This paper presents the discrete-time LQG/LTR design of a disk drive track following servo system. The servo compensator designed through linear-quadratic Gaussian control combined with loop transfer recovery (LQG/LTR) consists of a Kalman filter for state estimation and state feedback for control. The desired tracking servo performance is first formulated through a frequency shaped return ratio of the Kalman filter and subsequently recovered at the output of the plant/compensator loop through the automatic design of a discrete-time linear quadratic (LQ) regulator. Particular attention has been given to modeling the calculation time delay and bias force estimation. The excellent robustness and performance characteristics of a continuous time LQG/LTR design are theoretically unachievable due to the extremely low sampling rate and nonminimum phase plant characteristics. However, both time and frequency domain simulations show that reasonable stability margins and performance can still be recovered. This technique nearly eliminates all the trial and error typical of a conventional pole placement design of a similar system. The direct discrete-time design can handle extremely low sampling rates associated with embedded servo systems. The technique can also be used for designing multi-rate and multi-input servo systems. >


100-150 words) Software is usually studied in terms of the changes triggered by its operations in the material world. Yet, to understand its social and cultural impact, one needs to examine also the different narratives that circulate about it. Software's opacity, in fact, makes it prone to being translated into a plurality of narratives that help people make sense of its functioning and presence. Drawing from the case of Joseph Weizenbaum's ELIZA, widely considered the first chatbot ever created, this paper proposes a theoretical framework based on the concept of "biographies of media" to illuminate the dynamics and implications of software's discursive life. The case of ELIZA is particularly relevant in this regard because it became the center of competing narratives, whose trajectories transcended the actual functioning of this program and shaped key controversies about the implications of computing and AI.


Background The appropriate management of patients with ST-segment elevation myocardial infarction (STEMI) depends on accurate interpretation of the 12-lead ECG by paramedics. Computer interpretation messages on ECGs are often provided, but the effect they exert on paramedics' decision-making is not known. The objective of this study was to assess the feasibility of using an online assessment tool, and collect pilot data, for a definitive trial to determine the effect of computer interpretation messages on paramedics' diagnosis of STEMI. Methods The Recognition of STEMI by Paramedics and the Effect of Computer inTerpretation (RESPECT) feasibility study was a randomised crossover trial using a bespoke, web-based assessment tool. Participants were randomly allocated 12 of 48 ECGs, with an equal mix of correct and incorrect computer interpretation messages, and STEMI and STEMI-mimics. The nature of the responses required a cross-classified multi-level model. Results 254 paramedics consented into the study, 205 completing the first phase and 150 completing phase two. The adjusted OR for a correct paramedic interpretation, when the computer interpretation was correct (true positive for STEMI or true negative for STEMI-mimic), was 1.80 (95% CI 0.84 to 4.91) and 0.58 (95% CI 0.41 to 0.81) when the computer interpretation was incorrect (false positive for STEMI or false negative for STEMI-mimic). The intraclass correlation coefficient for correct computer interpretations was 0.33 for participants and 0.17 for ECGs, and for incorrect computer interpretations, 0.06 for participants and 0.01 for ECGs. Conclusions Determining the effect of computer interpretation messages using a web-based assessment tool is feasible, but the design needs to take clustered data into account. Pilot data suggest that computer messages influence paramedic interpretation, improving accuracy when correct and worsening accuracy when incorrect.


Quality has become a fundamental requirement for success and sustainability of websites. This study discusses the evaluation of some e-Learning websites as one of the main sources of information to administrators, students and teachers in the educational systems. This article investigates the quality of e-learning websites in the Middle East in term of usability and content accessibility. Eleven websites from eleven countries were selected for this study. Evaluations process is done based on different web diagnostic tools and measures. The experimental results show several issues on usability and content accessibility of the selected e-learning websites. Many usability problems with respect of speed and number of broken links were found. Moreover, the design of the selected websites is not fit with the content accessibility standards.


The idea of the asynchronous transmission in wavelength division multiplexing (WDM) ring MANs is studied in this paper. Especially, we present an efficient access technique to coordinate the collisions-free transmission of the variable sizes of IP traffic in WDM ring core networks. Each node is equipped with a tunable transmitter and a tunable receiver. In this way, all the wavelengths are exploited for both transmission and reception. In order to evaluate the performance measures of average throughput, queuing delay and packet dropping probability at the buffers, a simulation model that assumes symmetric access rights among the nodes is developed based on Poisson statistics. Extensive numerical results show that the proposed protocol achieves apart from high bandwidth exploitation for a wide range of offered load, fairness of queuing delay and dropping events among the different packets size categories. Keywords—Asynchronous transmission, collision avoidance, wavelength division multiplexing.


Health leaders and scientists worldwide consider antibiotic resistance among the world's most dangerous pathogens as one of the biggest threats to global health. Antibiotic resistance has largely been attributed to genetic changes, but the role and recalcitrance of biofilms, largely due to growth state dependent adaptive resistance, is becoming increasingly appreciated. Biofilms are mono- and multi-species microbial communities embedded in an extracellular, protective matrix. In this growth state, bacteria are transcriptionally primed to survive extracellular stresses. Adaptations, affecting metabolism, regulation, surface charge, immune recognition and clearance, allow bacteria to thrive in the human body and withstand antibiotics and the host immune system. Biofilms resist clearance by multiple antibiotics and have a major role in chronic infections, causing more than 65% of all infections. No specific antibiofilm agents have been developed. Thus, there is a pressing need for alternatives to traditional antibiotics that directly inhibit and/or eradicate biofilms. Host defence peptides (HDPs) are small cationic peptides that are part of the innate immune system to both directly kill microbes but also function to modulate the immune response. Specific HDPs and their derivatives demonstrate broad-spectrum activity against biofilms. In vivo biofilm assays show efficacy in abscess, respiratory, in-dwelling device, contact lens and skin infection models. Further progress has been made through the study of ex vivo organoid and air–liquid interface models to better understand human infections and treatment while relieving the burden and complex nature of animal models. These avenues pave the way for a better understanding and treatment of the underlying cause of chronic infections that challenge the healthcare system.


Abstract Immigrant associations in Germany are increasingly approached as experts and included in administrative action. This article develops a heuristic informed by governmentality studies to analyse this cooperation practice. A document analysis shows that immigrant associations are addressed as "bridge builders" between public administration and migrants. Interviews with actors in a municipal cooperation setting in Berlin reveal the paradoxes of this interpellation as well as reflexive strategies of organisational self-positioning.


Advanced vaccine research approaches need to explore on biodegradable nanoparticles (NPs) based vaccine carrier that can serve as antigen delivery systems as well as immuno-stimulatory action to induce both innate and adaptive immune response. The biodegradable polymeric particles like polylactide-co-glycolide (PLGA) or polylactide (PLA), not only work as a delivery system but also, provide adjuvant activity and marks in the development of long -lasting immunity. In this PhD dissertation work, the immunogenicity of PLA and PLGA NPs encapsulating outer membrane protein (Omp) antigen (Aeromonas hydrophila and Vibrio cholerae) were evaluated. Initially, Various NPs formulations of PLA and PLGA loaded with model protein (Bovine Serum Albumin) or drug (Clindamycin hydrochloride) were prepared by solvent evaporation method varying drug/protein: polymer concentration and optimized for size, encapsulation efficiency, drug loading, morphology etc. A. hydrophila Omp antigen loaded PLA-Omp (223.5± 13.19 nm) and PLGA-Omp (166.4± 21.23 nm) NPs were prepared using double emulsion method by efficiently encapsulating the antigen reaching the encapsulation efficiency 44 ± 4.58 % and 59.33± 5.13 % respectively. Despite low antigen loading in PLA-Omp, it exhibited considerably slower antigen release in vitro than PLGA-Omp NPs. Upon intraperitoneal immunization in fish, Labeo rohita with all antigenic formulations (PLA-Omp NP, PLGA-Omp NP, FIA-Omp, PLA NP, PLGA NP, PBS as control), significantly higher bacterial agglutination titre and haemolytic activity were observed in the case of PLA-Omp and PLGA-Omp immunized groups compared to rest of the groups at both 21 days and 42 days.The antigen specific antibody response was significantly increased and persisted up to 42 days of post immunization by PLA-Omp, PLGA-Omp, FIA-Omp.PLA-Omp NPs showed a better immune response (higher bacterial agglutination titre, haemolytic activity, specific antibody titre, higher percent survival upon A. hydrophila challenge) than PLGA-Omp in L. rohita confirming its better efficacy. Comparable antibody response of PLA-Omp and PLGA-Omp with FIA-Omp treated groups suggested that PLA and PLGA could be a replacement for Freund's adjuvant (for stimulating antibody response) to overcome many side effects offering long lasting immunity. Similarly, V. cholerae Omp antigen loaded PLA-Omp (196.24± 34.25 nm) and PLGA-Omp (165.34± 3.5 nm) NPs were prepared using double emulsion method by efficiently encapsulating the antigen reaching the encapsulation efficiency 57.85 ± 4.15 % and 69.18± 1.68 respectively. After intraperitoneal immunization in BALB/c mice, the type and strength of immune responses elicited (cellular and humoral) by formulated NPs were evaluated. The antibody titre (IgG1, IgG2a) were significantly higher (P<0.05; Kruskal-Wallis test and post hoc Dunn multiple comparisons) in PLA-Omp NPs, PLGA-Omp NPs treated groups than respective PLA and PLGA NPs treated groups from 7 days to 56 days as confirmed by ELISA tests. Also, PLA-Omp NPs and PLGA-Omp NPs induced significantly higher (P<0.05; Kruskal-Wallis test and post hoc Dunn multiple comparisons) antigen specific IgG titers than Omp antigen treated groups at all-time intervals except 0 day. From the spleen cell analysis (Cell surface phenotype through FACs study), a viii significantly higher cellular activation was observed in the case of PLA-Omp and PLGA-Omp NPs in comparison to Omp antigen alone. Enhanced immune responses elicited by PLA-Omp and PLGA-Omp NPs might be attributed to strong memory T cell response (higher effector memory T cell), efficient induction of dendritic cell (DC) activation (higher MHC I, MHC II, CD 86 expression) and follicular helper T cell differentiation in spleen favoring the generation of antibody responses. Another study aimed at developing a DNA vaccine as well as a delivery system to boost antigenic outer membrane protein (Omp) that would act as potential vaccine candidate was conducted. NPs based delivery systems for plasmid DNA (pDNA) (which encode conserved Omp) administration might be keys to improve the transfection efficiency in vivo even at a lower dose. The conserved antigenic protein sequences [omp(211-382), omp(211-382)opt, omp(703-999) and omp(703-999)opt] of outer membrane protein were identified using bioinformatics tools. The sequences were cloned into a pVAX-GFP expression vector and successfully transformed into E. coli (DH5α). The large scale pDNA production was achieved with shake flask cultures and the pDNA was purified by hydrophobic interaction chromatography (HIC). The formulated PLGA-chitosan NP/plasmid DNA nano complex of ~200 nm (199.25 ± 22.29 nm and 205.25 ±33.59) was transfected in the into CHO cells that confirmed improved transfection efficiency (fluorescence intensity measurement corresponding to GFP expression level from the FACs study) at a lower dose. The DNA entrapment assay demonstrated the possible protection of pDNA inside the pDNA-NP complex. The protection from enzymatic digestion that NP complex confers to pDNA was evaluated and confirmed by gel electrophoresis after treatment with DNase. Further, physio-chemical characterizations of formulated nano complex and extensive transfection studies have proved the functionality of the system in vitro. Overall, the successful formulations of NP based antigen delivery system with all desirable physiochemical characteristics were obtained under highly controlled conditions and reproducibility. The immunological evaluation studies suggest that PLA/PLGA NPs based delivery system could be a novel antigen carrier for fish and mice ensuring its application for commercial value and product development. Further work based on present optimized results can be taken forward for next level vaccine design and approval.


