The yeast Saccharomyces cerevisiae has widely been used as a host for the production of heterologous proteins. High-level production of heterologous proteins is likely to impose a metabolic burden on the host cell and can thus affect various aspects of cellular physiology. Different target proteins often do not result in similar secretion yields, underlining the dependency of secretion efficiency on the physicochemical properties of the protein of interest. Two human insulin analogue precursors (IAPs) were used as model secretory proteins. The IAPs had minor differences in their amino acid sequences, yet pictured more than 7-fold difference in their secretion yields. Global transcriptome analysis carried out in aerobic glucose-limited chemostat experiments pinpointed distinct steps during the protein maturation pathway to be differentially regulated, and indicated an increased degradation of the IAP with the low secretion yield. The use of auxotrophic strains for improved IAP production was examined. The incremental truncation of the promoter of the auxotrophic marker gene URA3 led to higher plasmid copy numbers, and illustrated that the modification of the level of the recombinant gene dosage via the degree of promoter truncation can be a strong tool for optimizing the IAP productivity. The dynamic character of adaptive responses of S. cerevisiae towards a change in their nutrient access was studied based on global gene expression analysis, scrutinizing the impact of restricted supply of phosphate on the physiological state of IAP-expressing cells. The gradual decrease of the phosphate supply resulted in a step-wise modulated phenotypic response, thereby alternating the specific productivity and the secretory flux. A data-driven approach was applied to study the secretory IAP production in S. cerevisiae in prolonged chemostat cultures (80 generations), with the aim to explore the metabolic adaptation of the cells towards the burden of IAP production. Time-course analysis of global transcriptome and targeted metabolome analysis indicated at metabolic re-modeling of the recombinant cells based on augmented negative selection pressure on glycolytic overcapacity, changes in amino acid and central carbon metabolism, and mitochondrial dysfunction to account for decreased cellular expression efficiency in long-term chemostat cultures.


Importance: Due to the evolving variants of coronavirus disease 2019 (COVID-19), it is important to understand the relationship between the disease condition and socioeconomic, demographic, and health indicators across regions. Background: Studies examining the relationships between infectious disease and socioeconomic variables are not yet well established. Design: A total of 3042 counties in the United States are included as the observation unit in the study. Two outcome variables employed in the study are the control of disease spread and infection prevalence rates in each county. Method: Data are submitted to quantile regression, hierarchical regression, and random forest analyses to understand the extent to which health outcomes are affected by demographics, socioeconomics, and health indicators. Results: Counties with better control of the disease spread tend to have lower infection rates, and vice versa. When measuring different outcome variables, the common risk factors for COVID-19 with a 5% level of statistical significance include employment ratio, female labor ratio, young population ratio, and residents' average health risk factors, while protective factors include land size, housing value, travel time to work, female population ratio, and ratio of residents who identify themselves as mixed race. Conclusions: The implications of the findings are that the ability to maintain social distancing and personal hygiene habits are crucial in deterring disease transmission and lowering incidence rates, especially in the early stage of disease formation. Relevant authorities should identify preventive factors and take early actions to fight infectious diseases in the future.


In the framework of DustBot European project, aimed at developing a new multi-robot system for urban hygiene management, we have developed a twowheeled robot: DustCart. DustCart aims at providing a solution to door-to-door garbage collection: the robot, called by a user, navigates autonomously to his/her house; collects the garbage from the user and discharges it in an apposite area. An additional feature of DustCart is the capability to monitor the air pollution by means of an on board Air Monitoring Module (AMM). The AMM integrates sensors to monitor several atmospheric pollutants, such as carbon monoxide (CO), particular matter (PM10), nitrogen dioxide (NO2), ozone (O3) plus temperature (T) and relative humidity (rHu). An Ambient Intelligence platform (AmI) manages the robots' operations through a wireless connection. AmI is able to collect measurements taken by different robots and to process them to create a pollution distribution map. In this paper we describe the DustCart robot system, focusing on the AMM and on the process of creating the pollutant distribution maps. We report results of experiments of one DustCart robot moving in urban scenarios and producing gas distribution maps using the Kernel DM+V algorithm. These experiments can be considered as one of the first attempts to use robots as mobile monitoring devices that can complement the traditional fixed stations.


Some properties of bacteriophage phi T isolated from the vaccine strain Bordetella pertussis Tohama phase I and propagated in Bordetella parapertussis 504 cells are presented. Phage phi T belongs to the IV group in accordance with Tikhonenko classification. The diameter of head and length of noncontractile tail sheath are 49.5 +/- 0.5 and 145 +/- 7 nm, respectively. Diameter of the tail sheath is 3.2 +/- 0.6 nm. Molecular mass of the phage DNA is 37 +/- 3 kb. Population of phi T phage is polymorphous and consists of particles the genomes or which vary from each other by the "insert" located 6.8 +/- 0.6 kb from the end of molecule. The blot hybridization has demonstrated that the bacteriophage genome is not inserted into the chromosome of the lysogenic strain. Autonomous location of the phage genome in the host cell is suggested. The temperature and hydrogen ions concentration effects on bacteriophage phi T stability were studied. The conditions for phage suspension storage are described.


AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), Department of Transportation (DOT). ACTION: Response to appeals. SUMMARY: On May 8, 2015, the Pipeline and Hazardous Materials Safety Administration, in coordination with the Federal Railroad Administration (FRA), published a final rule entitled ''Hazardous Materials: Enhanced Tank Car Standards and Operational Controls for High-Hazard Flammable Trains,'' which adopted requirements designed to reduce the consequences and, in some instances, reduce the probability of accidents involving trains transporting large quantities of Class 3 flammable liquids. The Hazardous Materials Regulations provide a person the opportunity to appeal a PHMSA action, including a final rule. PHMSA received six appeals regarding the final rule, one of which was withdrawn. This document responds to the five remaining appeals submitted by the Dangerous Goods Advisory Council (DGAC), American Chemistry Council (ACC), Association of American Railroads (AAR), American Fuel & Petrochemical Manufacturers (AFPM), and jointly the Umatilla, Yakama, Warm Springs, and Nez Perce tribes (Columbia River Treaty Tribes) and the Quinault Indian Nation (Northwest Treaty Tribes).


The widespread use of "Big Data" is heavily impacting organizations and individuals for which these data are collected. Sophisticated data science techniques aim to extract as much value from data as possible. Powerful mixtures of Big Data and analytics are rapidly changing the way we do business, socialize, conduct research, and govern society. Big Data is considered as the "new oil" and data science aims to transform this into new forms of "energy": insights, diagnostics, predictions, and automated decisions. However, the process of transforming "new oil" (data) into "new energy" (analytics) may negatively impact citizens, patients, customers, and employees. Systematic discrimination based on data, invasions of privacy, non-transparent life-changing decisions, and inaccurate conclusions illustrate that data science techniques may lead to new forms of "pollution". We use the term "Green Data Science" for technological solutions that enable individuals, organizations and society to reap the benefits from the widespread availability of data while ensuring fairness, confidentiality, accuracy, and transparency. To illustrate the scientific challenges related to "Green Data Science", we focus on process mining as a concrete example. Recent breakthroughs in process mining resulted in powerful techniques to discover the real processes, to detect deviations from normative process models, and to analyze bottlenecks and waste. Therefore, this paper poses the question: How to benefit from process mining while avoiding "pollutions" related to unfairness, undesired disclosures, inaccuracies, and non-transparency?


Lapp is one of the French IN2P3 labs located in Annecy-le-Vieux. In this presentation, we will explain how we moved our tape backup system from a local infrastructure to a centralized one. We were using Networker (Legato) software for more than ten years with a small LTO2 library and we switched to a mutualized infrastructure powered by CC IN2P3 using Tivoli (IBM) software. This talk will describe the new infrastructure (based on information provided by our CC-IN2P3 colleagues) and then we will detail the different steps for this migration including the integration with GPFS. We will point out the difficulties we met, the impacts on our organization and infrastructure and our future plans. On the other hand, we will also report the CC-IN2P3 point of view as a service provider.


The reversible cyclability of Si based composite anodes is greatly improved by optimizing the atomic ratio of Si/Cu, the thickness and the evaporation rates of films fabricated by electron beam deposition method. The galvanostatic test results show that 500 nm thick flim, having 10%at. Cu-90%at. Si, deposited with a moderate evaporation rate (10 and 0.9 Å/s for Si and Cu respectively) delivers 2642.37 mAh g(-1) as the first discharge capacity with 76% Coulombic efficiency. 99% of its initial capacity is retained after 20 cycles. The electron conductive pathway and high mechanical tolerance induced by Cu atoms, the low electrical resistivity of the film due to Cu3Si particles, and the homogeneously distributed nano-sized/amorphous particles in the composite thin film could explain this outstanding electrochemical performance of the anode.


Thermal scanning probe lithography (t-SPL) has demonstrated unique capabilities for maskless lithography. A heated atomic force microscope tip is used to locally remove a thermally sensitive resist. This process is able to fabricate precise 3D patterns and high resolution structures without the use of charged particles, such as electrons, which have been implicated in substrate damage. Here we outline our work to improve the throughput of t-SPL via integration with a laser writer for the patterning of large features and the development of independently addressable cantilever arrays.


