pinecone/core-2020-05-10-deduplication huggingface dataset:
Cultivation strategies to enhance productivity of Pichia pastoris: A review

AbstractPichia pastoris, a methylotrophic yeast, is an established system for the production of heterologous proteins, particularly biopharmaceuticals and industrial enzymes. To maximise and optimise the production of recombinant products, recent molecular research has focused on numerous issues including the design of expression vectors, optimisation of gene copy number, co-expression of secretory proteins such as chaperones, engineering of glycosylation and secretory pathways, etc. However, the physiological effects of different cultivation strategies are often difficult to separate from the molecular effects of the gene construct (e.g., cellular stress through over-expression or incorrect post-translational processing). Hence, overall system optimisation is difficult, even though it is urgently required in order to describe and understand the behaviour of new molecular constructs. This review focuses on particular aspects of recombinant protein production related to variations in biomass growth and their implications for strain design and screening, as well as on the concept of rational comparisons between cultivation systems for the development of specific production processes in bioreactors. The relationship between specific formation rates of secreted recombinant proteins, qp, and specific growth rates, μ, has been analysed in a conceptual attempt to compare different systems, particularly those based on AOX1/methanol and GAP/glucose, and this has now evolved into a pivotal concept for bioprocess engineering of P. pastoris
Brownian Dynamics Simulation of DNA Condensation

AbstractDNA condensation observed in vitro with the addition of polyvalent counterions is due to intermolecular attractive forces. We introduce a quantitative model of these forces in a Brownian dynamics simulation in addition to a standard mean-field Poisson-Boltzmann repulsion. The comparison of a theoretical value of the effective diameter calculated from the second virial coefficient in cylindrical geometry with some experimental results allows a quantitative evaluation of the one-parameter attractive potential. We show afterward that with a sufficient concentration of divalent salt (typically ∼20mM MgCl2), supercoiled DNA adopts a collapsed form where opposing segments of interwound regions present zones of lateral contact. However, under the same conditions the same plasmid without torsional stress does not collapse. The condensed molecules present coexisting open and collapsed plectonemic regions. Furthermore, simulations show that circular DNA in 50% methanol solutions with 20mM MgCl2 aggregates without the requirement of torsional energy. This confirms known experimental results. Finally, a simulated DNA molecule confined in a box of variable size also presents some local collapsed zones in 20mM MgCl2 above a critical concentration of the DNA. Conformational entropy reduction obtained either by supercoiling or by confinement seems thus to play a crucial role in all forms of condensation of DNA
A charcoal-rich horizon at Ø69, Greenland: evidence for vegetation burning during the Norse landnám?

AbstractIt is often assumed that the colonisation of Greenland by Norse settlers in c. A.D. 985 had a sudden and dramatic effect on the environment, involving substantial vegetation clearance and environmental degradation. Consequently, it has been argued that charcoal-rich horizons, visible in many sections in Greenland, represent the initial burning of the vegetation by Norse farmers to create land suitable for agriculture. In this study a charcoal-rich layer, visible in a modern drainage ditch beside the Norse farm of Ø69, was analysed using archaeobotany, sedimentary analysis and radiocarbon dating to test the date and formation processes of the horizon. It is demonstrated that the charcoal-rich layer at Ø69 was not derived from in situ vegetation burning in the 10th century and concluded that the layer was probably formed by the addition of midden material to the infields around Ø69 in the 13th and 14th centuries cal AD, perhaps as part of a soil amendment strategy. It is argued that caution must be exercised when interpreting charcoal-rich horizons as time-specific chronological markers in palaeoenvironmental sequences in Greenland
Renormalization of the Cabibbo–Kobayashi–Maskawa matrix in standard model