Bilingual tasks, such as bilingual lexicon induction and cross-lingual classification, are crucial for overcoming data sparsity in the target language. Resources required for such tasks are often out-of-domain, thus domain adaptation is an important problem here. We make two contributions. First, we test a delightfully simple method for domain adaptation of bilingual word embeddings. We evaluate these embeddings on two bilingual tasks involving different domains: cross-lingual twitter sentiment classification and medical bilingual lexicon induction. Second, we tailor a broadly applicable semi-supervised classification method from computer vision to these tasks. We show that this method also helps in low-resource setups. Using both methods together we achieve large improvements over our baselines, by using only additional unlabeled data.


Giardia sp infection was believed responsible for chronic, intermittent diarrhea in a group of 14 Persian cats. Seven of the cats were shedding Giardia sp cysts, and 6 of these cats had diarrhea at the time of fecal examination. Conversely, only 1 of 6 clinically normal cats in the group was shedding Giardia sp cysts. Cysts were not detected in feces of 2 cats with diarrhea. Cats less than or equal to 3 years old were more likely to be found shedding cysts. The parasite apparently was eradicated from the cattery by a combination of cage disinfection (1% sodium hypochlorite solution) and oral furazolidone treatment (4 mg/kg of body weight, BID for 5 consecutive days). During treatment, clinical signs resolved, and all cats remained clinically normal 2 months after treatment.


Critic Clive Barnes once called Eugene O'Neill the "world's worst great playwright" and Brooks Atkinson called him "a tragic dramatist with a great knack for old-fashioned melodrama." These descriptions of the man can also be used to describe his work. Despite the fact that O'Neill is the only American playwright to win the Nobel Prize for Literature and his last works are some of America's finest, most of his published works are not good. This work closely examines how O'Neill's failures as a playwright are inspiring and how his disappointments are reflections of his own theory that tragedy requires failure, a theory that is evident in his work. Conflicts in O'Neill's plays are studied at the structural level, with attention paid to genre, language or dialogue, characters, space and time elements, and action. Included is information about O'Neill's life and a chronological listing of all of his 50 plays with basic details such as production history, principal characters, dramatic action, and a brief commentary.


: Fulminant liver failure is characterized by massive acute Hepatocyte dysfunction associated with severe coagulopathy, acute hyperdynamic circulatory failure and hepatic encephalopathy. According to the more recent classification, which takes into account the interval between the onset of jaundice and the hepatic encephalopathy, three are the main forms of ALF hyperacute, acute or subacute. Despite recent and relevant advances in intensive care management and organ support techniques (both artificial and bioartificial), mortality remains extremely high, early deaths being related to cerebral oedema and circulatory failure, whereas late deaths are associated with sepsis and multiple organ failure. Orthotopic liver transplantation has proven to be the only treatment modality able to change radically the ALF natural course. he experiences with artificial and bioartificial devices, in spite of being interesting and sometimes very promising, are far from giving a real impact on survival and remain, so far, important interim measures for patients eventually candidate to liver transplantation.


Violaxanthin de-epoxidase and zeaxanthin epoxidase catalyze the addition and removal of epoxide groups in carotenoids of the xanthophyll cycle in plants. The xanthophyll cycle is implicated in protecting the photosynthetic apparatus from excessive light. Two new sequences for violaxanthin de-epoxidase from tobacco andArabidopsis are described. Although the mature proteins are well conserved, the transit peptides of these proteins are divergent, in contrast to transit peptides from other proteins targeted to the thylakoid lumen. Sequence analyses of both violaxanthin de-epoxidase and zeaxanthin epoxidase establish the xanthophyll cycle enzymes as members of the lipocalin family of proteins. The lipocalin family is a diverse group of proteins that bind small hydrophobic (lipophilic) molecules and share a conserved tertiary structure of eight β-strands forming a barrel configuration. This is the first reported identification of lipocalin proteins in plants.


For estimation the value of the firm, there can be used three approaches: the approach based on assets, the approach based on incomes and the approach based on comparison. Each type of approach include more methods and techniques of evaluation and, in practice can be used all three approaches in order to estimate the value of the firm. Among the patrimonial methods (evaluation based on assets) the most representative are the followings: Net Accounting Asset (ANC); Net Corrected Accounting Asset (ANCc); Net Liquidation Asset (ANL); the substantial value; the permanent capital necessary for exploitation. A comparative analysis of the methods ANC and ANCc reveals the main advantages and disadvantages of them. But the selection of a certain approach or methods depends on the type of firm, on its situation at the evaluation date, on the available information, on the purpose of evaluation etc. and the option for a method or another is based finally on the evaluator's choice which select the used methods in function of the specific conditions where the evaluation is done and of the existing advantages/disadvantages.


Tennessee Williams has been regarded as the greatest Southern dramatist and one of the most distinguished playwrights in the history of American drama. He is undoubtedly the most renowned American dramatist of the second half of the 20th Century. This paper addresses and explores some of the main features of his dramatic works. His drama was a lyric or poetic one, and that is why the critic and scholar Frank Durham referred to him as "Tennessee Williams, theater poet in prose". When David Mamet describes William's plays as "the greatest dramatic poetry in the American language", he shares the widely accepted opinion that Williams brought to the language of the American theater a lyricism unequaled before or after. He infuses his dialogue with lyrical qualities so subtle that the reader or hearer, unaware, responds not to realistic speech but, instead, to speech heightened by such poetic effects as alliteration, rhythm, onomatopoeia, and assonance. As a Southern writer, Williams was attuned to the natural rhythm and melody of Southern speech, a melody, he says, heard especially in the voices of women. Characterization is one of Williams's strongest achievements as a dramatist. His people are imaginatively conceived yet so convincing that it is tempting to take them out of context and theorize about their lives before and after the action of the play. In place of realism, which stressed photographic duplication of the actual, a style that had dominated American stage for four decades, Williams insisted on a theater that was "plastic" that combined all the elements of production- dialogue, action, setting, lighting, even properties- in a unified, symbolic expression of a truth.


Radar-based precipitation nowcasting refers to predicting rain for a short period of time using radar reflectivity images. For dynamic nowcasting, motion fields can be extrapolated using an approximate and localized reduced-order model. Motion field estimation based on traditional Horn-Schunck (HS) algorithm suffers from over-smoothing at discontinuities in nonrigid and dissolving texture present in precipitation nowcasting products. An attempt to preserve the discontinuities using an L1 norm formulation in HS led to the use of Total Variation L1 norm (TVL1). In this paper, we propose a radar-based precipitation nowcasting model with TVL1-based estimation of motion field and Sparse Identification of Non-linear Dynamics (SINDy)-based estimation of non-linear dynamics. TVL1 is effective in preserving the edges especially in the case of the eye of typhoons and squall lines while estimating motion vectors. SINDy captures the nonlinear dynamics and generates the subsequent update values for the motion field based on a reduced-order representation. Finally, the SINDy-generated ensemble of motion field is used along with the radar reflectivity image for generating precipitation nowcasts. We evaluated the effectiveness of TVL1 in preserving edges while capturing the motion field from non-rigid surfaces. The performance of the proposed TVL1-SINDy model in nowcasting weather events such as Typhoons and Squall lines are evaluated using performance metrics such as Mean Absolute Error (MAE), and Critical Success Index (CSI). Experimental results show that the proposed nowcasting system demonstrates better performance compared to the benchmark nowcasting models with lower MAE, higher CSI at higher lead times.