The objective of this article is the design and implementation of wideband RF power amplifiers that can be used in different solid-state wireless transmitting systems. A systematic technique has been devised and confirmed. This technique uses the RF power transistor's optimum load and source impedances, obtained from the load-pull procedure, to characterize the RF power device at the required output power level and operating frequency band. The input and output device impedances are taken as the complex conjugates of the optimum source and load terminations and are stored in external data files as one-port networks. The input and output matching networks can then be optimized separately, using a suitable microwave circuit optimization program, to achieve the required matching between the stored impedance data and the terminal 50-Omega impedances across the frequency band of interest. The microwave CAD program Touchstone has been utilized to implement this technique. As a practical implementation to the proposed design procedure, a 1-W class-C power amplifier circuit was designed and built to operate within the communication band 225-400 MHz and to achieve a power gain of 10-dB


Using data for the period 1991 - 2004, this study investigates the strategic priorities of senior management in provincial Russia. The study is based on interviews with top management in twenty former state owned provincial companies and a number of external respondents. It analyses managerial decision making patterns during the transition and post-transition periods. A strong tendency for Russian provincial managers to pursue operational restructuring with a very little attention to strategic planning was identified. We also argue that managerial attitude toward strategic decision making appears to be a key success factor of large national projects of strategic importance.
As there was a lack of prior studies in this geographical area and a general bias towards areas with a high economic activity index, this study employed a phenomenological approach to study strategic managerial priorities and presents qualitative data which enriches understanding of enterprise transformation in the Russian province.

Data gathered during the study demonstrate how managerial priorities relate to the Russian companies' transformational patterns. The study identified a number of pivotal areas which were prioritised by Russian directors as crisis-management strategies. The study suggests that the primary objectives of the top managers in provincial Russia are based around preserving production level, employees, status quo, and personal benefits. The data suggest that in the given underdeveloped institutional environment managers often use corporate objectives for their own benefit. This paper also suggests that an authoritarian model of enterprise management and autarky can be an effective mechanism to combat serious problems of transitional instability.


We investigated the role of moral disengagement in a legally-relevant judgment in this theoretically-driven empirical analysis. Moral disengagement is a social-cognitive phenomenon through which people reason their way toward harming others, presenting a useful framework for investigating legal judgments that often result in harming individuals for the good of society. We tested the role of moral disengagement in forensic psychologists' willingness to conduct the most ethically questionable clinical task in the criminal justice system: competence for execution evaluations. Our hypothesis that moral disengagement would function as mediator of participants' existing attitudes and their judgments—a theoretical "bridge" between attitudes and judgments—was robustly supported. Moral disengagement was key to understanding how psychologists decide to engage in competence for execution evaluations. We describe in detail the moral disengagement measure we used, including exploratory and confirmatory factor analyses across two separate samples. The four-factor measure accounted for a total of 52.18 percent of the variance in the sample of forensic psychologists, and the model adequately fit the data in the entirely different sample of jurors in a confirmatory factor analysis. Despite the psychometric strengths of this moral disengagement measure, we describe the pros and cons of existing measures of moral disengagement. We outline future directions for moral disengagement research, especially in legal contexts.


Among the first 111 patients with renal masses examined by ultrasound most renal cysts (98%) and carcinomas (86%) were correctly detected. Diagnostic accuracy was high when ultrasound predicted a renal cyst (97%), but renal carcinoma accounted for only 60% of the complex echo masses found. Ultrasound was used as the primary, non-invasive test for the selection of outpatients with simple renal cysts for diagnostic puncture and for the selection of those with complex renal masses for more elaborate and expensive inpatient investigation. Ultrasound is not infallible but a safe diagnostic pathway may be drawn up in which ultrasound errors are not allowed to lead to diagnostic disasters. This approach reduced the use of arteriography for renal masses by two-thirds. With care the diagnosis of the common chance finding of a renal mass can be made simpler, safer, and cheaper.


Background: As the South African economy continues to grow, the role of small and medium-sized enterprises (SMEs) as a potential source for employment creation and productivity within the country has become widely acknowledged. However, one area in which the SMEs in the country still need to develop is in their implementation of supply chain management practices, particularly their relationships with suppliers, which could result in either the failure or success of any business enterprise. Majority of studies conducted in this area have focussed on large firms, thereby creating a research gap in this area. Aim: The aim of this study was to examine the influence of supplier integration on supply chain performance in South African SMEs. Setting: This study was conducted in Gauteng province of South Africa. Methods: A quantitative research methodology was employed in this study. A convenient sample comprising 283 owners and managers from SMEs drawn from the Gauteng Province was used in the study. The collected data were then analysed using Pearson's correlation and regression analysis. Results: Positive correlations were found between supplier integration and both the tangible and intangible sub-dimensions of supply chain performance. Supplier integration also predicted both the tangible and intangible sub-dimensions of supply chain performance. Conclusion: These results imply that to improve the performance of their supply chains, it is imperative for SMEs to ensure that linkages with their suppliers are properly aligned for improved coordination, which leads to better relationships and supply of materials. This study contributes to the literature by proposing and testing the influence of supplier integration on supply chain performance.


Utilization of membrane offers the promise of huge energy savings if successfully applied to petroleum separations. Membranes are bound to enter into refining petroleum operations involving liquid separations once appropriate materials and modules are developed. Hybrid processes such as utilizing membrane modules to azeotropes formed during distillation are particularly attractive because they can offer less process complexity and reduced capital investment. A pervaporation performance was studied using pervaporation through the polymer blendmembranes for the separation of benzene and cyclohexane mixtures to investigate the relationship between pervaporation performance and polymer blend design. Solubility parameter calculation and thermodynamic calculation were used to predict the pervaporation performance for the benzene and cyclohexane mixture system using polymeric blend membrane composed of NBR, PVC and polar copolymers with various solubility parameters. The solubility parameter of the polymer blend membranes were controlled with different blend ratio. Screening of the membranes was accomplished by simple swelling experiments. Selectivity for the polar component increased with increasing NBR and PVC contents. Solubility parameter from polar and hydrogen bonding properties and activity calculated from thermodynamic model predicted the trend of swelling characteristics and pervaporation performance. Solubility parameter and thermodynamic calculation provide an a priori methodology for seeking the best blend formulations.


We thank Knobloch et al for their comments about the development and validation of the URAM scale for Dupuytren's disease. The URAM scale is indeed a tool to assess patient-reported functional outcome in Dupuytren's disease and we agree that assessing disability is of key importance in Dupuytren's disease. However, we would like to respond to a few points made by Knobloch et al. We emphasize that the validation of a scale for a specific condition has to be done in the disease being considered and not another disease. Specificity here is a question of what disease from which the scale has been developed and in which it has been validated, and of functional limitation due to the considered condition; it is not only a question of side (right hand or left hand). Validation means studying the reliability, the construct validity, and the responsiveness as has been done for the URAM scale. To our knowledge, neither the DASH nor the MHQ have been validated in such a way for Dupuytren's disease. Our opinion is that nonvalidated scales should not be recommended and used to assess disability in Dupuytren's disease. Nonetheless, we are grateful to Knobloch et al for their German translation of the URAM scale. We compliment them for using the French language version and translating it into the German language version using sound methodology. We encourage using the URAM scale in patients with Dupuytren's disease, including German patients. Indeed, assessment of the disease should not be limited to the flexion contracture. A patient's subjective perception of their own difficulties in daily living is pertinent in current practice and recommended in clinical trials (1,2). The URAM scale is the only scale developed and validated to assess disability in Dupuytren's disease. Therefore, the URAM scale should be part of the assessment of Dupuytren's disease in current practice and in future clinical trials. Finally, we agree with Knobloch et al that the recurrence rate is also of key importance for assessing effectiveness of treatments in Dupuytren's disease and that a consensus definition of recurrence is needed. Several definitions have previously been proposed and used, including reappearance of cords, nodules, or contracture requiring further operation with followup of a few months to several years (3). A consensus definition of recurrence should therefore include the criteria for recurrence and the time of its assessment.


The equations of three‐dimensional linear acoustics are formulated using a complex state vector and a first‐order Lagrangian. Local conservation equations for energy, linear momentum, and angular momentum are derived in a unified and systematic way from gauge transformations. The first‐order Lagrangian description is shown to lead naturally to a set of discrete space and discrete time field equations. Gauge transformations are again used to derive local conservation equations for the discrete field variables. Dispersion relations for the discrete equations are derived, and are used to analyze the spatial isotropy of propagating waves on the discrete space‐time lattice. The solution of the discrete initial value problem is discussed, as well as its implementation on a massively parallel computer.


The Regge-Wheeler equation describes the axial perturbations of Schwarzschild metric in linear approximation. We present its exact solutions in terms of the confluent Heun's functions, the basic properties of the general solution, novel analytical approach and numerical techniques for study of different boundary problems which correspond to quasi-normal modes of black holes and other simple models of compact objects. We depict in more detail the exact solutions of Regge-Wheeler equation in the Schwarzschild black hole interior and on Kruscal-Szekeres manifold.


This paper proposes an error-driven HMM-based text chunk tagger with context-dependent lexicon. Compared with standard HMM-based tagger, this tagger incorporates more contextual information into a lexical entry. Moreover, an error-driven learning approach is adopted to decrease the memory requirement by keeping only positive lexical entries and makes it possible to further incorporate more context-dependent lexical entries. Finally, memory-based learning is adopted to further improve the performance of the chunk tagger.


In the years 2000 - 2011 (12 years) was conducted weed survey on the farms in conventional farming system. The goal was to detect the most harmful weeds, as important biotic, environmental stress factor, on the farms in the canopies of pea for grain in maize, sugar beet and potato production regions of the Slovak Republic. The fields were selected in all production regions of Slovakia. An actual weed infestation was evaluated before preemergence application of herbicides. Screening of each field was made on 1 m 2 area with four replications. The four randomly established sample quadrants were situated minimally 20 m from field margin and apart from each other, respectively. The level of infestation was evaluated according to average density of weeds per square meter. Obtained data from farms was statistically analyzed by correlation analysis in Statistica 7.0. In the pea for grain canopies 10 most dangerous weed species were detected, the most problematic were: perennial weeds Cirsium arvense (L.) Scop. and Elytrigia repens (L.) DESV and annual weeds Atriplex spp., Avena fatua L., Amaranthus spp., Anthemis spp., Chenopodium spp., Tripleurospermum perforatum (Merat) M. Lainz, Echinochloa crus galli (L.) P. Beauv and Datura stramonium (L.). Temporal dynamic of actual weed infestation depends on production region. After herbicides control the significant changes in weed flora were noted in term of abundance and share of some weed species on total weed community. Temporal dynamics of actual weed infestation depend on climate conditions of maize, sugar beet and potato production region, forecrop and pea stand health condition. Spring and perennial weeds are always a problem in pea for grain stands, because pea plants are not so competitive, but control may be considered necessary to safeguard crop quality and yield. The originality of result is in mapping the weed species and its actual weed infestation in cultural crops (pea for grain stands).


