a composite index comprising four organ systems (respiratory, upper GI, renal and hepatic; Severe4) that correlates with survival outcomes in CART recipients for r/r DLBCL. GS & AK contributed equally
 Citation Format: Geoffrey Shouse, Andy Kaempf, Max Gordon, David Yashar, Audrey M Sigmund, Gordon Smilnak, Steven M Bair, Agrima Mian, Lindsey Fitzgerald, Amneet Bajwa, Samantha Jaglowski, Neil Bailey, Mayzar Shadman, Krish Patel, Deborah M Stephens, Manali Kamdar, Brian T Hill, Jordon Gauthier, Reem Karmali, Loretta Nastoupil, Adam S Kittai, Alexey V Danilov. Impact of a validated composite comorbidity score on outcomes in patients treated with CAR T-cell therapy for diffuse large B cell lymphoma (DLBCL): A multicenter real-world evidence (RWE) study [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr A27.


Ochratoxin A is a nephrotoxic and tumorigenic mycotoxin which contaminates a variety of food items, resulting in chronic human exposure. Biotransformation reactions have been implicated in the tumorigenicity of ochratoxin A. The biotransformation of ochratoxin A by cytochromes P450 and other mammalian enzymes was investigated to optimize conditions for bacterial mutagenicity testing. Metabolite formation was assessed by HPLC with UV and fluorescence detection and by LC/MS/MS. When ochratoxin A was incubated with liver microsomes from rats and mice, formation of 4R- and 4S-hydroxyochratoxin A was observed at very low rates. However, oxidation of ochratoxin A was not observed using kidney microsomes from rats and mice. Significantly higher rates of oxidation were seen in liver microsomes from rats pretreated with 3-methylcholanthrene and dexamethasone. Other reported or postulated that ochratoxin A-metabolites were not formed in detectable concentrations. Human cytochromes P450 (3A4, 1A2, and 2C9-1 Supersomes((R))) also showed very low activity with ochratoxin A (<60 fmole/min x pmol P450). Other enzyme systems used to study possible biotransformation of ochratoxin A were rat and human liver and kidney S-9 fortified with NADPH and glutathione, semipurified glutathione S-transferases, horseradish peroxidase, and soybean lipoxygenase; none of these resulted in detectable biotransformation of ochratoxin A. Using rat liver microsomes with high activity for ochratoxin A oxidation and the other enzyme systems to activate ochratoxin A for mutagenicity testing in the Ames test, mutagenicity was not observed in Salmonella typhimurium TA 100 and TA 2638. The obtained results suggest that oxidative biotransformation of ochratoxin A occurs at low rates, is catalyzed by cytochromes P450, and is unlikely to form reactive intermediates capable of binding to DNA.


BACKGROUND
Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score (hypertension, age ≥ 75 years, transient ischemic attack or stroke [2 points], COPD, and heart failure [2 points]) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism.

METHODS
The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years.

RESULTS
Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P < .01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 (P < .001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P < .05). Baseline CHADS(2) (congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69).

CONCLUSIONS
This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly influenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events.


Thin-film-based solid oxide fuel cells with reduced electrolyte thickness have been developed in an effort to lower the operating temperatures and increase the cost competitiveness and lifetime of the devices. Although silver has gained a considerable amount of attention as a cathode material with excellent oxygen reduction activity at lower temperatures, thermal instability due to agglomeration is a major disadvantage associated with the use of silver. Many oxide coating methods have been suggested to overcome this problem, but the results remain unsatisfactory. Here, we propose cathodic electrochemical deposition (CELD) as a new strategy to improve the activity and stability of silver electrodes. Pr-doped ceria is coated onto a nanoporous silver film by CELD and analyzed by electron microscopy, mass spectrometry, and X-ray diffraction. AC impedance spectroscopy of symmetric cells (electrode|electrolyte|electrode) reveals that only a few minutes of CELD increases the electrode activity by approximately 33 times and achieves outstanding durability with no degradation, even at 550 °C for 50 hours. Electrolyte-supported single cells are also fabricated to demonstrate the enhanced performance of the Ag electrode created via the ceria overcoats.


In addition to the self-interference due to multipath, the presence of multiple access interference further degrades the performance of CDMA systems. In the analysis of multipath combining receivers, Turin (1980) used Gaussian approximations to account for the effect of multiple access interference. The aim of the paper is to show on a simulation basis, the BER performance of a DS CDMA system operating in multipath fading mobile radio environment with up to two interfering signals. A 2-ray model of equal amplitude and 1.0 mu s excess delay, and a 6-ray model with multipath profiles for typical urban, rural area and hilly terrain as specified for the GSM system have been employed.


Thermodynamic stabilities of ylides are measured by the ease of the carbanion formation through the removal of a proton from their precursors. A full-spectrum scale of ylide thermodynamic stability is important to understand the reactivities and selectivities in ylide chemistry. In the present study is reported the first theoretical protocol for predicting the acidities of structurally unrelated ylide precursors in DMSO whose reliability has been tested against almost all the available experimental data. The ONIOM/G3B3//HF//CPCM/Bondi method is found to be the optimal protocol to handle the N-, P-, and S-containing ylides, whereas the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d)//HF//CPCM/Bondi method can be used to deal with those systems for which the ONIOM/G3B3 method is not feasible. Extensive calculations on about 80 experimentally characterized ylide precursors show that this theoretical protocol can reliably predict the pK(a) values of diverse structurally unrelated ylide precursors in DMSO with an error bar of ca. 1.6-1.9 pK(a) units. With the authorized theoretical protocol in hand, we have developed an extensive scale of ylide thermodynamic stability that may find applications in synthetic organic chemistry.


Neuromedin U (NmU) is a smooth muscle contracting peptide. Recently, two G-protein-coupled receptors for NmU (NmU1R and NmU2R) have been cloned having approximately 50% homology. They have distinct patterns of expression suggesting they may have different biological functions. This study provides a comprehensive characterization of both NmU receptors expressed in human embryonic kidney 293 cells. [125I]hNmU binding to the recombinant NmU receptors was rapid, saturable, of high affinity and to a single population of binding sites. Exposure of these cells to NmU isopeptides resulted in an increase in intracellular [Ca2+]i release (EC50 value of 0.50 ± 0.10 nmol/l) and inositol phosphate formation (EC50 1.6 ± 0.2 and 1.50 ± 0.4 nmol/l for NmU1R and NmU2R respectively). Furthermore, hNmU inhibited forskolin (3 µmol/l)-stimulated accumulation of cAMP in intact HEK-293 cells expressing either NmU1R or NmU2R. The inhibitory effect was significant for the cells expressing NmU2R with IC50 value of 0.80 ± 0.21 nmol/l. In summary, both NmU1R and NmU2R in HEK-293 cells have similar signaling capability.