In a sequential auction with multiple bidding agents, it is highly challenging to determine the ordering of the items to sell in order to maximize the revenue due to the fact that the autonomy and private information of the agents heavily influence the outcome of the auction. The main contribution of this paper is two-fold. First, we demonstrate how to apply machine learning techniques to solve the optimal ordering problem in sequential auctions. We learn regression models from historical auctions, which are subsequently used to predict the expected value of orderings for new auctions. Given the learned models, we propose two types of optimization methods: a blackbox best-first search approach, and a novel white-box approach that maps learned models to integer linear programs (ILP) which can then be solved by any ILPsolver. Although the studied auction design problem is hard, our proposed optimization methods obtain good orderings with high revenues. Our second main contribution is the insight that the internal structure of regression models can be efficiently evaluated inside an ILP solver for optimization purposes. To this end, we provide efficient encodings of regression trees and linear regression models as ILP constraints. This new way of using learned models for optimization is promising. As the experimental results show, it significantly outperforms the black-box best-first search in nearly all settings.


Amyloidosis is an inherited or acquired systemic storage disease in which a pathologic, amorphous substance produced as a result of abnormal protein metabolism and resistant to proteolysis is deposited in the extracellular space of various tissues (intracellular deposits occur rarely). This leads to the destruction of normal tissue architecture and disturbs its function. The development of amyloidosis is associated with the transformation of the α-spiral conformation of fibrous protein into a stratified, parallel, folded spatial β-conformation. The transition of the fibrous proteins conformation and their tissue localization causes resistance of the fibers to proteolytic processes as a result of a limited access of the protein converting enzymes. In this paper we show the actual classification of amyloidosis and up-to-date knowledge about the amyloid structure, development and etiopathogenesis of AL amyloidosis (Adv Clin Exp Med 2011, 20, 5, 647–652).


Approaches to nurses' safety in health care organizations, including modifying individual behavior through enforced compliance with safety rules and mandatory participation in safety training, have been of only modest benefit in reducing injuries. Apparently, what matters is not the existence of guidelines, but their implementation. The aim of the present study was to explore nurses' implicit safety theories concerning when to comply with safety rules. Using a multimethod approach, including semistructured interviews (perceptions), observations (real-time behavior), and documentary evidence from 15 nursing units (90 nurses), we found that nurses developed implicit rules for when and how to protect themselves. These included: (a) continue providing care for the patient even at the price of protecting yourself, (b) do not disturb other nurses' work, (c) it cannot happen to me!, (d) be aware of recently occurring accidents, and (e) protect yourself when significant others are present. These implicit rules seemed to be reinforced by personal, social, and contextual factors at the unit, limiting the likelihood that the decision makers (nurses) would discover their fallacy.


The U.S. Department of Justice and the Federal Trade Commission are currently in the process of revising their Horizontal Merger Guidelines. I explain that if a revision is to occur, then there are certain parts of the Guidelines that are most in need of revision, including the sections on unilateral and coordinated effects, committed and uncommitted entry, numerical concentration thresholds for safe harbors, and fixed costs. I also explain what should not become part of any new Guidelines, such as replacing the market definition/market concentration starting point with a competitive effects framework such as "upward pricing pressure." The proposed Guidelines were published in April 2010. I present my reactions to the proposed Guidelines and discuss several caveats that courts, foreign antitrust agencies, and the business community should be aware of as they try to interpret what the proposed Guidelines suggest about appropriate antitrust policy.


The authors related two cases of multiple myeloma BJX and GX combined with hypernephroid cancer. In both cases, the diagnosis of myeloma was supported by morphological examination of the bone marrow and immunochemical identification of monoclonal immunoglobulin. In female patient C, adenocarcinoma developed in the presence of polycystosis in the left kidney operated before. The diagnosis of hypernephroma was established simultaneously with the diagnosis of multiple myeloma BJX, stage III B. The patient was operated on 15 months after institution of polychemotherapy in the presence of myeloma reduction and recovery of nitrogen secretory renal function. The patient survived for 2.5 years after the operation, retaining work fitness for 2 years. She died from terminal exacerbation of myeloma. On autopsy no cancer metastases were detected. In male patient Ch. with myeloma GX, stage II A, hypernephroid cancer of the right kidney was diagnosed 7 months after the diagnosis of myeloma was established. Radical operation resulted in complete somatic and hematological compensation of the patient. The residual mass of myeloma does not manifest itself clinically after 9 courses of polychemotherapy carried out in the preoperative period. It is only detectable by the laboratory tests. The follow-up of the patient is continued.


Summary
This paper introduces a social identity perspective to job insecurity research. Worrying about becoming jobless, we argue, is detrimental because it implies an anticipated membership of a negatively evaluated group—the group of unemployed people. Job insecurity hence threatens a person's social identity as an employed person. This in turn will affect well-being and job performance. A three-wave survey study amongst 377 British employees supports this perspective. Persons who felt higher levels of job insecurity were more likely to report a weaker social identity as an employed person. This effect was found to be stable over time and also held against a test of reverse causality. Furthermore, social identity as an employed person influenced well-being and in-role job performance and mediated the effect of job insecurity on these two variables over time. Different to the expectations, social identity as an employed person and organisational proactivity were not connected. The findings deliver interesting evidence for the role of social identity as an employed person in the relationships between job insecurity and its consequences. Theoretically, this perspective illustrates the individual and group-related nature of job insecurity and offers a novel way of connecting work situations with individual well-being, behaviour and attitudes. Copyright © 2017 John Wiley & Sons, Ltd.


Human papillomavirus positive (HPV + ) oropharyngeal squamous cell carcinoma (OPC) is a distinct clinical entity within the head and neck cancers, with a unique epidemiology and, in general, a favorable prognosis. Because of this favorable prognosis, researchers have considered de-intensifying the current standard treatment of HPV + OPC in order to reduce acute and late treatment related toxicity without compromising outcome. Current ongoing trials can be divided in three main categories: de-intensification of the chemotherapy by replacing concomitant platinum-based chemotherapy with the EGFR-inhibitor cetuximab, or de-intensification of the radiation dose of either the primary radiotherapy of selected, good-responding patients after induction chemotherapy or of the adjuvant radiotherapy based on pathology features after primary surgery. Despite the good prognosis of the majority of HPV + OPC patients, a proportion of them still have poor prognosis. This unmet need has led clinical research on new treatment strategies focused on influencing the unique micro-environment of HPV + OPC with for example immunotherapy. This article summarizes the current understanding regarding the optimal treatment of non-metastatic HPV + OPC. Ongoing and published clinical trials regarding de-intensification strategies, immunotherapy and proton therapy are described focusing on the rationale and underlying evidence of these emerging treatment strategies. Nevertheless, until the results of the ongoing trials are known, the treatment of HPV + OPC in clinical practice should remain identical to the treatment of HPV negative OPC.


In this paper, we present a new path-following interior-point algorithm for -horizontal linear complementarity problems (HLCPs). The algorithm uses only full-Newton steps which has the advantage that no line searchs are needed. Moreover, we obtain the currently best known iteration bound for the algorithm with small-update method, namely, , which is as good as the linear analogue.


A crucial part of data-driven ecosystems is the management and processing of complex data structures, as well as the proper handling of the data flows within the ecosystem. To manage these data flows, data-driven ecosystems need high levels of interoperability, as it allows the collaboration and independence of both internal and external components. REST APIs are a common solution to achieve interoperability, but sometimes they lack flexibility and performance. The arising of GraphQL APIs as a flexible, fast and stable protocol for data fetching makes it an interesting approach for data-intensive and complex data-driven (eco)systems. This paper outlines the GraphQL protocol and the benefits derived from its use, as well as it presents a case of study of the improvement experienced by the Observatory of Employment and Employability (also known as OEEU) ecosystem after including GraphQL as main API in several components. The results of the paper show promising improvements regarding the flexibility, maintainability and performance, among other benefits.


The Unicode standard is an enormous step toward realizing the goal of a single computer encoding scheme for virtually all of the world's scripts. Although not all computers will necessarily have the type fonts to print all characters, at least all computers will be able to recognize what characters are required for proper display of text in almost any language. However the Unicode standard presupposes that each language has a script consisting of a finite number of agreed-upon characters. Some languages still lack such agreement. As planning has gone forward for Unicode, more and more code points are being assigned, leaving ever less conveniently accessed code points for future expansion. This article describes the Unicode project. Then it describes the special challenge of encoding Chinese characters. Finally it uses the example of Hokkien, a "dialect" of Chinese spoken by most people in Taiwan, to explore the problem of unorthodox, unstable, or unofficial scripts. Political forces and technical considerations make it difficult to include such scripts in Unicode. As Unicode becomes the "de facto" standard for writing human languages, script innovations will presumably become less and less likely to receive wide use.