The DNA of higher eukaryotes contains small quantities of the minor base B-methylcytosine, formed by enzymatic transfer of methyl groups from S-adenosyl-L-methionine (SAM) to cytosine residues on polymeric DNA. The function of this methylated base is uncertain. In order to examine the mechanism and specificity of methylation, DNA methylase has been purified some 400-fold from Krebs II ascites tumour cells. This enzyme preparation has the following properties: (1) There is no evidence for more than one enzyme species. (2) The only product of methylation by the enzyme is 5-methylcytosine in DNA. Methylation is absolutely dependent on added substrate DNA. (3) The enzyme methylates DNA from a variety of animal, cultured cell and bacterial sources, but at widely differing rates. Higher rates of in vitro methylation are generally observed with DNAs from rapidly dividing cells. C4) Several experiments on the mechanism of action of the enzyme indicate that it operates by a series of repeated transient binding events at different sites in the DNA, rather than by an initial binding at a specific site follov/ed by a linear traverse of the DNA helix. (5) The enzyme can methylate both native and denatured calf thymus DNA; in E.coli DNA, however, only single-stranded regions are methylated even in a "native" DNA preparation. This could be caused by the enzyme requiring hemimethylated sites in double-stranded DNA, which are presumably absent from E. coli DNA. (6) Methylation of denatured DNA by the enzyme shows a strikingly greater resistance to inhibition by salt than does methylation of native DNA. The explanation suggested for this is that native and denatured DNA are methylated by different forms of the enzyme, perhaps by a dimer and a monomer respectively. This is based on the results of gel filtration and density gradient centrifugation, which show that under high salt conditions the enzyme exists as a smaller species than at low salt. Although not precisely determined, the approximate molecular weights of these species are consistent with the larger being a dimer of the smaller, which has a molecular weight of about 160,000.


REPORT OF A CASE In January 1987, a 38-year-old man presented to another institution with a several-month history of pruritus, night sweats, and an enlarged left axillary node. He had been diagnosed with stage IIB nodular sclerosing Hodgkin's disease and was treated with radiation to the upper mandible with resolution of his night sweats and a decrease in his pruritus. However, at the completion of his radiation therapy, papules and nodules developed on the patient's forehead and scalp. A skin biopsy specimen obtained at another institution reportedly showed follicular mucinosis with dermal and subcutaneous eosinophilia. The patient was treated with minocycline (100 mg orally twice a day) with little improvement. In January 1988, the patient was referred to the Department of Dermatology, MetroHealth Medical Center, Cleveland, Ohio, when new eroded papules and plaques developed on the left preauricular and postauricular areas (Fig 1). He received no therapy except minocycline and had no


CONTEXT
In the meadow of medical sciences substituting a diseased organ with a healthy one from another individual, dead or alive, to allow a human to stay alive could be consider as the most string event. In this article we review the history of transplantation, mechanisms of rejection, nephro-neurotoxicity of tacrolimus and cyclosporin in organ transplantations.

EVIDENCE ACQUISITIONS
Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched.

RESULTS
The first reference to the concept of organ transplantation and replacement for therapeutic purposes appears to be to Hua-To (136 to 208 A.D), who replaced diseased organs with healthy ones in patients under analgesia induced with a mixture of Indian hemp. In 1936, the first human renal transplant performed by Voronoy in Russia. The first liver transplant in humans was performed on March 1, 1963 by Starzl in Denver, USA. Medawar was the first to assert that rejection was an immunological response, with the inflammatory reaction due to lymphocyte infiltration. Consequently, rational immunosuppressive therapies could inhibit deleterious T-cell responses in an antigen specific manner.

CONCLUSIONS
Searching related to the history of organ transplantation from mythic to modern times suggests that, to prevent graft rejection, minimize nephro and neuro toxicity monitoring of immunosupressive concentrations could provide an invaluable and essential aid in adjusting dosage to ensure adequate immunosuppression.


Analysis of antibiotic-resistant EF-Tu mutants has revealed a connection between resistance and structural elements that participate in the GTPase switching mechanism. Both random and site-directed mutagenesis methods have yielded sets of purified mutant EF-Tu resistant to kirromycin (kirT) or pulvomycin (pulT). All kirT mutations cluster in the interface of domain 1 and 3 of EF-Tu in its GTP-bound conformation, not in that of EF-Tu.GDP. Other evidence also suggests that kirromycin binds to the interface of wild-type EF-Tu, thereby jamming the GTPase switch. Various functional studies reveal two subsequent resistance mechanisms. The first hinders kirromycin binding to EF-Tu.GTP and the second occurs after GTP hydrolysis by rejection of bound kirromycin. All pulT mutations cluster in the three-domain junction interface of EF-Tu. GTP (which is an open hole in EF-Tu.GDP) and destabilize a salt-bridge network. Pulvomycin may bind nearby and overlap with tRNA binding. Mutations show that a D99-R230 salt bridge is not essential for the transduction of the GTPase switch signal from domain 1. In vivo and in vitro studies reveal that pulvomycin sensitivity is dominant over resistance. This demands a revision of the current view of the mechanism of pulvomycin inhibition of protein synthesis and may support a translation model with two EF-Tus on the ribosome. Several mutant EF-Tu species display altered behaviour towards aminoacyl-tRNA with interesting effects on translational accuracy. KirT EF-Tu(A375T) is able to reverse the streptomycin-dependent phenotype of a ribosomal protein S12 mutant strain to streptomycin sensitivity.


The intramolecular cyclisation of 2-hydroxyphenylacetic acid 1 into coumaran-2-one 2 was studied under both microwave irradiation and classical heating for comparison purposes. The use of a monomode oven allowed an accurate consideration of the temperature distribution in the microwave reaction vessel, which revealed a very strong and unexpected thermal heterogeneity. The reaction was facilitated by the presence of a trace of toluene-p-sulfonic acid, the catalytic role of which is demonstrated.


We have isolated a high molecular weight compound from tobacco callus (Nicotiana tabacum) that is active in lowering intraocular pressure (IOP) when injected intravenously into rabbits. Extracts were made from 2‐week‐old callus and from callus maintained in culture for varying amounts of time. Extracts of new callus were tested for IOP‐lowering activity and analysed for carbohydrate, protein, amino acid composition, and uronic acid content. Initial studies showed these extracts to be very active, lowering IOP almost to the maximum at doses of 200 μg. Partial characterization of the crude extract indicated that it contained 22% protein, 12% neutral sugar, and 5% uronic acid by weight. Extracts from callus maintained in culture for 2 months showed marginal activity when tested at 200 μg per animal. The material was fractionated by gel permeation chromatography on Fractogel TSK HW 65F. Fractions from chromatography were analysed for neutral sugar, protein, neutral sugar composition, and uronic acid content. The composition of the active material resembles plant cell wall components of the pectic type.


In April 2017, several scale insect specimens in the family Dactylopiidae were collected from infested cladodes of wild Opuntia tomentosa Salm-Dyck, 1822 (Cactaceae) in the outskirts of Morelia City, Michoacan, Mexico. The specimens were identified as Dactylopius confusus (Cockerell, 1929) (Hemiptera: Coccomorpha: Dactylopiidae). In this article, the presence of D. confusus in Michoacan state, Mexico, is recorded for the first time. A subsequent finding of D. confusus on Opuntia ficus-indica (L.) Mill., (1768) (Cactaceae) in October 2019 was confirmed with 18S rDNA and 28S rDNA.


To optimize Nb/Al-AlO/sub x//Nb Josephson junctions, atomic force microscopy is used to study the morphology of DC magnetron-sputtered Nb and Al. The Nb film stress was sensitive to Ar pressure, and changed from compressive to tensile as the Ar pressure increased. The roughness of DC magnetron-sputtered Nb films was related to their internal stress. Stress-free Nb films have a smooth surface, without depressions, and a roughness of 14.6 AA. The roughness of the Al surface on Nb film was shown to reflect the roughness of the underlying Nb film, and was least for the stress-free Nb film. Coverage of Al was continuous for Al thicker than 40 AA. To make a fine Nb/Al-AlO/sub x//Nb Josephson junction, one should use a stress-free Nb film and deposit an Al layer at least 40 AA thick on the Nb films.<<ETX>>


In Colombia, diabetes mellitus is a public health program for those responsible for creating and implementing strategies for prevention, diagnosis, treatment, and follow-up that are applicable at all care levels, with the objective of establishing early and sustained control of diabetes. A clinical practice guide has been developed following the broad outline of the methodological guide from the Ministry of Health and Social Welfare, with the aim of systematically gathering scientific evidence and formulating recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The current document presents in summary form the results of this process, including the recommendations and the considerations taken into account in formulating them. In general terms, what is proposed here is a screening process using the Finnish Diabetes Risk Score questionnaire adapted to the Colombian population, which enables early diagnosis of the illness, and an algorithm for determining initial treatment that can be generalized to most patients with diabetes mellitus type 2 and that is simple to apply in a primary care context. In addition, several recommendations have been made to scale up pharmacological treatment in those patients that do not achieve the objectives or fail to maintain them during initial treatment. These recommendations also take into account the evolution of weight and the individualization of glycemic control goals for special populations. Finally, recommendations have been made for opportune detection of micro- and macrovascular complications of diabetes.