AbstractWe have investigated the present renormalization prescriptions of Cabibbo–Kobayashi–Maskawa (CKM) matrix, and found there is still not an integrated prescription to all loop levels in the on-shell renormalization scheme. In this Letter we attempt proposing a new prescription designed for all loop levels in the present perturbative theory. This new prescription will keep the unitarity of the CKM matrix and make the amplitude of an arbitrary physical process involving quark mixing convergent and gauge independent
MicroRNA-155 Is Required for Effector CD8+ T Cell Responses to Virus Infection and Cancer

SummaryMicroRNAs (miRNAs) regulate the function of several immune cells, but their role in promoting CD8+ T cell immunity remains unknown. Here we report that miRNA-155 is required for CD8+ T cell responses to both virus and cancer. In the absence of miRNA-155, accumulation of effector CD8+ T cells was severely reduced during acute and chronic viral infections and control of virus replication was impaired. Similarly, Mir155−/− CD8+ T cells were ineffective at controlling tumor growth, whereas miRNA-155 overexpression enhanced the antitumor response. miRNA-155 deficiency resulted in accumulation of suppressor of cytokine signaling-1 (SOCS-1) causing defective cytokine signaling through STAT5. Consistently, enforced expression of SOCS-1 in CD8+ T cells phenocopied the miRNA-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miRNA-155 and its target SOCS-1 as key regulators of effector CD8+ T cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer
The application of a novel fluidised photo reactor under UV–Visible and natural solar irradiation in the photocatalytic generation of hydrogen

AbstractWith advancements in the development of visible light responsive catalysts for H2 production frequently being reported, photocatalytic water splitting has become an attractive method as a potential ‘solar fuel generator’. The development of novel photo reactors which can enhance the potential of such catalyst, however, is rarely reported. This is particularly important as many reactor configurations are mass transport limited, which in turn limits the efficiency of more effective photocatalysts in larger scale applications. This paper describes the performance of a novel fluidised photo reactor for the production of H2 over two catalysts under UV–Visible light and natural solar illumination. Catalysts Pt-C3N4 and NaTaO3·La were dispersed in the reactor and the rate of H2 was determined by GC-TCD analysis of the gas headspace. The unit was an annular reactor constructed from stainless steel 316 and quartz glass with a propeller located in the base to control fluidisation of powder catalysts. Reactor properties such as propeller rotational speed were found to enhance the photo activity of the system through the elimination of mass transport limitations and increasing light penetration. The optimum conditions for H2 evolution were found to be a propeller rotational speed of 1035rpm and 144W of UV–Visible irradiation, which produced a rate of 89μmolh−1g−1 over Pt-C3N4. Solar irradiation was provided by the George Ellery Hale Solar Telescope, located at the California Institute of Technology
R&D and productivity in OECD firms and industries: A hierarchical meta-regression analysis

AbstractThe relationship between R&D investment and firm/industry productivity has been investigated widely following seminal contributions by Zvi Griliches and others from late 1970s onwards. We aim to provide a systematic synthesis of the evidence, using 1253 estimates from 65 primary studies that adopt the so-called primal approach. In line with prior reviews, we report that the average elasticity and rate-of-return estimates are positive. In contrast to prior reviews, however, we report that: (i) the estimates are smaller and more heterogeneous than what has been reported before; (ii) residual heterogeneity remains high among firm-level estimates even after controlling for moderating factors; (iii) firm-level rates of return and within-industry social returns to R&D are small and do not differ significantly despite theoretical predictions of higher social returns; and (iv) the informational content of both elasticity and rate-of-return estimates needs to be interpreted cautiously. We conclude by highlighting the implications of these findings for future research and evidence-based policy
Tax competition and the international distribution of firm ownership : an invariance result

How does the international distribution of firm ownership affect the outcomes of tax/subsidy competition for mobile plants? As corporate ownership becomes increasingly globalised, this question becomes increasingly important for policy. We prove a strong invariance result in the context of the tax/subsidy competition between two host countries for a monopoly firm's plant. Both the equilibrium plant location and the equilibrium tax/subsidy offers are independent of the international distribution of the firm's ownership. The reason is that the tax/subsidy competition equalises the firm's post-tax profits across countries, making owners of capital indifferent towards the location of production
Decision-Theoretic Planning with Generalized First Order Decision Diagrams