2014 The energy of the Au-rich AuCu alloys is written in the Ising Model. The first 4 interaction potentials are calculated from the diffuse scattering experiments in Au75Cu25 and Au70Cu30. These potentials are compared to the results of other methods (Clapp-Moss formula, Inverse CVM method). It is shown that the calculated potentials can quantitatively account for the D.S.C. experiments, and that the energy of the fluctuations are an important part of the transition enthalpies deduced from the experiment. J. Physique 48 (1987) 1703-1708 OCTOBRE 1987,


Background: Prognosis of patients with metastatic malignant melanoma is very poor and partly due to high resistance to conventional chemotherapies. The study's objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma.Methods: This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. Trail registration: Clinical Trials, ID: NCT03383237. Registered on 24 December 2017. URL of trail registry record: https://register.clinicaltrials.gov. Results: Fifteen patients were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.33% response rate. Eleven patients had stable disease, with a DCR of 86.67%.The median OS was 12.0 months. The most common clinically significant grade 3 or 4 toxicities included hypertension and canker sore. No treatment-related deaths occurred.Conclusions: Apatinib showed antitumor activity as a second or first-line therapy in patients with malignant melanoma. The toxicity was manageable.


Objective:
 To determine the effectiveness of home electronic blood pressure cuffs to improve compliance with both disease-specific and the general Practice Performance Measures (PCPI) blood pressure goals in the high risk underserved population in a safety-net urban medical center.

 Background:
 Achieving recommended blood pressure goals in an underserved patient population with a high cardiac disease burden is challenging. Intensive, clinician-led health maintenance programs have shown promise but are difficult to implement on a wide scale. The decreasing cost of electronic blood pressure cuffs offers an opportunity to provide patient-focused treatment.

 Methods:
 Twenty-two consecutive patients who were not at either their disease-specific or PCPI goal of <140/90mmHg received an electronic blood pressure cuff for home use as part of their optimal medical treatment. This was a prospective, before-after study. Patients were relatively young (mean 59 years), had a high prevalence of coronary disease (32%), heart failure (37%) , valvular disease(37%) and preserved left ventricular ejection fraction (49%). In-clinic blood pressure measurements were collected. The time to the cross-over from medical therapy to medical therapy with a blood pressure cuff was an average 184.4 days (3.2 encounters with clinicians for medication changes) and average of 75.8 days (1.1 encounters) after the cross-over to follow-up. A paired student T-test was used for statistical comparison between the two groups.

 Results:
 There was a statistically significant difference in the systolic blood pressures after the medical treatment period compared to the cross-over arm 143.3mmHg (CI 135.3-151 p-value=0.1) vs.134.6mmHg and diastolic pressure 81.09mmHg (CI 75.4-86,75 p-value=0.05) vs. 72.24mmHg. Overall compliance with the PCPI recommendation was higher in the cross-over arm (45% vs. 55%) as well as with the disease specific recommendations (18% vs. 25%).

 Conclusion:
 There was a statistically significant improvement in both systolic and diastolic blood pressures in the underserved ambulatory patient with a home blood pressure cuff. There was also an improvement in compliance both with the PCPI and disease-specific goals guidelines.


The prime motivation of our work is to balance the inherent trade-off between the resource consumption and the accuracy of the target tracking in wireless sensor networks. Toward this objective, the study goes through three phases. First, a cluster-based scheme is exploited. At every sampling instant, only one cluster of sensors that located in the proximity of the target is activated, whereas the other sensors are inactive. To activate the most appropriate cluster, we propose a nonmyopic rule, which is based on not only the target state prediction but also its future tendency. Second, the variational filtering algorithm is capable of precise tracking even in the highly nonlinear case. Furthermore, since the measurement incorporation and the approximation of the filtering distribution are jointly performed by variational calculus, an effective and lossless compression is achieved. The intercluster information exchange is thus reduced to one single Gaussian statistic, dramatically cutting down the resource consumption. Third, a binary proximity observation model is employed by the activated slave sensors to reduce the energy consumption and to minimize the intracluster communication. Finally, the effectiveness of the proposed approach is evaluated and compared with the state-of-the-art algorithms in terms of tracking accuracy, internode communication, and computation complexity.


ABSTRACT. Diabetes mellitus contributes greatly to morbidity, mortality, and overall health care costs. In major part, these outcomes derive from the high incidence of progressive kidney dysfunction in patients with diabetes making diabetic nephropathy a leading cause of end-stage renal disease. A better understanding of the early dysfunctions observed in the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review proposes a "tubulo-centric" view of glomerular function in early type I diabetes mellitus. The following are particularly discussed ( 1 ) the primary role of an increase in reabsorption by the proximal tubule in early glomerular hyperfiltration, ( 2 ) the role of sodium-glucose cotransport and tubular growth under these conditions, and ( 3 ) the primary role of reabsorption by the proximal tubule for the paradoxical relationship between dietary salt and glomerular filtration rate. Finally, an outline is presented of potential therapeutic implications for the prevention of diabetic kidney disease. E-mail: email@example.com


Osteosarcoma (OS) is the most common primary cancer of the bone affecting children and adolescents. While over the last two decades the neoadjuvant chemotherapy has improved survival of the patients with resectable OS, the prognosis for unresectable or recurrent tumors remains poor due to the lack of effective treatment. Given that a majority osteosarcomas overexpress HER2, a phase II clinical trial of anti-HER2 antibody trastuzumab in conjunction with chemotherapy has been carried out to treat metastatic OS. However, no significant therapeutic benefit was observed. We recently reported that association of anti-CD20 antibody rituximab with a nanomaterial graphene oxide (GO) substantially enhances the anti-lymphoma activity of the antibody. Here we have studied antitumor activity of GO-associated trastuzumab (TRA). Similar to RTX, TRA could be stably associated with functionalized GO through non-covalent interactions, and GO-associated TRA (TRA/GO) showed markedly enhanced HER2 binding activity with capacity to aggregate (cap) HER2 on the target cells. Treating HER2+ OS as well as Ewing's sarcoma cell lines in culture with TRA/GO resulted in rapid sarcoma cell death within 12 hr, while free TRA or the cytotoxin-conjugated TRA (ado-trastuzumab emtansine) showed no significant cytotoxic effects. TRA/GO manifested no cytotoxicity to human lymphocytes, in contrast to chemotherapeutic drugs such as doxorubicin and oxaliplatin. We find that the ability to kill the sarcoma cells results from the unique capacity of TRA/GO to simultaneously induce oxidative stress as well as intense detrimental HER2 signaling, which leads to a complete disappearance of a major tyrosine-phosphorylated protein and caspase 8, and a partial loss of RIPK1 along with an increase in RIPK3 levels within 5 min, followed by necroptosis of the target cells. Intravenous administration of TRA/GO rapidly eradicated established xenograft human OS in the lung as well as at subcutaneous locations in NOD/rag ko /g ko immunodeficient mice in the absence of chemotherapy, resulting in indefinite survival of the animals. In contrast, free TRA treatment failed to do so. No appreciable side effects were observed of TRA/GO in vivo. These results therefore demonstrate a novel strategy to substantially enhance the therapeutic capacity of anti-cancer antibodies. Given the increasing variety of human malignancies that are found to overexpress Her2, including sarcomas, carcinomas and neurological malignancies, our findings should have broad therapeutic implications. As TRA/GO does not harm lymphocytes, TRA/GO-based therapy may constitute a unique opportunity to implement immunotherapy that is now known to play an important role in control tumor progression. Citation Format: Xinjian Chen. Targeting osteosarcoma with graphene oxide-associated anti-HER2 antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 63. doi:10.1158/1538-7445.AM2017-63


Correlations between Charpy energy transition temperatures and other fracture mechanics parameters have been widely used for many years in steel failure analysis and design. The primary value transferred often has been a transition temperature, such as the 27 J transition temperature. This approach does not consider the scatter in the transition temperature or in the overall Charpy data. This work uses a scatter assessment tool developed by Orynyak et al. and applies it to a wider variety of steels and weldments to see whether it can provide a second parameter to be transferred to fracture assessment. Examples include pipeline steel and structural steel, as well as weldments in both the weld metal and heat-affected zone. While Charpy transition scatter is expected to be high in heat-affected zones, examples can be found in base metals with similarly high scatter.


MAML2 rearrangements have been previously described for hidradenomas and muco-epidermoid carcinomas (MEC). However, one report showed EWSR1 rearrangement in both tumours. In this study, EWSR1 and MAML2 translocation were investigated in hidradenomas and MECs. Specimens from thirteen MECs of the salivary glands and twenty hidradenomas of the skin were evaluated. Fluorescence in situ hybridisation (FISH) studies with EWSR1 and MAML2 break-apart probes were used. Forty percent of hidradenomas and 84.6% of MECs showed a positive MAML2 break signal. EWSR1 break signal was absent in hidradenomas. Only two MECs showed positive EWSR1 signal and were, thus, reclassified as clear cell carcinoma (CCC). A statistically significant relationship was also observed between clear cells containing hidradenomas and the FISH status. Despite the previous study, EWSR1 translocations could not be established in hidradenomas and MECs. The study further suggests that evaluation of EWSR1 might be obligatory for the correct diagnosis of MAML2-negative MECs to exclude the chance of CCCs. The present study also supports the notion that MAML2 can be used as a marker for hidradenomas and MECs.