When a criminal defendant who is not competent to stand trial refuses to take voluntarily the antipsychotic medications that might make him become competent, should the government be allowed to administer the medications involuntarily? Increasingly, trial courts are answering "yes." Since the Supreme Court's 2003 decision in Sell v. United States, trial courts have almost routinely approved the administration of involuntary antipsychotic medications for the purpose of rendering criminal defendants competent to stand trial. Although most courts acknowledge that antipsychotic medications can cause serious, even life-threatening side effects, this article argues that the test set forth in Sell does not require courts to take adequate account of the potential physical harms of involuntary antipsychotic medications. This fault with the Sell test can be traced back to its roots, as a due process test, in decisions primarily concerned with protecting an individual's interest in making autonomous choices, not with protecting an individual's interest in avoiding physical harms. This article compares the Sell due process test to the Fourth Amendment test that courts apply when the government seeks to compel involuntary medical treatment for the purpose of obtaining evidence of a crime from a criminal defendant's body. In these cases, the medical treatment must be reasonable - that is, the government's interest that is advanced by the involuntary treatment must be important enough to justify the potential physical harms to the defendant. This article concludes that because Sell does not require courts to balance the government's interest in rendering a defendant competent to stand trial against the physical harms that the defendant is likely to experience if administered involuntary antipsychotic medications, the Sell test inadequately protects incompetent criminal defendants from physical harms that are unreasonable.


Background The Global Burden of Diseases, Injuries, and Risk Factors Study, 2010 was established to provide reliable estimates on the leading causes of death and morbidity in populations worldwide and how these are changing over time. The aim of this paper is to present the findings of the study in relation to road injury in order to inform policy debates in the area of road safety. Methods Information on death and morbidity was obtained from various sources (vital registration, verbal autopsy, surveillance, censuses, surveys, hospitals, police records, etc.) for 187 countries. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). YLLs were calculated from age-sex-country-time-specific estimates of mortality and death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of disabling sequelae, by age, sex, and cause; and weighted by new disability weights. Results The number of deaths related to road injury increased by 43.6% from 908,000 in 1990 to 1.329 million in 2010.This rise was mainly due to pedestrians deaths which increased by 62.3% from 284,000 in 1990 to 461,000 in 2010. Road injury was the leading cause of death among males aged 15–49 years in 2010. Road injury moved from being the 14th cause of YLL globally in 1990 to 8th in 2010. In term of DALYs, road injury also moved from 12th position in 1990 to 10th in 2010. Regional analysis shows road deaths in east Asia, south Asia, and eastern and western sub-Saharan Africa rapidly escalating over the past two decades, whereas in high-income areas with a history of road safety programmes such as western Europe, high-income North America, Australia and New Zealand road deaths have decreased. Conclusions Despite various global road safety initiatives, the burden from road injury globally continues to rise, particulary amongst pedestrians. Continued efforts from all sectors are needed in order to address this growing challenge. *List of all collaborators (a few hundreds) and their affiliations will be provided as part of the presentation at the conference, if the abstract is accepted.


The resonant tunneling diode (RTD) has found numerous applications in high-speed digital and analog circuits due to the key advantages associated with its folded back negative differential resistance (NDR) current-voltage (I-V) characteristics as well as its extremely small switching capacitance. Recently, the RTD has also been employed to implement high-speed and compact cellular neural/nonlinear networks (CNNs) by exploiting its quantum tunneling induced nonlinearity and symmetrical I-V characteristics for both positive and negative voltages applied across the anode and cathode terminals of the RTD. This paper proposes an RTD-based CNN architecture and investigates its operation through driving-point-plot analysis, stability and settling time study, and circuit simulation. Full-array simulation of a 128 times 128 RTD-based CNN for several image processing functions is performed using the Quantum Spice simulator designed at the University of Michigan, where the RTD is represented in SPICE simulator by a physics based model derived by solving Schrodinger's and Poisson's equations self-consistently. A comparative study between different CNN implementations reveals that the RTD-based CNN can be designed superior to conventional CMOS technologies in terms of integration density, operating speed, and functionality.


In some real world applications, acquiring covariates for classification can be cost-intensive and should be limited as much as possible. For example, in the medical setting, a doctor cannot just perform all possible types of tests to classify whether the patient has diabetes or not. The decision of classifying or acquiring more covariates before classifying is dependent on the costs of new covariates and the expected optimal cost of misclassification (Bayes risk). However, estimating the latter is a formidable task due to the estimation of a high dimensional probability density and intractable integrals.
In this work, we show that for linear classifiers this task can be considerably simplified, leading to a one dimensional integral for which we propose an efficient approximation. Experimental results on three datasets show consistent improvements over previously proposed methods for cost-sensitive classification. We also demonstrate that our proposed Bayes risk estimation procedure can benefit from additional unlabeled data which can be helpful when only small amount of labeled data is available.


Elicitation of cell suspension cultures of Capsicum assamicum (Bhut Jolokia) for enhancement of capsaicin content was tried using different elicitors such as cellulase, vanillin, methyl jasmonate, salicylic acid and sinapic acid in different concentrations for 24, 48 and 72 hours. Cell suspension culture was established in B5 media supplemented with 3.5 mM 2,4-D (2,4-diphenoxyacetic acid) and 1.1 mM Kin and elicitors were introduced at the end of exponential phase. All the elicitors, except methyl jasmonate, led to significant increase in production of capsaicin. Sinapic acid, when added in 22 µM concentration and incubated for 24 hours, led to highest capsaicin accumulation of 0.5% (5068 µg/g) which was highest among all the treatments.


Loxoscelism is often misdiagnosed, in part because the clinical presentation of loxoscelism is similar to that of other conditions, such as cutaneous anthrax and Lyme erythema migrans (EM). Differentiating these disorders is important because some of these conditions require early treatment to achieve the best clinical outcomes. Unfortunately, using geography to make or exclude a diagnosis is becoming less reliable.


Background: Atopic dermatitis has a characteristic clinical manifestation and flexural distribution of lichenified eczematous plaques. Clinical manifestations and treatment of atopic dermatitis have been studied vigorously. However, Korean studies on clinical manifestation have mainly focused on predilection sites, and no study was performed about lesional difference in the severity and reactivity to treatment. Objective: The aim of this study is to primarily determine the difference in lesional predilection and lesional severity of atopic dermatitis. Second objective is to compare lesional reactivity to treatment with topical tacrolimus 0.1% ointment. Methods: Authors mapped the patients` dermatitis lesions by dividing human body parts at the first visit. Then, topical tacrolimus 0.1% ointment was applied to one side of the body and humectants were applied to the other side of body. In order to evaluate the reactivity to the treatment, transepidermal water loss, pH, and skin surface hydration were measured. Results: The frequency of involvement of wrist and ankle, as well as well-known predilection site, was high in children. More than half of the wrist and ankle lesions were grouped as severe. Although tacrolimus was superior to simple emolients in most lesions, reactivity to the treatment was low in wrist and ankle. Conclusion: The wrist and ankle, as well as other predilection sites were frequently involved with significant severity, and showed low reactivity to the treatment. These areas need to be carefully evaluated and treated. Dermatitis mapping might be helpful in clinical evaluation and management by visualization of lesions and changes.


7-Thiabicyclo[4.3.0]non-3-ene 7,7-dioxide 3 and the 2,5-bridged analogues 4–6 formed by Diels–Alder reaction of 2,3-dihydrothiophene 1,1-dioxide (2-sulfolene)2 with butadiene and cyclic 1,3-dienes are found, upon flash vacuum pyrolysis, either to lose SO2 and ethene, or to undergo a retro-Diels–Alder reaction, depending on the degree of ring strain present. The epoxides 10, 13 and 17 of these compounds decompose exclusively by loss of SO2 and ethene to give the mono-epoxides of cyclic 1,4-dienes which undergo further reactions under the pyrolysis conditions. The same final products can also be obtained by extrusion of CO and CO2 from the epoxides 12, 16 and 19 of the corresponding diene–maleic anhydride adducts. In the case of the furan–maleic anhydride adduct, its epoxide 20 fragments by a retro-Diels–Alder reaction to give 1,4-dioxine, which, at high temperatures, is transformed into acrylaldehyde. Pyrolysis of the aziridines 22–24, formed by photochemical reaction of the diene–maleic anhydride adducts with ethyl azidoformate, generally gives complex decomposition products, although for the methylene-bridged compound 22 there is good evidence for the generation of a 1,4-dihydropyridine via a retro-Diels–Alder reaction.


Although the extant literature has much research on location-based targeting, it does not distinguish between inside and outside a location. This paper extends the literature by considering mobile coupons issued outside and inside the location in the setting of a shopping mall with multiple stores, where each store may issue mobile in-app coupons to potential customers. We first empirically examine the effect of coupons on stores' sales using a proprietary dataset from a large Chinese shopping mall. We show a stronger sales effect of coupon clicks made by consumers outside the mall than inside the mall, implying a trafficconversion effect – bringing additional traffic to the mall – that has been overlooked in prior literature. Our data also suggest that stores may not gain more sales from issuing coupons, but can benefit from free-riding on other stores' coupons. Motivated by our empirical findings, we build a mathematical model to investigate optimal location-based coupon strategy. Our analytical results identify the conditions regarding whether and where a store selling experiential or functional products should issue coupons, which not only echo our empirical findings, but also show that without distinguishing inside or outside a location, marketers may underestimate these coupon effects and may target the wrong consumers. Lastly, we show the existence of the prisoner's dilemma where stores would not offer coupons, although they would be better off issuing coupons; moreover, we show that the driver is the coupons' traffic-conversion effect. This underscores the needs for mall owners to coordinate marketers in making coupon decisions.


Background The integration of graphene in photovoltaic modules, fuel cells, batteries, supercapacitors, and devices for hydrogen generation offers opportunities to tackle challenges driven by the increasing global energy demand. Graphene's two-dimensional (2D) nature leads to a theoretical surface-to-mass ratio of ~2600 m2/g, which combined with its high electrical conductivity and flexibility, gives it the potential to store electric charge, ions, or hydrogen. Other 2D crystals, such as transition metal chalcogenides (TMDs) and transition metal oxides, are also promising and are now gaining increasing attention for energy applications. The advantage of using such 2D crystals is linked to the possibility of creating and designing layered artificial structures with "on-demand" properties by means of spin-on processes, or layer-by-layer assembly. This approach exploits the availability of materials with metallic, semiconducting, and insulating properties. Advances The success of graphene and related materials (GRMs) for energy applications crucially depends on the development and optimization of production methods. High-volume liquid-phase exfoliation is being developed for a wide variety of layered materials. This technique is being optimized to control the flake size and to increase the edge-to-surface ratio, which is crucial for optimizing electrode performance in fuel cells and batteries. Micro- or nanocrystal or flake edge control can also be achieved through chemical synthesis. This is an ideal route for functionalization, in order to improve storage capacity. Large-area growth via chemical vapor deposition (CVD) has been demonstrated, producing material with high structural and electronic quality for the preparation of transparent conducting electrodes for displays and touch-screens, and is being evaluated for photovoltaic applications. CVD growth of other multicomponent layered materials is less mature and needs further development. Although many transfer techniques have been developed successfully, further improvement of high-volume manufacturing and transfer processes for multilayered heterostructures is needed. In this context, layer-by-layer assembly may enable the realization of devices with on-demand properties for targeted applications, such as photovoltaic devices in which photon absorption in TMDs is combined with charge transport in graphene. Outlook Substantial progress has been made on the preparation of GRMs at the laboratory level. However, cost-effective production of GRMs on an industrial scale is needed to create the future energy value chain. Applications that could benefit the most from GRMs include flexible electronics, batteries with efficient anodes and cathodes, supercapacitors with high energy density, and solar cells. The realization of GRMs with specific transport and insulating properties on demand is an important goal. Additional energy applications of GRMs comprise water splitting and hydrogen production. As an example, the edges of MoS2 single layers can oxidize fuels—such as hydrogen, methanol, and ethanol—in fuel cells, and GRM membranes can be used in fuel cells to improve proton exchange. Functionalized graphene can be exploited for water splitting and hydrogen production. Flexible and wearable devices and membranes incorporating GRMs can also generate electricity from motion, as well as from water and gas flows. Tailored GRMs for energy applications. The ability to produce GRMs with desired specific properties paves the way to their integration in a variety of energy devices. Solution processing and chemical vapor deposition are the ideal means to produce thin films that can be used as electrodes in energy devices (such as solar panels, batteries, fuel cells, or in hydrogen storage). Chemical synthesis is an attractive route to produce "active" elements in solar cell or thermoelectric devices. Graphene and related two-dimensional crystals and hybrid systems showcase several key properties that can address emerging energy needs, in particular for the ever growing market of portable and wearable energy conversion and storage devices. Graphene's flexibility, large surface area, and chemical stability, combined with its excellent electrical and thermal conductivity, make it promising as a catalyst in fuel and dye-sensitized solar cells. Chemically functionalized graphene can also improve storage and diffusion of ionic species and electric charge in batteries and supercapacitors. Two-dimensional crystals provide optoelectronic and photocatalytic properties complementing those of graphene, enabling the realization of ultrathin-film photovoltaic devices or systems for hydrogen production. Here, we review the use of graphene and related materials for energy conversion and storage, outlining the roadmap for future applications. Layered materials power the cause Methods for storing and converting energy, including fuel cells, solar cells, and water splitting, often benefit from having materials with a large surface area. When combined with a high surface reactivity, high conductivity, or useful optical properties, two-dimensional layered materials become of notable interest for a range of applications. Bonaccorso et al. review the progress that has been made using graphene and other layered or two-dimensional materials at laboratory scales and the challenges in producing these materials in industrially relevant quantities. Science, this issue 10.1126/science.1246501


Abstract Terrestrial laser scanning (TLS) can be used to either complement or replace traditional methods of characterizing both the geometry and structural geology of unstable slopes. TLS data collected from a failed bedrock slope threatening the main east–west highway in the Bhutan Himalaya are presented and interrogated for structural information. The structural data, along with TLS-derived slope geometry and cross-sectional profiles, are suitable for use within commercially available slope stability packages to derive solutions for the causes of instability, likely geometry of failure, and future activity under varied scenarios. The methods also allow the possibility of future model verification and calibration though TLS monitoring. The results of TLS-based numerical modelling utilizing a commercially available code are presented and the implications for slope surveying, numerical modelling, monitoring and management are discussed.


13%Cr stainless steel has good comprehensive performance, which makes it suitable to work under the condition of high temperature, high pressure and corrosive environment, such as petroleum industry. It can be used as materials of petroleum pipes with buttress thread. Buttress thread turning is a heavy-load machining, which places high requirement on the cutting tool. Based on the cutting characteristics of buttress thread, the machinability of 13%Cr stainless steel is studied by turning experiments. Two kinds of inserts with different geometries were employed in buttress thread turning experiments. Experimental results show that less cutting force, longer tool life, better chip curling effect and surface quality was acquired for the insert with rake angle of 12° , clearance angle of 3° and chip-curling groove during 13%Cr stainless steel buttress thread turning process.


The pathogenesis of the male pseudohermaphroditism in the mouse with X-linked testicular feminization (Tfm) has been investigated by comparing testosterone formation, the effects of androgen administration, and the metabolism of testosterone-1,2-(3)H in normal mice and Tfm mice of varying ages. First, it was established that the adult Tfm animal, in contrast to the human with testicular feminization, has both a low serum testosterone and a low rate of testosterone formation as assessed in slices of testes utilizing a variety of precursors. However, the formation of testosterone from pregnenolone-7alpha-(3)H was shown to be normal in newborn Tfm testes, suggesting that a defect in testosterone synthesis may not be primary to this mutation. Second, to establish that the pseudohermaphroditic state is due to androgen resistance rather than to diminished androgen biosynthesis during fetal life, the effect of the administration of dihydrotestosterone to pregnant animals was studied in male, female, and Tfm offspring. Whereas normal and carrier female littermates demonstrated striking virilization of the internal genital tract after such treatment, there was no sign of virilization in the Tfm animals. This finding provides direct experimental evidence in support of the view that male pseudohermaphroditism in testicular feminization is the result of resistance to androgen action during androgen-mediated sexual differentiation in embryos. Third, the metabolism of testosterone-1,2-(3)H was investigated both in tissue slices and in functionally hepatectomized animals. Dihydrotestosterone formation in tissue slices of the fetal anlage of the male organs of accessory reproduction is normal in the Tfm animal, suggesting that the primary defect in this disorder involves an intracellular event subsequent to this step and that the deficient dihydrotestosterone formation observed in the adult genital tract of the Tfm mouse is secondary to the failure of differentiation in these tissues. Finally, deficient binding of testosterone in the nuclei of the submandibular gland of adult Tfm animals, a known testosterone target tissue, was demonstrated in functionally hepatectomized mice. This finding could either be a manifestation of the primary genetic defect in this disorder or might reflect another acquired abnormality due to incomplete differentiation of adrogen-sensitive cell lines.


Modulation caused by surface/subsurface contaminants is one of the important factors for laser-induced damage of fused silica. In this work, a three-dimensional finite-difference time-domain (3D-FDTD) method is employed to simulate the electric field intensity distribution in the vicinity of particulate contaminants on fused silica surface. The simulated results reveal that the contaminant on both the input and output surfaces plays an important role in the electric field modulation of the incident laser. The influences of the shape, size, embedded depth, dielectric constant (εr), and the number of contaminant particles on the electric field distribution are discussed in detail. Meanwhile, the corresponding physical mechanism is analyzed theoretically.


Prolyl endopeptidase (PREP), probably acting through the inositol cycle, has been implicated in memory and learning. However, the physiological role of PREP is unknown. It has been shown that PREP expression, regulated in cerebellar granule cells, has probably a role in cell proliferation and differentiation. Here, we report the levels and subcellular distribution of PREP in human neuroblastoma SH-SY5Y cells in proliferating conditions and under differentiation induced by retinoic acid (RA). We analysed the levels of cell signalling intermediates, growth behavior and gene expression, and differentiation morphology changes, upon PREP inhibition. After induction of differentiation, PREP activity was found decreased in the nucleus but increased to high levels in the cytoplasm, due in part to increased PREP transcription. The levels of inositol (1,4,5)-trisphosphate revealed no correlation with PREP activity, but phosphorylated extracellular signal-regulated kinases 1 and 2 were decreased by PREP inhibition during early stages of differentiation. Morphological evaluation indicated that PREP inhibition retarded the onset of differentiation. PREP activity regulated gene expression of protein synthesis machinery, intracellular transport and kinase complexes. We conclude that PREP is a regulatory target and a regulatory element in cell signalling. This is the first report of a direct influence of a cell signalling molecule, RA, on PREP expression.


Summary.  Current ecotoxicological risk assessment for chemical substances is based on the assumption that tolerances of all species in a specified ecological community are a priori exchangeable for each new substance. We demonstrate non‐exchangeability by using a large database of tolerances to pesticides for fish species and extend the standard statistical model for species tolerances to allow for the presence of a single species which is considered non‐exchangeable with others. We show how to estimate parameters and adjust decision rules that are used in ecotoxicological risk management. Effects of parameter uncertainty are explored and our model is compared with a previously published less tractable alternative. We conclude that the model and decision rules that we propose are pragmatic compromises between conflicting needs for more realistic modelling and for straightforwardly applicable decision rules.