Based on the time-correlated leakage model and fuzzy random probability theory, a formula for calculating fuzzy random reliability of sealing performance of bolted flanged connections was derived. The optimization variables were defined according to the sensitivity analysis of design parameters on fuzzy reliability of sealing performance. A fuzzy reliability optimization design method of flange was investigated, in which both the tightness of bolted flanged connections and the strength of flange were taken into consideration. As an example, an integral welding necked pipe flange was designed according to the optimization design method proposed in this paper. The designed flange not only satisfies the requirements of flange strength and sealing reliability of connections, but also its weight is reduced by 16% compared with that prescribed in the standard.


Driving intentions can not intervene in the shift curve according to the change rate of throttle opening and road information. Considered the change rate of throttle opening and road information, the fuzzy control method was used to amend the economic conditions of the shift curve. The results show that the fuzzy control method adding driving intention can amend shift curve of the economic conditions and taking into account economic and power performance requirements, in line with the driving intentions to operate shift curve in accordance with the road information.


The present study evaluated a training program for probation officers based on the risk-need-responsivity (RNR) model of offender rehabilitation. A total of 80 officers were randomly assigned to either training or a no training condition. The probation officers then recruited 143 probationers and audiotaped their sessions at the beginning of supervision, 3 months later, and 6 months later. The audiotapes were coded with respect to the officers' adherence to the RNR model. The experimental probation officers demonstrated significantly better adherence to the RNR principles, with more frequent use of cognitive-behavioral techniques to address the procriminal attitudes of their clients. Finally, the analysis of recidivism rates favored the clients of the trained officers. The findings suggest that training in the evidence-based principles of the RNR model can have an important impact on the behavior of probation officers and their clients.


Abstract. Global retrievals of near-infrared sun-induced chlorophyll fluorescence (SIF) have been achieved in the last few years by means of a number of space-borne atmospheric spectrometers. Here, we present a new retrieval method for medium spectral resolution instruments such as the Global Ozone Monitoring Experiment-2 (GOME-2) and the SCanning Imaging Absorption SpectroMeter for Atmospheric CHartographY (SCIAMACHY). Building upon the previous work by Guanter et al. (2013) and Joiner et al. (2013), our approach provides a solution for the selection of the number of free parameters. In particular, a backward elimination algorithm is applied to optimize the number of coefficients to fit, which reduces also the retrieval noise and selects the number of state vector elements automatically. A sensitivity analysis with simulated spectra has been utilized to evaluate the performance of our retrieval approach. The method has also been applied to estimate SIF at 740 nm from real spectra from GOME-2 and for the first time, from SCIAMACHY. We find a good correspondence of the absolute SIF values and the spatial patterns from the two sensors, which suggests the robustness of the proposed retrieval method. In addition, we compare our results to existing SIF data sets, examine uncertainties and use our GOME-2 retrievals to show empirically the relatively low sensitivity of the SIF retrieval to cloud contamination.


The impact of highly cationic density polymers such as modified poly-ethyleneimine(PEI), as anionic trash catcher(ATC) on the drainage and retention properties of aspen alkaline hydrogen peroxide mechanical pulp(APMP) in different CPAM(/bentonite) systems was studied. The results showed that Modified PEI could improve the retention and drainage properties of CPAM/ bentonite systems; when adding 0.02% dosage of PEI, the drainage and retention rate were increased by 16.0% and 1.9% respectively as compared to control with 0.03% dosage of the CPAM with 1.55 meq/g cationic charge density and 4.9 million molecular weight, which denoted by CPAM(W/W); the drainage and retention rate were increased by 28.6% and 3.0% respectively as compared to the control with 0.03% dosage of CPAM(W/W) and 0.3% dosage of bentonite. The CPAM with more cationic charge density and higher molecular weight than the CPAM(W/W) is denoted by CPAM(W/O) in this paper. The microparticle system which consisted with PEI and the CPAM(W/O)(/bentonite) was slightly superior to the PEI/CPAM(W/W)/bentonite system. When 0.02% dosage of PEI and 0.03% dosage of CPAM were added respectively, PEI/CPAM(W/O) made the drainage and retention rate increased by 9.5% and 1.9% respectively as compared with PEI/CPAM(W/W).


The productivity of introduced and native-based pastures across the Monaro region of NSW is often constrained by a low legume content. Full pasture renovation is frequently precluded by landscape, soil or economic constraints with producers often spreading legume seed with fertiliser in an attempt to increase the legume content of pastures. Four methods of legume introduction into an existing pastures (surface broadcasting and direct drilling with and without a pre-sowing glyphosate knockdown) at two landscape positions (north and south facing aspect) for four legume species, subterranean clover (Trifolium subterraneum), Caucasian clover (T. ambiguum), Talish clover (T. tumens) and lucerne (Medicago sativa), were investigated. Direct drilling after a glyphosate knockdown was the most successful method of introduction with subterranean clover achieving the highest seedling density. However, after 12 years, few legumes could be found on the north-facing aspect and subterranean clover had not survived on the south facing aspect. Legumes were found only in the direct drilled-glyphosate knockdown treatment; lucerne having the highest plant density and herbage availability. Where legume treatments had failed, populations of tall speargrass (Austrostipa scabra), a native perennial grass, had returned to their original density. A. scabra density was significantly lower on the south facing aspect in the lucerne and Caucasian clover treatments. There is capacity to introduce legumes into existing pastures but seed-soil contact and reduction in competition from existing pasture species at establishment is crucial to long-term persistence


Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co‐occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems.


The currunt solution for building transducers is done with MEMS technology (microelectromechanical systems). The building process is complex and generally takes a lot of time. It is therefore not possible to completely design and
build a MEMS device at short notice. To increase the throughput of the process 3D printing might be used. This research is focussed on the investigation of
the mechanical properties of 3D printed parts from Objet and DLP, printed as small as possible, in order to investigate the usability of 3D printed struc-
tures. Test structures designed in Solid Works were printed with Objet and DLP printers. These designs were characterised with respect to minimum block
size, accuracy, Young's Modulus and Shear Modulus of the printed structures.
The minimum block size and accuracy are measured with an optical micro-scope. The Young's Modulus is measured dynamically and statically and the Shear Modulus only statically. It was possible to measure all quantities. Only
the dynamically and statically measured Young's Modulus results showed large deviations. This was due to a large error made in the static measurements. The minimum block size ranges between 150�m and 500�m for DLP and 250�m and
300�m for Objet printed structures. The accuracy achieved for the DLP was the best in the xy-plane. The accuracy for the Objet printer was approximately the same in all planes due to the use of support material. The Young's Mod-
ulus and Shear Modulus of the Objet printed items where max 2.5�0:15 GPa and 0.24�0:018 GPa and for the DLP 1.1�0:06 GPa and 0.012�0:001 GPa.
Also some anisotropy was observed; the Young's Modulus was the highest in the xy-plane and the smallest in the z direction. With those indicated Young's
Modulus and Shear Modulus known it is possible to design transducers. The minimum block size and accuracy are still to high to reach the same accuracy as MEMS technology, however it is possible to build transducers at an bigger size, furthermore it is possible to increase the manufacturing process of transducers with 3D print technolgy.


More than 40 diseases have been associated with the misfolding of peptides (or proteins) that form fibrils with a very specific morphology. These peptides classified as amyloidogenic peptides have been implicated in the development of Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, Hungtinton's Disease etc. To date, these diseases have no cure, only therapies that can ameliorate the symptoms to a degree. Inhibition of the amyloidogenesis of these peptides has been proposed as a possible treatment option. While small molecules have been heavily tested as inhibitors of amyloidogenesis, peptides have emerged as potential inhibitors. In this work, the ability of a set of designed hairpin peptides to inhibit the amyloidogenesis of two different systems, α-synuclein (implicated in Parkinson's Disease) and human amylin (implicated in Type II Diabetes) is tested. Using circular dichroism and thioflavin T fluorescence, the ability of these peptides to inhibit amyloidogenesis is tested. The binding loci of these inhibitors to α-synuclein are also explored. The use of peptides as antimicrobials on the other hand is not a novel concept. However, most antimicrobial peptides, both natural and designed, rely heavily on covalent stabilizations in order to maintain secondary structure. In this study, non-covalent stabilizations are applied to a couple of natural as well as designed antimicrobials in order to study the effects of secondary structure stabilization on biological activity.


Abstract Background In patients with haemophilia, evidence suggests that the physical examination alone is not sensitive enough to detect small amounts of blood within a joint. Attention has shifted to methods of improving the sensitivity of the physical examination through adding diagnostic modalities such as point-of-care ultrasonography (POC-US). Proficiency with the physical examination and understanding of the role of POC-US are important competencies for physiotherapists. Despite training, implementation of POC-US by physiotherapists in haemophilia treatment centres in Canada has been mixed. Aim Using a theory-based approach, the aim of the current study is to achieve expert consensus regarding the barriers to physiotherapy performed POC-US in haemophilia treatment centres in Canada using a modified Delphi approach. Materials and Methods Using the Knowledge-to-Action Framework and the Consolidated Framework for Implementation Research (CFIR), a modified Delphi approach was completed using the Modified BARRIERS Scale (MBS). Participants were blinded and consensus was reached over three rounds at the Canadian Hemophilia Society's annual three-day conference. Results Twenty-two physiotherapists participated; 20 participants completed Round 1, and 21 completed Rounds 2 and 3. Four items of the MBS reached consensus: 1) The physiotherapist does not have time to read research related to POC-US; 2) The physiotherapist is isolated from knowledgeable colleagues with whom to discuss POC-US; 3) Administration will not allow POC-US implementation; 4) There is insufficient time on the job to implement new ideas. All four consensus items can be mapped to one domain of the CFIR: the inner setting. Conclusion The haemophilia treatment centre within a healthcare organisation appears to be an important target for addressing barriers to the implementation of physiotherapy performed POC-US.


Background Protein tyrosine phosphatase receptor type D (PTPRD) is a putative tumor suppressor in several cancers including head and neck squamous cell carcinoma (HNSCC). STAT3 is a frequently hyperactivated oncogene in HNSCC. As STAT3 is a direct substrate of PTPRD, we sought to determine the genetic or epigenetic alterations of PTPRD that contribute to overactive STAT3 in HNSCC. Methods We analyzed data from The Cancer Genome Atlas (TCGA) and our previous whole-exome sequencing study and summarized the mutation, methylation, and copy number status of PTPRD in HNSCC and other cancers. In vitro studies involved standard transfection and MTT protocols, as well as methylation-specific PCR. Results Our findings indicate that PTPRD mutation, rather than methylation or copy number alteration, is the primary mechanism by which PTPRD function is lost in HNSCC. We demonstrate that overexpression of wild-type PTPRD in HNSCC cells significantly inhibits growth and STAT3 activation while PTPRD mutants do not, suggesting that mutation may lead to loss of function and subsequent hyper-phosphorylation of PTPRD substrates, especially STAT3. Importantly, we determined that HNSCC cells harboring an endogenous PTPRD mutation are more sensitive to STAT3 blockade than PTPRD wild-type cells. We additionally found that PTPRD mRNA expression does not correlate with pSTAT3 expression, suggesting that alterations that manifest through altered mRNA expression, including hypermethylation and gene copy number alterations, do not significantly contribute to STAT3 overactivation in HNSCC. Conclusion PTPRD mutation, but not methylation or copy number loss, may serve as a predictive biomarker of sensitivity to STAT3 inhibitors in HNSCC.


Brain-computer interfaces (BCI) allow for communication between the human brain and computers. They have been used to create systems able to generate control over a software or mechatronic device, becoming an important tool for the rehabilitation of handicapped people, especially for patients with quadriplegia. Due to the importance of BCIs, any attempt to improve their response has a great value. The work described in this paper consists of the evaluation of various stimuli applied to improve the training of a BCI based system. The device is the Emotiv® EPOC which includes a Software Development Kit (SDK) to train the system. During the usual training of the SDK; images, videos, thoughts, movements and gestures were used as stimuli to improve the users' skills for accomplishing specific actions. After the evaluation of these stimuli, they were ranked according to their effectiveness. Finally, a powered wheelchair was controlled using the Emotiv® EPOC by applying the best-ranked stimulus and an assessment protocol was used in order to evaluate the performance of users driving the wheelchair with the BCI, with satisfactory results.


Abstract. In this paper the development of a cable bundle test bench is described and exemplary results of the systematic measurement of cable bundles for automotive EMC tests are presented. The test bench consists of particularly developed adapter boxes and switch matrices, which allow together with a network analyzer to perform a network analysis with up to 32 ports and up to 1 GHz. Calibration and deembedding procedures are described and validated. Cable bundles that are characteristic to automotive EMC tests are investigated with respect to the number of wires within the cable bundle, the class of the cable bundle and the type of wires.


Aim of this study was to investigate the application of normalized mean of the empirical Higuchi fractal dimension (FD) distributions, as a new approach to analyze the spontaneous bioelectrical activity of garden snail (Helix pomatia) Br neuron. The effect of ouabain on modulation of Br neuron bursting activity before and after the exposure to 10 mT static magnetic field (SMF) was observed by analyzing the following parameters: action potential (AP), interspike interval (ISI) and interbursting interval (IBI) components. Normalized mean of the empirical FD distributions were formed for the following experimental conditions: Control 1, Ouabain 1, Control 2, SMF 2, ASMF 2, Control 3, SMF 3 and Ouabain ASMF 3. Our main results have shown that ouabain without SMF induced increase in participation of AP and a decrease in participation of IBI components compared to the first control condition. However, in the presence of 10 mT SMF, ouabain-induced changes of measured parameters of Br neuron activity were less pronounced compared to the third control condition. We have shown that normalized mean of the empirical FD distributions is a useful method for detecting the changes in AP, ISI, and IBI components of complex bursting activity in altered physiological states.


Set in the autumn of 2005, this case recounts the remarkable performance record of Value Trust, a mutual fund managed by William H. "Bill" Miller III at Legg Mason, Inc. The case describes the investment style of Miller, whose record with Value Trust has beaten the S&P 500 14 years in a row. The tasks for the student are to assess the performance of the fund, consider the sources of its success, and decide on the sustainability of Miller's performance. Consistent with the introductory nature of the case, the analysis requires no numerical calculations. The instructor should not be deceived, however: the absorption of capital-market background and the implications of financial concepts in the case will fully occupy the novice. This case updates and replaces "Peter Lynch and the Fidelity Magellan Fund" (UVA-F-0777) and "The Fidelity Magellan Fund, 1995" (UVA-F-1126). The case is intended for use in the opening stages of a finance course. It provides a nontechnical introduction to the U.S. equity markets and lays the foundation for some basic concepts in finance.


Five TnphoA fusions to vir-repressed genes (vrg genes) have been identified in the respiratory pathogen Bordetella pertussis. A comparison of vrg DNA sequences suggests a consensus DNA element within the coding regions of four of five vrg genes. To determine the role of this DNA sequence in vrg regulation, a nucleotide substitution mutation in the conserved region of vrg-6 was isolated. This mutant showed constitutively high levels of expression in the absence of antigenic modulators, MgSO4 and nicotinic acid, suggesting that this DNA element may be a control site for vrg repression. Moreover, Northern (RNA) analysis and transcriptional fusion analysis suggest that vrg genes are regulated at the transcriptional level. To determine whether sequences in the coding region were sufficient to respond to antigenic modulation, a vrg-6::TnphoA promoter deletion plasmid that contained a heterologous promoter driving the expression of vrg-6 coding sequences from the vrg-6 translation start site to the TnphoA fusion junction was constructed. This heterologous construct responded to modulators in a vir-dependent fashion, indicating that sequences upstream of the coding sequence are not required for antigenic modulation. Southwestern (DNA-protein) analysis and mutational studies suggest that the vrg consensus DNA sequence is specifically recognized by a 34-kDa vir-activated gene (vag) product, whose binding results in down-regulation of vrg transcript levels. We conclude, at least for the vrg::TnphoA fusion strains, that a site on the DNA that corresponds to a consensus sequence located in the vrg coding region is sufficient to confer the transcriptional regulation (repression) of vrg genes when B. pertussis strains are grown under nonmodulating conditions.


According to poor computational accuracy at small to median sample sizes of Monte Carlo ( MC ) simulation techniques in estimating the probability failure of mechanical structures, the number theoretical net ( NT-net ) simulation method is proposed to reduce computing effort. Several key concepts, such as good point set, good-lattice point ( glp ), discrepancy and NT-net method, are defined. The sampling stategy is improved by introducing NT-net that can provide better convergent rate over MC. The new method is used to estimate failure probability of the side impact bar on the car door. Results indicate the computational effort needed by NT-net for the same accuracy is about 1/12 of that needed by the MC-based method, and the obtained results are more stable.


An objective method is developed for forecasting the occurrence and intensity of showers. A composite moisture-stability parameter is designed which approximates the current structure of the atmosphere. This parameter is then combined with a vorticity-advection parameter which dictates the changes of the current structure. The system is designed for the summer season and is tested for Chanute Air Force Base, Illinois with a resultant skill score and per cent correct of 0.74 and 90 respectively.


Some of elements in our society have responded the expansive development and growth of syariah banking contemptuously, moreover, among some moslems themselves.The contemptuous view of Islamic banking showed by people's trust for Syari'ah Banking has been still relatively low. It shown by the moslem participation on investment and capital movement. Indeed, some of moslem intellectuals have criticized syariah banking, they considered of the transactions done by Islamic bankings, even, in contrary with its own-concept. In other words, it's in compatible with syari'ah spirit. The contemptuous view can't be separated from capitalism economic that's been deeply rooted in our society. Learning the problem surrounding syari'ah finance institution and some of its positive value, it's urgently required for this institution to improve its profesionality, in order to arise its image, next in future it hopefully able to spread wider merciful benefit . The effort increasing profesionality have to more attention of the relationship between syari'ah finance institution and consumers, a commitment of continuous inovation and also a balanced consideration of decision maker research. Operationally, profesionality improvement of syari'ah finance institution able to apply the Criteria Grade of Syariah banking Choice in Yogyakarta as its measurement. Key words: Persepsi, Pandangan, Lembaga Keuangan Syari'ah, Profesionalitas


This paper focuses on how characteristics of regions pertaining to local information about product varieties and markets as well as networks for the transmission of information about innovation opportunities influence the arrival of innovation ideas to existing and potential entrepreneurs. We formulate a model where entrepreneurs or innovating firms introduce new products in a quasi-temporal setting. Market conditions are characterized by monopolistic competition between varieties belonging to the same product group, in which there is entry and exit of varieties. Firms innovate in response to the arrival of innovation ideas. To realize these ideas firms have to make an R&D investment and a firm's decision to export a variety to a new market is associated with a market channel investment. The theoretical model is used as a reference when formulating two regression models, with which we estimate factors that can explain the introduction of new export varieties by firms in different regional milieus. In one model we examine the emergence of new export firms, and in the second model we investigate the appearance of new export varieties. Results are consistent with the assumption that knowledge and information flows have a positive influence on the frequency of arrival of innovation ideas to firms.