The response of the respiratory apparatus to CO2 during acute oxygen want was investigated in anesthetized dogs. The ratio of elevated ventilation to unit increase of PaCOCO2 in hypoxia to that in normoxia (SR) was taken as a measure of interaction between hypoxia and hypercapnia. Furthermore, the separate effect on ventilation by PaCOCO2 (DeltaAVR/DeltaPco2) and \[H+\] (DeltaAVR/DeltaH) during hypoxic hypercapnia was evaluated. a) SR increased in the presence of mild anoxia (80–50 mm Hg of PaOO2), then decreased in severe anoxia (less than 50 mm Hg of PaOO2). b) DeltaAVR/DeltaPco2 showed a higher value than the normoxia level in mild hypoxia (80–55 mm Hg of PaOO2), then progressively decreased with a further development of anoxia. c) DeltaAVR/DeltaH started increasing at about 70 mm Hg of PaOO2, then increased as the PaOO2 decreased, and reached about four times the normal at 30–40 mm Hg of PaOO2. The marked difference between isolated Pco2 and [H+] effect on ventilation in severe hypoxia suggested different areas and actions in the respiratory system of both chemical agents.

separate effect of [H+] and Pco2 on ventilation

Submitted on September 3, 1964


A novel silicon controlled rectifier (SCR) with high holding voltage (Vh) for electrostatic discharge (ESD) protection is proposed and investigated in this paper. The proposed SCR obtains high Vh by adding a long N+ layer (LN+) and a long P+ layer (LP+), which divide the conventional low voltage trigger silicon controlled rectifier (LVTSCR) into two SCRs (SCR1: P+/Nwell/Pwell/N+ and SCR2: P+/LN+/LP+/N+) with a shared emitter. Under the low ESD current (IESD), the two SCRs are turned on at the same time to induce the first snapback with high Vh (Vh1). As the IESD increases, the SCR2 will be turned off because of its low current gain. Therefore, the IESD will flow through the longer SCR1 path, bypassing SCR2, which induces the second snapback with high Vh (Vh2). The anti-latch-up ability of the proposed SCR for ESD protection is proved by a dynamic TLP-like (Transmission Line Pulse-like) simulation. An optimized Vh2 of 7.4 V with a maximum failure current (It2) of 14.7 mA/μm is obtained by the simulation.


RationaleOrgan- or tissue-specific antigens produced by normal tissue or by cancer cells could be used in cancer immunotherapy, to target the tumor. In our previous study, we induced T-cell-mediated, bladderspecific autoimmunity by targeting the bladder-specific protein Uroplakin 3A (UPK3A). UPK3A is a well-chosen target for developing an autoimmune response against bladder cancer since the antigen is also expressed in bladder tumors. To use this peptide, which was derived from the UPK3A protein in a bladder cancer vaccine study, it is necessary to induce a strong immune response. In this study, we aimed to develop a robust immune response in BALB/c mice using the well-characterized keyhole limpet hemocyanin (KLH)-conjugated peptide antigen (UPK3A 65-84) conjugated with an immunogenic carrier protein. In combination with the peptide, we used either Freund's complete adjuvant (CFA) or CpG (cytosine-phosphate-guanine oligonucleotides) as effective adjuvants in order to overcome tumor tolerance.ObjectivesThe immune response evoked by UPK3A 65-84 peptide, using two different adjuvants, was compared by detection of changes in the proliferative response of immune cells, in the cytokine profile, and in the immune cell populations.FindingsWe demonstrated that CpG, combined with KLH-UPK3A 65-84, promoted a more robust immune response, via induction of higher IL-2, IFN-γ, TNF-α, IL-17 production and activation of more immune cells (CD4+ T cells, CD8+ T cells, NK cells CD11b, CD45), than CFA and the KLHUPK3A 65-84.ConclusionCpG as an adjuvant combined with KLH-UPK3A 65-84 could be used in preclinical models of bladder cancer for the development of cancer immunotherapy strategies.


Nano-twinned structures are mechanically stronger, ductile and stable than its non-twinned form. We have investigated the effect of varying twin spacing and twin boundary width (TBW) on the yield strength of the nano-twinned copper in a probabilistic framework. An efficient surrogate modelling approach based on polynomial chaos expansion has been proposed for the analysis. Effectively utilising 15 sets of expensive molecular dynamics simulations, thousands of outputs have been obtained corresponding to different sets of twin spacing and twin width using virtual experiments based on the surrogates. One of the major outcomes of this work is that there exists an optimal combination of twin boundary spacing and twin width until which the strength can be increased and after that critical point the nanowires weaken. This study also reveals that the yield strength of nano-twinned copper is more sensitive to TBW than twin spacing. Such robust inferences have been possible to be drawn only because of applying the surrogate modelling approach, which makes it feasible to obtain results corresponding to 40 000 combinations of different twin boundary spacing and twin width in a computationally efficient framework.


The dielectric constant, magnetic permeability, and refractive index are the fundamental optical parameters of a material. To investigate these optical parameters, a mixed-type common-path heterodyne interferometer is developed in this paper. By using this interferometer to detect the amplitudes and phases of both the transmission and reflection coefficients, the complex dielectric constant, magnetic permeability, and refractive index can be obtained using the algorithm discussed here. The validity of the mixed-type common-path heterodyne interferometer is demonstrated for visible lights, such as red, green, and blue, using lasers as light sources. Furthermore, the specifications for characterizing the optical properties of samples using the mixed-type common-path heterodyne interferometer are investigated. For example, dielectric constant epsiv, magnetic permeability mu, and the refractive index n of 2.161 + i0.002, 0.9997 - i0.0009, and 1.4699 - i3.4 times10-7 with low uncertainties of 0.003 + i0.002, 0.0003 + i0.0009, and 0.0007 + i8 times10-8, respectively, for a fused quartz measuring 632.8 nm are investigated. It also demonstrated that, in the case of the investigation in visible ranges, the measurement procedure is performed by only the common-path transmission type heterodyne interferometer.


APPLIED PHYSICS
Graphene has received much recent attention, both experimental and theoretical, because of its mechanical stability and promising electronic properties. These single sheets of graphite, or unzipped carbon nanotubes, are expected to display many interesting transport properties that are dependent on geometry and crystallographic orientation, in much the same way in which the electronic properties of carbon nanotubes are dependent on their chirality, or how they are rolled up. Working with single sheets of graphene extracted from bulk graphite and patterned into strips of various widths (ranging from 10 to 100 nm) and a selection of crystallographic orientations, Han et al. have probed the ensuing transport properties. They found that the energy band gap widens with decreasing width, as expected from theory, but that there is no systematic variation with orientation. The results suggest a route to engineer the band gap of graphene nanostructures with potential applications for devices. ISO

Phys. Rev. Lett. 98 , 206805 (2007).


Women attending a dermatologic vulvar clinic were asked to reply by mail to an anonymous questionnaire asking simple questions about sexual function and pregnancy following the development of lichen sclerosus. Additional comments were invited from respondents. The majority of women of all ages reported that lichen sclerosus had a detrimental effect on sexual function, with problems including dyspareunia, apareunia and difficulty achieving orgasm. The symptoms may relate to continuing inflammatory disease as well as to anatomic changes and scarring from long-standing active disease. Disease-suppressing therapy should be instituted at the earliest opportunity, and surgery to reverse the effects of scarring should be considered.


Utility properties of forgings, particularly the mechanical ones, are among the primary aspects of interest to the customers of forge shops. These properties arise from internal structure whose evolution depends predominantly on the combination of parameters of deformation processes applied during forging, on the temperature profile during cooling and on the shape of the forged part. As microstructural evolution depends on the shape of the particular cross section of the forged part, an appreciable inhomogeneity of mechanical properties occurs in forgings. This article deals with observation of microstructural evolution in a chosen forged part, depending on cooling profiles of its various cross sections. The experimental programme of mechanical working and treatment of the forged part was based on the material-technological modelling approach. Microstructural evolution was studied using light and electron microscopic methods. Results of this analysis provided a basis for outlining optimization steps for mechanical working and treatment of the forged part.


The use of elastic bodies within a multibody simulation became more and more important within the last years. To include the elastic bodies, described as a finite element model in multibody simulations, the dimension of the system of ordinary differential equations must be reduced by projection. For this purpose, in this work, the modal reduction method, a component mode synthesis based method and a momentmatching method are used. Due to the always increasing size of the non-reduced systems, the calculation of the projection matrix leads to a large demand of computational resources and cannot be done on usual serial computers with available memory. In this paper, the model reduction software Morembs++ is presented using a parallelization concept based on the message passing interface to satisfy the need of memory and reduce the runtime of the model reduction process. Additionally, the behaviour of the Block-Krylov-Schur eigensolver, implemented in the Anasazi package of the Trilinos project, is analysed with regard to the choice of the size of the Krylov base, the blocksize and the number of blocks. Besides, an iterative solver is considered within the CMS-based method.


The lunar atmosphere is extremely tenuous compared to the Earth's atmosphere and circumlunar plasma produced by photoionization is considered to be less dense than solar wind. Nevertheless, it was reported that 500 to 1000 cm−3 electron densities were observed at altitudes of 5 to 10 km near the sunrise terminator by the Soviet Luna 19 and 22 in the 1970s. The high-density layer was interpreted to be the lunar ionosphere. This result remains controversial, however, because the observed large density is difficult to explain theoretically without magnetic shielding from the solar wind. Observation data on the circumlunar plasma were very scarce and the existence of the lunar ionosphere had been neither experimentally proved nor disproved while many researchers have tried to explain its generation mechanism. The Japanese Kaguya project provided the opportunity to diagnose the vertical extent of the circumlunar plasma through a new approach using interference patterns of natural plasma waves in addition to the conventional radio occultation experiment. Although the radio occultation technique is profoundly influenced by the earth's ionosphere, the newly-developed method can sensitively detect plasma layers regardless of the conditions of the earth's ionosphere. In the present study, using the new method, we estimated the vertical electron densities at the terminator regions and examined whether the high-density layer actually existed or not.