Wireless sensor networks have emerged as an exciting technology for a wide range of important applications that acquire and process information from the physical world. Grid computing has evolved as a standards-based approach for coordinated resource sharing. Sensor grids combine these two promising technologies by extending the grid computing paradigm to the sharing of sensor resources in wireless sensor networks. There are several issues and challenges in the design of sensor grids. In this paper, we propose a sensor grid architecture, called the scalable proxy-based architecture for sensor grid (SPRING), to address these design issues. We also developed a sensor grid testbed to study the design issues of sensor grids and to improve our sensor grid architecture design


As with any other open source field, there are countless far-reaching advantages in open hardware licensing, as opposed to its proprietary counterpart. This paper takes the example of a low-cost portable mechanical ventilator design and considers the effect of the application of the three different variants of the newly-released CERN Open Hardware Licence Version 2. This paper considers the importance of licensing, and demonstrates how open hardware licensing can facilitate efficient further development of a project, improve its safety and reliability, and encourage collaboration. Most importantly, open hardware licensing allows anyone to freely use, study, modify and distribute improvements to project design, and make, sell or otherwise distribute products made to that design, making it a cost-effective means of developing and deploying the device throughout the world, from the most developed to the most vulnerable territories. Finally, this paper argues that open hardware licensing also encourages economic activity whilst it protects third-party intellectual property rights.


Basis behavior is generally considered to be the major determinant of hedging success or failure. In the course of our work as contract designers for Chicago Mercantile Exchange Inc., we have come to the conclusion that there are many misconceptions and incorrect statements made about "the basis" among practitioners and academics alike. Our work suggests that basis values, how they are measured, what they represent and how they are interpreted may differ widely from one commodity contract to another due to differences in the specifications of the underlying futures market, as well as differences in the structure of the underlying cash market.


1 The effects of an intravenously administered sumatriptan analogue were examined on c‐fos‐like immunoreactivity (c‐fos‐LI), a marker of neuronal activation, evoked within trigeminal nucleus caudalis (TNC) and other brain stem regions 2 h after intracisternal injection of the irritant, capsaicin (0.1 ml, 0.1 mm), in pentobarbitone‐anaesthetized Hartley guinea‐pigs. 2 C‐fos‐LI was assessed in eighteen serial sections (50 μm) using a polyclonal antiserum. A weighted average, reflecting total expression within lamina I, IIo of TNC was obtained from three representative levels (i.e., at −0.225 mm, −2.475 mm and −6.975 mm.) 3 Capsaicin caused significant labelling within lamina I, IIo, a region containing axonal terminations of small unmyelinated C‐fibres, as well as within the nucleus of the solitary tract, area postrema and medial reticular nucleus. A similar distribution of positive cells was reported previously after intracisternal injection of other chemical irritants such as autologous blood or carrageenin. 4 Pretreatment with a conformationally restricted sumatriptan analogue (with some selectivity for 5‐HT1B and 5‐HT1D receptor subtypes) CP‐122,288, reduced the weighted average by approximately 50–60% (P<0.05) in lamina I, IIo at ≥ 100 pmol kg−1, i.v., but did not decrease cell number within area postrema, nucleus of the solitary tract or medial reticular nucleus. A similar pattern was reported previously following sumatriptan, dihydroergotamine or CP‐93,129 administration after noxious meningeal stimulation. 5 We conclude that modifications at the amino‐ethyl side chain of sumatriptan dramatically enhance the suppression of c‐fos expression within TNC, a finding consistent with its remarkable potency against neurogenic plasma protein extravasation within dura mater. CP‐122,288 and related analogues may serve as an important prototype for drug development in migraine and related headaches.


Thermal protection is one of the most important aspects of any motor control system. This paper proposes a stator winding temperature estimation method for the thermal protection of inverter-fed electric motors. By modifying the space vector pulsewidth modulation in an open-loop motor drive, a dc voltage can be intermittently injected into the motor. The stator temperature can be estimated by measuring only the dc component of the phase current under both constant- and variable-load conditions. The evaluation of the resultant torque pulsation and the compensation for serial resistances are also discussed. The proposed stator temperature estimation method is validated from experimental results under variable-load conditions and both healthy and impaired cooling conditions. The error in the stator temperature estimation is within 8 °C under different operating conditions. The significance of this method lies in its non-intrusive nature: only current sensors are required for implementation the normal operation of the motor is not interrupted.


Carotid endarterectomy (CEA) of the carotid artery prevents subsequent ischemic stroke. Sometimes carotid artery stenting (CAS) is an alternative. Physicians should be aware of short and long-term postprocedural complications of CAS and CEA. Section 1 concerns hemodynamic changes, their effect on the development of new cerebral ischemic lesions, and clinical outcome. Both treatments had a decrease in blood pressure (BP) at discharge. BP decreased more after CAS (mean difference (MD) between-groups in SBP 10.3 mmHg, 95%CI, 7.3 to 13.3). During follow-up BP-changes were not different between groups. However, fewer CAS-patients used antihypertensive medication during follow-up; CAS may lessen the need for antihypertensive medication more than CEA. The occurrence of periprocedural hemodynamic depression (severe bradycardia, asystole, or hypotension requiring treatment) and hypertension requiring treatment was assessed. Hemodynamic depression occurred in 13.8% CAS-patients and in 7.2% CEA-patients (relative risk (RR), 1.9; 95%CI 1.4 to 2.6). Hypertension requiring treatment occurred less after CAS (RR, 0.2; 95%CI, 0.1 to 0.4). The 30-day composite outcome of stroke, myocardial infarction (MI), or death occurred in 60 (7.8%) of CAS-patients and in 33 (4.0%) of CEA-patients. There was no significant association between hemodynamic complications and the composite outcome; thus the occurrence of hemodynamic depression after CAS does not explain its excess of major perioperative events. After CAS, patients with hemodynamic depression had 3-times more DWI lesions, compared with those without hemodynamic depression (RR, 3.36: 95%CI, 1.73 to 6.50). The number of lesions after CEA was too small. Section 2 describes cognitive consequences of carotid artery revascularization. The cognitive effects of CAS and CEA for symptomatic carotid artery stenosis were assessed. CAS had a larger decrease in cognition than CEA, but compared with CEA this was not statistically significant: -0.17 (95%CI, -0.38 to 0.03). DWI lesions were assessed in a subpopulation and occurred twice more after CAS than after CEA (RR, 2.1; 95%CI, 1.0 to 4.4). Cerebral white matter lesions (WML) are associated with cognitive impairment, and carotid revascularization with cognitive worsening or improvement. The relation between WML-severity and cognitive change after treatment was assessed. All patients declined in cognition: MD -0.21 (95%CI, -0.32 to -0.09). However, the sumscore-change was independent of WML-load: MD no-to-mild, -0.15 (95%CI, -0.39 to 0.09), moderate, -0.27 (95%CI, -0.48 to -0.06); and severe, -0.21 (95%CI, -0.40 to -0.04). In patients with a fetal-type posterior cerebral artery (FTP) (an embryonic variant that supplies the posterior cerebral artery (PCA) mainly by the internal carotid artery), ipsilateral stenosis is likely to result in a larger area with hypoperfusion than with a normal PCA. These patients could benefit more from revascularization. We compared the cognitive effects between patients with an FTP and those with a normal PCA. The cognitive sumscore decreased more in the 13 FTP-patients; by -0.28 (95%CI, 0.10 to 0.45) and by 0.07 (95%CI, 0.002 to 0.15) in 85 patients with a normal PCA (MD, -0.20; 95%CI, -0.40 to -0.01). The challenge for further studies assessing outcome after carotid revascularization is to identify the patients at risk of postprocedural major adverse events and cognitive decline.


Due to the error-prone nature of modern cache coherence protocols, in all modern processor design flows these protocols are formally specified at the level of interleaving atomic transactions and model checked. Explicit state enumeration methods are almost always used for coherence protocol verification, as symbolic methods have failed to deliver advantages in this area. The move towards multicores implies that hierarchical organizations of several different cache coherence protocols will be employed in the future. The product state space of all these protocols jointly operating in a multicore cache hierarchy is beyond the reach of all available explicit state model checkers. In our previous work, an assume guarantee technique that allowed these protocols to be handled for the first time was reported. In this approach, a method was proposed to create a set of initial abstract protocols Mi % where each Mi simulates the given hierarchical protocol. After the set of initial Mi's are created, verification consists of dealing with Mi's in an assume guarantee manner, refining each Mi in the process. The drawbacks of this work were: (i) even a single Mt modeled more than one level of the coherence protocols, thus still creating very large product spaces; (ii) details such as non-inclusive caching hierarchies could not be handled; (iii) the initial Mi's were created manually, which is tedious and error prone. This paper overcomes all these limitations, handling non-inclusive caching hierarchies, bringing about a 95% reduction in the total state space encountered during any single explicit enumeration search, and requiring only a few such runs to finish verification.