BACKGROUND: More options for smokers wanting to stop,
more restrictions on smoking, the introduction of
standardised packaging, and a stronger anti-smoking
culture in England all mean that it should be getting
easier for smokers to stop. This paper examines quit
success rates from 2007 to 2017 and compares rates for
the first 6 months of 2017 with those in the preceding 10
years.
METHODS: Data were collected from 18,356 participants
using cross-sectional household surveys from
representative samples of adults in England from
January 2007 to June 2017. Quit success was defined as
having tried to stop in the preceding 12 months and
reporting still not-smoking at time of the survey. Sociodemographic
information was collected on sex, age,
region in England and socioeconomic status. Odds
ratios were calculated comparing quitting in 2017 versus
2007-2016 in the full sample and interactions with
socio-demographic variables were assessed.
RESULTS: Quit success rates varied over time from a low
of 13.4% (95% CI 11.9-14.9) in 2010 to a high of 19.8%
(95% CI 16.7-22.9) in 2017. The figure for 2017 was
significantly higher than the average for the preceding
10 years (OR=1.33, 95% CI 1.09-1.62). There was no
clear evidence that the difference varied with sex, age or
region but the increase in success rates was greater in
people with lower socio-economic status (OR=1.66,
95% CI 1.11-2.51).
CONCLUSION: Quit smoking success rates in England in
the first six months of 2017 were higher than the average
rate during the preceding decade. This improvement was
exclusively in those with lower socioeconomic status.


We report the first observation of long-lived states (LLS) having lifetimes T(LLS) that exceed the corresponding spin-lattice relaxation times T(1) by more than a factor 6 in a protein. Slow diffusion coefficients characteristic of large biomolecules can be determined by combining LLS methods with moderate pulsed field gradients (PFGs) available on commercial probeheads, as the extension of spin memory reduces the strain on the duration and/or strength of the PFGs. No isotope labeling of the biomolecule is necessary.


BACKGROUND
Vulval cancer is a rare gynaecological cancer. There is no standard approach for treating locally advanced primary vulval cancer (FIGO stage III and IV). Combined treatment modalities have been developed using radiotherapy, chemotherapy and surgery. The advantages and disadvantages of such treatment is not well evaluated.

OBJECTIVES
To evaluate the effectiveness and safety of neoadjuvant and primary chemoradiation for women with locally advanced primary vulval cancer compared to other primary modalities of treatment such as primary surgery or primary radiation.

SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE (to July 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.

SELECTION CRITERIA
Randomised controlled trials (RCTs) or non-randomised studies that included multivariate analyses of chemoradiation in women with locally advanced, primary squamous cell carcinoma of the vulva.

DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data and assessed risk of bias. An adjusted hazard ratio (HR) for overall survival was calculated for one non-randomised study and risk ratios (RRs) were used in an RCT to compare five-year death rates and adverse events in women who received neoadjuvant, primary chemoradiation or primary surgery. Adverse events were also reported more extensively in a further non-randomised study. All results were displayed in single study analyses.

MAIN RESULTS
One RCT and two non-randomised studies that allowed for multivariate analyses met the inclusion criteria and included a total of 141 women.One RCT found that neoadjuvant chemoradiation did not appear to offer longer survival compared to primary surgery in advanced vulval tumours (RR = 1.29, 95% confidence interval (CI) 0.87 to 1.91). There was also no statistically significant difference in survival between primary chemoradiation and primary surgery in a study that included 63 women (pooled adjusted HR= 1.09, 95% CI 0.37 to 3.17) and in another study that only included 12 eligible women and compared the same interventions (HR was non-informative when statistical adjustment was made).Adverse events were extensively reported in only one study, which found no statistically significant difference in risk of adverse events between primary chemoradiation and primary surgery due to the very small numbers in each group. In the RCT there was no observed statistically significant difference between neoadjuvant chemoradiation and primary surgery. Adverse events were not reported in the largest study of 63 women. Quality of life (QoL) was not reported in any of the included studies. All studies were at high risk of bias.

AUTHORS' CONCLUSIONS
Women with advanced vulval tumours showed no significant difference in overall survival or treatment-related adverse events when chemoradiation (primary or neoadjuvant) was compared with primary surgery.The retrospective studies had a high risk of bias as the entry criteria for primary chemoradiation was based on inoperability or tumour requiring exenteration.The radiochemotherapy regimens varied widely. There was no data on QoL.There is no standard terminology for 'operable and inoperable vulval cancer', and for 'primary and neoadjuvant chemoradiation'. Stratification according to unresectability of the primary tumour and/or lymph nodes is needed, for good quality comparison.


The quality of processed workpieces is affected directly by the precision of the linear stage. Therefore, the linear displacement calibration of machine tools must be implemented before delivery and after employment for a period of time. How to perform a precise calibration with high inspection efficiency is a critical issue in the precision mechanical engineering industry. In this study, the self-developed system integrated by the measurement module based on the common path Fabry–Pérot interferometer for linear displacement and the auto-alignment module for optical axes was proposed to realize the automatic linear displacement calibration of the linear stages. The measurement performance of the developed structure was verified experimentally. With the auto-alignment module, the cosine error was reduced to 0.36 nm and the entire procedure accomplished within 75 s without the limitation of the perceived resolution of the human eye, operational experience, and the risk of misalignment and broken cable. According to the comparison of experimental results for the linear displacement, the repeatability of the proposed measurement module was less than 0.171 μm. After the compensation procedure according to the linear displacement calibration, the systematic positional deviation, repeatability, and accuracy of the linear axis could be improved to 4 μm, 1 μm, and 5 μm respectively. Hence, the calibration efficiency can be improved by 80% with the proposed compact system, which is beneficial for the linear displacement calibration of machine tools in the precision mechanical engineering industry.


In 1993 and early 1994, Freeport McMoRan Copper and Gold (FCX), a mining company, issued two series of gold-denominated depositary shares to raise 430 million dollars expanding their mining capacity in Indonesia. We price the depositary shares using a term structure model for the forward rates implied by gold futures and we show that FCX successfully enhanced the credit quality of the issue. This credit enhancement is achieved because the effect of linking the payoff of the depositary shares to gold reduces default risk and is similar to conventional risk management. However, the bundling of financing and risk management allows the firm to target hedging benefits only to the newly issued securities. The design of the security also overcomes the asset substitution problem. The depositary shares issued by FCX illustrate how firms can enhance credit quality through financial engineering without changing the existing priority ordering of their capital structure.


Visual anemometry (VA) leverages observations of fluid-structure interactions to infer incident flow characteristics. Recent work has demonstrated the concept of VA using both data-driven and physical modelling approaches applied to natural vegetation. These methods have not yet achieved generalization across plant species and require site-specific calibration. We conducted a laboratory study in an open circuit wind tunnel using overhead imagery of three vegetation species to assess the utility of vegetation displacement fields for wind speed inference. Both the wind and vegetation speeds exhibited a two-parameter Weibull distribution. The relationship between the scale factor (one of the two parameters) of the wind and vegetation was found to be well described by a sigmoid function, indicating three regions of distinct structural response to the wind loading at low, intermediate, and high wind speeds. Within an intermediate range of wind speeds, the wind and vegetation scale factors are nearly linearly proportional, thereby facilitating VA. Importantly, the wind and vegetation scale factors were found to be uncorrelated in low and high wind regimes, revealing a fundamental constraint on VA using structure response data. We discuss the physical basis for these regimes and present additional parametric relationships that can be exploited in the intermediate wind regime to potentially generalize inference of the wind speed and direction.


ABSTRACT This paper aims to articulate the multi-regulatory and complex territory that programme developers of professional doctorates are required to navigate, and, using examples from Health Psychology and Sport and Exercise Psychology, discusses the impact of this territory on programme development. 'Practitioner Psychologist' is a legally protected title for use by those listed on the UK's Health and Care Professions Council (HCPC) register of practitioner psychologists. Achieving registration involves undergoing training to meet the HCPC prescribed standards, with the professional practitioner doctorate representing a viable training vehicle. The paper makes critical comparison between the HCPC standard-driven research and practice competences required of psychology professionals in a professional doctorate framework, versus traditional professional doctorates that provide a platform for qualified 'in situ' professionals to undertake research that problem solves and generates real–world application. For programme developers, the paper outlines a number of key considerations, including the importance of considering the territorial compatibility between the professional body requirements and the associated university framework to develop a viable product. The paper also provides some useful and informative suggestions for programme developers who may encounter similar territorial challenges, and is of relevance to an international audience interested in programme design for certified professional practitioners.


Franchise stores employ nearly nine million people in the United States. Many franchisors, which own trademarks that they license to franchisees, are among the largest, most sophisticated corporations in the United States. Yet, franchise store employees are often paid below the minimum wage and frequently report unsafe workplaces and workplace discrimination. The thesis of this Article is that widespread employment law noncompliance in franchise stores is symptomatic of the failure of employment law to recognize the measures that franchisors use to protect their brand in franchise stores. Franchisors often develop intensive relationships with franchisees and franchise store employees as representatives of the brand, and provide franchisees with required or recommended personnel standards and business tools. These standards and tools can encourage employment law violations by triggering employment law obligations, which franchisees, who own and operate franchise stores, have little incentive to understand or follow. Yet the joint employer doctrine, which holds contractors that are joint employers jointly and severally liable for employment law violations by subcontractors, often does not recognize these measures as evidence of joint employment. Courts, accordingly, often reject joint employer claims against franchisors, even when the franchise relationship may mask or encourage employment law violations in franchise stores. Although most scholarship focuses on the joint employer doctrine to deter subcontractor employment law violations, this Article argues that improving compliance in franchise stores will require liability standards that recognize these unique features of franchising and do not depend on a joint employer determination. It identifies apparent agency and misrepresentation theories in existing law that would hold franchisors liable for employment law violations based on their representations to franchisees and franchise store employees. It offers these standards as a conceptual framework to deter employment law violations in franchise stores and evaluates potential over- and underdeterrence critiques. This analysis has important implications for the governance of contractual relationships in which a firm contracts out for employees who represent the firm's brand to the consumer.


Per- and polyfluoroalkyl substances (PFAS) are a large group of manmade chemicals that impose emerging environmental concerns. Among them, short-chain per- and polyfluorinated carboxylic acids represent an important subgroup used as building blocks of biologically active chemicals and functional materials. Some are also considered PFAS alternatives, and some could be byproducts of the physicochemical treatment of PFAS. However, little is known about the environmental fate of short-chain fluorinated carboxylic acids (FCAs) and their defluorination/transformation by microorganisms. To fill the knowledge gap, we investigated the structure-reactivity relationships in the aerobic defluorination of C3-C5 FCAs by activated sludge communities. Four structures exhibited greater than 20% defluorination, with 3,3,3-trifluoropropionic acid being almost completely defluorinated. We further analyzed the defluorination/transformation pathways and inferred the structures susceptible to aerobic microbial defluorination. We also demonstrated that the defluorination was via cometabolism. The findings advance the fundamental understanding of aerobic microbial defluorination and help assess the environmental fate of PFAS. Since some short-chain PFAS, such as 3,3,3-trifluoropropionic acid, are the incomplete defluorination byproducts of advanced reduction processes, their defluorination by activated sludge communities sheds light on the development of cost-effective chemical-biological PFAS treatment train systems.


The surfaces of airless bodies, such as the Moon and asteroids, are subject to space weathering, which alters the mineralogy of the upper tens of nanometers of grain surfaces. Atom probe tomography (APT) has the appropriate 3‐D spatial resolution and analytical sensitivity to investigate such features at the nanometer scale. Here, we demonstrate that APT can be successfully used to characterize the composition and texture of space weathering products in ilmenite from Apollo 17 sample 71501 at near‐atomic resolution. Two of the studied nanotips sampled the top surface of the space‐weathered grain, while another nanotip sampled the ilmenite at about 50 nm below the surface. These nanotips contain small nanophase Fe particles (~3 to 10 nm diameter), with these particles becoming less frequent with depth. One of the nanotips contains a sequence of space weathering products, compositional zoning, and a void space (~15 nm in diameter) which we interpret as a vesicle generated by solar wind irradiation. No noble gases were detected in this vesicle, although there is evidence for 4He elsewhere in the nanotip. This lunar soil grain exhibits the same space weathering features that have been well documented in transmission electron microscope studies of lunar and Itokawa asteroidal regolith grains.


OBJECTIVEEndovascular stent reconstruction is the primary intervention for cervical and intracranial dissections in symptomatic patients refractory to medical management. Advancement of traditional balloon-expanding stents into the distal internal carotid artery and vertebrobasilar artery can be technically challenging and potentially traumatic. METHODSOn retrospective review, nine patients at our institution with distal cervical and/or intracranial dissections were alternatively treated with the self-expanding, dedicated intracranial Neuroform stent. Three patients with dissecting aneurysms also required stent-assisted coil embolization. Seven patients were followed with imaging and clinical assessment for a mean of 16.3 months. RESULTSAll patients (five men, four women; mean age, 50 yr) were symptomatic. Spontaneous (n = 4) or traumatic and/or iatrogenic (n = 5) dissections involved the internal carotid artery (n = 2), vertebral artery (n = 5), and vertebrobasilar artery (n = 2). Indications for treatment included transient ischemic attacks, impending infarcts, antiplatelet failure, enlarging or ruptured dissecting aneurysms, intracranial dissections, or subarachnoid hemorrhages. Dissections were treated with single (n = 4), overlapping (n = 2), or tandem (n = 3) Neuroform stents. Dissection-related mean stenosis improved from 76% preprocedure to 23% postprocedure, with further reduction to 8% at follow-up imaging. Stent-assisted coil embolization of large dissecting aneurysms (n = 3) resulted in retreatment of a neck remnant (n = 1). Small dissecting aneurysms (n = 5) underwent spontaneous stent-induced thrombosis. There were no procedure-related complications. Mortality was limited to the presenting sequelae of vertebrobasilar artery thrombosis (n = 2). Suboptimal technical outcomes were related to delayed in-stent stenosis (n = 2). All surviving patients (n = 7) reported clinical improvement or resolution of symptoms. CONCLUSIONThe Neuroform stent seems to be safe and technically effective in the endovascular management of distal cervical and intracranial dissections, with favorable clinical outcomes.


Abstract Objective: Data are limited on the use of adjuvant imatinib in patients with gastrointestinal stromal tumor (GIST) outside of clinical trials. This retrospective, population-based, matched-cohort study evaluated adjuvant imatinib treatment patterns, assessed impact on clinical outcomes, and estimated effectiveness based on number needed to treat (NNT). Research design and methods: GIST-related claims from the PharMetrics claims database were included (2000–2010). A stepwise identification algorithm identified appropriate patients based on GIST-related ICD-9-CM codes, who were classified as 'imatinib (IM) patients' receiving imatinib within 84 days post-surgery and 'non-imatinib (non-IM) patients' undergoing surgery but not receiving imatinib during the study period. The primary composite outcome was based on incidence of a second GIST-related surgery and long-term follow-up in the matched cohorts. IM patients were matched with up to eight non-IM patients on age, gender, ICD-9-CM code, and first surgery date. Results: A total of 118 IM and 4088 non-IM patients with possible GIST ICD-9s and surgery were included. The median duration between first and second surgeries was significantly longer in IM than non-IM patients (488 vs. 290 days; p = 0.0005). IM patients also had longer median follow-up from initial surgery to composite outcome (433 vs. 320 days; p = 0.002). Adherence to IM, measured by medication possession ratio, was 0.83 and 0.73 during the first and second years of treatment, respectively. IM patients were less likely to have the composite outcome compared with non-IM patients (hazard ratio = 0.501; p = 0.0005). The NNT to prevent one outcome was 4. Conclusions: Patients receiving adjuvant imatinib treatment were less likely to have second surgery or be lost to follow-up, and had a longer interval to second surgery. Although treatment with adjuvant imatinib in patients with primary GIST is effective, adherence to imatinib and treatment duration are less than recommended by current treatment guidelines.


Forming of alloy and composite within a solid-liquid region, i.e. thixo-forming and rheo-forming, has been recognized as a technology offering several potential advantages over casting and forging such as a low forming pressure, reduction of macrosegregation, and reduction of porosity. In this paper, a globularization for primary solid phase by a forced fluid flow in melt due to electromagnetic stirring during solidification and isothermal stirring at solid-liquid region, was examined to produce Al alloy having a globular solid phase to get a thixotropic behavior. The electromagnetic stirrer was specially designed and manufactured to create all kind of fluid flow pattern such as a circumferential, vertical, helicoidally and contra-rotating flow pattern during the solidification of a melt. The size and roundness of primary solid phase of the quenched sample after isothermal stirring at solid-liquid region were measured with respect to a stirring time and frequency. The globularization of solid phase was enhanced with incresing the stirring time and electromagnetic flux density, i.e. stirring strength.


Background: patients prefer dry powder inhalation to nebulisation but the Colobreathe dry powder inhaler for colistimethate sodium (CMS) is not well appreciated in the Netherlands for a number of different reasons, including serious cough problems by some patients after inhalation of the drug. Aim: to assess the suitability of the Twincer as alternative to the Colobreathe for patients having problems with this capsule based inhaler. Methods: in vitro evaluation of the Twincer (55 mg) and Colobreathe (125 mg) was performed using the Next Generation Impactor and a laser diffraction apparatus (Sympatec HELOS) operated at 4 kPa (inhalation volume: 4L; n = 3). Results: laser diffraction analyses shows a finer aerosol from the Twincer than from the Colobreathe. Delivered CMS doses and fine particle doses (FPFs 1-5 µm) from Colobreathe were 126 mg (+14.7/-31.9 mg) and 25.5 mg (+2.8/-3.5 mg) respectively versus 48.5 mg (+2.9/-3.3 mg) and 26.4 mg (+1.4/-1.2 mg) from Twincer. Capsule fragmentation and emission of capsule fragments was observed during evaluation of the Colobreathe but not for the Twincer (having the drug in an aluminum blister). Conclusions: The higher dispersion efficiency of the Twincer (FPF is 54.4% of delivered dose versus 20.2% for Colobreathe) enables to inhale a much lower dose (at lower flow rate) without capsule fragments in the aerosol. As a consequence, the Twincer is expected to be better tolerated by patients and, therefore, provides a suitable alternative to the Colobreathe. This expectation is corroborated by positive feedback from the first patients suffering from CF or non-CF bronchiectasis who received the Twincer on the basis of 9medical need9.


Approximate Bayesian Gaussian process (GP) classification techniques are powerful non-parametric learning methods, similar in appearance and performance to support vector machines. Based on simple probabilistic models, they render interpretable results and can be embedded in Bayesian frameworks for model selection, feature selection, etc. In this paper, by applying the PAC-Bayesian theorem of McAllester (1999a), we prove distribution-free generalisation error bounds for a wide range of approximate Bayesian GP classification techniques. We also provide a new and much simplified proof for this powerful theorem, making use of the concept of convex duality which is a backbone of many machine learning techniques. We instantiate and test our bounds for two particular GPC techniques, including a recent sparse method which circumvents the unfavourable scaling of standard GP algorithms. As is shown in experiments on a real-world task, the bounds can be very tight for moderate training sample sizes. To the best of our knowledge, these results provide the tightest known distribution-free error bounds for approximate Bayesian GPC methods, giving a strong learning-theoretical justification for the use of these techniques.