With the absence of official aid organisations from Cambodia until the 1990s, NGOs have been the main support to development in the country. In June 1990,
Oxfam initiated the Takeo Irrigation Structures Project (KAM 215) in Takeo Province, southern Cambodia, to increase the technical skills of provincial level irrigation technicians; support locally managed irrigation schemes; and develop contacts with local communities which
would enable Oxfam to develop other community-based programmes. The major inputs were Technical Assistance
(an Engineer), construction materials and equipment, capital for a loan scheme to farmers in a pilot project, salary subsidies for Takeo Provincial Office of
Hydrology counterparts, and operation and maintenance of vehicles and equipment.
Ian Smout and Peter Robertson undertook an external evaluation of the project for Oxfam in April-May 1993. This paper is drawn from the evaluation report.


The contemporary youth studies are mostly metrocentric. As a result, rural youth often find themselves outside the focus of researchers' attention being marginalized in comparison with urban youth whose experience and lifestyle are perceived as a normative model. In these conditions, rural space is labeled as illegitimate and structurally depriving for youth. This approach is criticized by researchers who work in the tradition of the cultural geographies of childhood and youth and take into account complex, often contradictory but still unique and autonomous experiences of today's young people living in rural areas. The article is based on 59 biographical interviews and describes how Russian rural youth comprehend belonging to places in three rural localities. The authors single out three types of prerequisites defining the place attachment and local identities among young people: rational choice, biographical rootedness, and community rootedness.
Acknowledgments. The study was implemented in the framework of the Basic Research Program at the National Research University Higher School of Economics (HSE) in 2015-2016.
We thank our colleagues from the Centre for Youth Studies at NRU HSE in St. Petersburg who participated in interviewing the respondents and whose excellent and professional work was indispensable for writing this article.


SUMMARY   This article attempts to draw some factual and authoritative parallels to establish the law of intellectual property with respect to patents as it is in some selected forums. Several principles of patents generally, and ENABLING PUBLIC DISCLOSURE as it relates to NOVELTY are discussed in comparison with applicability of these principles in other territories and countries, such as the United States of America, Japan and Nigeria. The requirement of ENABLING DISCLOSURE during application is discussed with regards to previous applications and its effect on novelty, as well as the effect of a disclosure to the public before application. Relevant decided cases have been employed to clearly view ENABLING PUBLIC DISCLOSURE and an attempt is made to effectively analyse, critique, and propose steps for better application.


Background In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants' efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Methods Narrative review based on a comprehensive search of the literature. Results It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased risk of suicide and that they have a higher rate of all-cause mortality than matched controls. Conclusion The strong reliance on industry-funded research results in an uncritical approval of antidepressants. Due to several flaws such as publication and reporting bias, unblinding of outcome assessors, concealment and recoding of serious adverse events, the efficacy of antidepressants is systematically overestimated, and harm is systematically underestimated. Therefore, I conclude that antidepressants are largely ineffective and potentially harmful.


Fouling of food process plant surfaces and the subsequent cleaning needed is a significant industrial problem, and as the cost of water and chemical disposal increases, the problem is becoming more significant. Current literature on water-based cleaning is reviewed here according to the classification of 3 types of cleaning problems. By doing this, it is hoped that new knowledge can be highlighted applicable to improving industrial cleaning. (i) For type 1 deposits (that can be cleaned with water alone)—Cleaning time appears related to Reynolds number and surface shear stress. An increase in Reynolds number seems to decrease cleaning time. Cleaning temperatures greater than 50 °C do not appear beneficial. (ii) For type 2 deposits (biofilms)—Removal behavior of biofilms seems to be dependent on the microbial aging time on the surface. Keeping a material hydrated on a surface enables easier removal of it with water. a. Water rinsing: Temperature and wall shear stress have varied effects on removal. b. Chemical rinsing: Flow and temperature were seen to have the biggest effect at the start of cleaning, but contact time was more important as cleaning progressed at a given sodium hydroxide solution flow and temperature. (iii) For type 3 deposits (that require a cleaning chemical)—For specifically, protein-based systems excessive chemical forms a deposit difficult to remove. Increasing wall shear stress and temperature was most beneficial to cleaning rather than concentration. The action of temperature can reduce the use of a chemical for type 2 and type 3 soils. The findings suggest that the right combination of flow characteristics at a given temperature and concentration is crucial to achieving fast cleaning in all cases. There are a number of cleaning monitoring methods at various stages of commercialization that may be capable of monitoring bulk cleaning and cleaning at the surface. To optimize cleaning will require integration of measurement methods into the cleaning process.


Irving Janis' (1971) concept of 'groupthink', the idea that the desire for consensus overrides the realistic appraisals of alternatives and leads to poor decision making, is a staple of management and organizational behavior textbooks. Despite gaining little support in empirical studies, Janis' eight symptoms of groupthink remains a popular framework taught to budding managers. What has been forgotten, however, is that nearly 20 years before Janis' supposed invention, groupthink was created by William H Whyte, author of one of the 1950s' most influential and popular books on management. We investigate how Whyte's link to groupthink became invisible to management's history, why this matters, and how recovering Whyte's ideas can provide fresh, critical insights into people dynamics in contemporary organizations."


Figurova, M., V. Ledeck˘, S. ·tvrtina:Evaluation of Marginal Microgaps of Two Glassionomer Cements (GIC) in Dogs and Sheep in vivo. Acta Vet. Brno 2006, 75: 403-410. The aim of the experiment was to evaluate the marginal microgaps of two ionomer cements: Kavitan Plus (Spofa Dental) and Vitremer (3M ESPE) in dog and sheep dentition in vivo. Dentitions of sheep and dogs were restored in vivo with a conventional, glass polyalkenoic, chemically activated cement Kavitan Plus with hydrophilic properties capable and with a resinmodified glass-ionomer cement Vitremer with light-induced polymerization and autopolymerization reaction of methyl metacrylate group. The parameters of glass-ionomers were evaluated in 6 groups of animals, 2 animals in each, at various time intervals (after 1, 4 and 6 months in dogs and 3, 6 and 9 months in sheep, starting from the beginning of the experiment). The restorative materials were placed to buccal surfaces of permanent teeth. At the intervals specified, under general injection anaesthesia, throughout the experiment we extracted 24 teeth from sheep and 30 from dogs. When processing the samples of dog's teeth two samples were damaged. One month after the placement, Kavitan plus restorations became loose only in one case in dogs (80% successfulness). In sheep two Kavitan Plus restorations became loose after 9 months (50% successfulness). During the experiment we observed neither cracks nor marginal discoloration in both Kavitan Plus and Vitremer restorations. Statistically significant (P = 0.04) differences were observed in the dentin of dogs receiving glass-ionomer Vitremer restorations which exhibited lower marginal microgaps. The remaining results were non- significant (ANOVA test). Fluoride ions released from GIC support the treatment of dental hard tissues. These materials could be used as definitive restorations of class A - D cavities in dogs and dental cervical caries in sheep as well as underlying layers of composite and amalgam materials. Glass-ionomer cement, experiment, dentition, incisors, premolars, histology, microgaps, restoration


The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X‐linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2‐associated retinal disorder (RP2‐RD) from four Japanese families in a nationwide cohort. A systematic review of RP2‐RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10–47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52–2.0)/1.10 (0.52–1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2‐RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement.


DFT study of the interaction of uracil, a RNA base, with Zn2+ and Cu+ ion is carried out. Most favorable sites of attachment of these ions in uracil are determined with the help of metal ion affinity (MIA) values. The two oxygen atoms of uracil are found to be the most susceptible sites of attachments of metal ions. Mulliken population analysis (MPA) method is used to determine the Mulliken charges of basic sites as well as the metal ions in all complexes. Possible correlation between the MIA and the retained charges of metal ions is thoroughly explored. Energies of frontier orbitals (HOMO and LUMO) also correlate with the MIA values.


PURPOSE/OBJECTIVES
To describe the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients with cancer to potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy.

DATA SOURCES
Published articles, abstracts, and conference proceedings.

DATA SYNTHESIS
Genetic deficiencies in DPD, the rate-limiting enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with cancer putting them at increased risk for unusually severe adverse reactions (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by specialized laboratory tests. The principle treatment for DPD-deficient patients with severe acute 5-FU reactions is supportive care; however, the administration of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such as encephalopathy and coma.

CONCLUSIONS
Early recognition of this serious pharmacogenetic syndrome may allow for the modification of future chemotherapy, thus avoiding further life-threatening toxicities.

IMPLICATIONS FOR NURSING PRACTICE
Nurses must understand the pharmacology, mechanism of action, clinical presentation, potentially lethal risks, and traumatic psychosocial stresses experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order to develop timely interventions and alternative plans of care.


The correlation between the agitation speed and the morphological changes occurred in the fungal hyphae during the production of tannase in a submerged fermentation system has been studied. Under optimal agitation speed, loose fungal pellet formation favored enzyme production. Based on the SEM and TEM studies, it was found that there were significant correlations between the speed of agitation and the hyphal morphology including its internal structures, and the activity of enzyme production. This could be due to the excessive cell permeability related to abrasion by shear forces and also by oxygen limitation.