This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/artificial-intelligence/.Many tasks in AI require representation and manipulation of complex functions. First-Order Decision Diagrams (FODD) are a compact knowledge representation expressing functions over relational structures. They represent numerical functions that, when constrained to the Boolean range, use only existential quantification. Previous work has developed a set of operations for composition and for removing redundancies in FODDs, thus keeping them compact, and showed how to successfully employ FODDs for solving large-scale stochastic planning problems through the formalism of relational Markov decision processes (RMDP). In this paper, we introduce several new ideas enhancing the applicability of FODDs. More specifically, we first introduce Generalized FODDs (GFODD) and composition operations for them, generalizing FODDs to arbitrary quantification. Second, we develop a novel approach for reducing (G)FODDs using model checking. This yields – for the first time – a reduction that maximally reduces the diagram for the FODD case and provides a sound reduction procedure for GFODDs. Finally we show how GFODDs can be used in principle to solve RMDPs with arbitrary quantification, and develop a complete solution for the case where the reward function is specified using an arbitrary number of existential quantifiers followed by an arbitrary number of universal quantifiers
Educational accountability tests, social and legal inclusion approaches to discrimination for students with disability : a national case study from Australia

The UN Convention on the Rights of Persons with Disability (CRPD) promotes equal and full participation by children in education. Equity of educational access for all students, including students with disability, free from discrimination, is the first stated national goal of Australian education (MCEETYA 2008). Australian federal disability discrimination law, the Disability Discrimination Act 1992 (DDA), follows the Convention, with the federal Disability Standards for Education 2005 (DSE) enacting specific requirements for education. This article discusses equity of processes for inclusion of students with disability in Australian educational accountability testing, including international tests in which many countries participate. The conclusion drawn is that equitable inclusion of students with disability in current Australian educational accountability testing in not occurring from a social perspective and is not in principle compliant with law. However, given the reluctance of courts to intervene in education matters and the uncertainty of an outcome in any court consideration, the discussion shows that equitable inclusion in accountability systems is available through policy change rather than expensive, and possibly unsuccessful, legal challenges
Development and validation of the emotion and mood components of Anxiety Questionnaire

Mood and emotion research in sport psychology is typically conducted using single adjective
checklists such as the Profile of Mood States. A limitation of single adjective
checklists is that they assess the intensity of the affective response but not the context, and
thus cannot reliably distinguish mood from emotion. Recent research has emphasized the
importance of distinguishing mood from emotion both theoretically (Lane & Terry, 2000) and
practically (Jones, 2003).The purpose of the present research was to develop a self-report measure that distinguishes mood from emotion. No such method currently exists, despite an extensive
literature attesting to theoretical distinctions between the two (see Ekman & Davidson, 1994). Beedie, Lane and Terry (2001) proposed that mood and emotion can be
distinguished empirically. Their proposal was made on the basis of content analyses of 65
published papers addressing distinctions between emotion and mood, and of interview data
from 106 participants relating to the same question (Beedie, Terry, & Lane, in press). The
present study reports the development and validation of the measure: The Emotion and Mood
Components of Anxiety Questionnaire (EMCA-Q)
Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer : results from a prospective cohort study.

background:  The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis.\ud
methods:  Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage.\ud
results:  A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, ‘feeling different’ and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit.\ud
conclusions:  Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities
An optimization model for a monopolistic firm serving an environmentally conscious market : use of chemical reaction optimization algorithm.

This work considers a monopolist firm which faces the following twin challenges of serving an environmentally sensitive market. The first challenge is the demand׳s elasticity to emissions and price. To entice its emission conscious customers and generate higher demand, the firm incrementally invests in cleaner production technologies. It also adopts a voluntary limit on its emissions from transportation. However, such investments and penalty lead to the second challenge of reduced net profit. To address above trade-off, a Non-Linear Programming (NLP) model with a maximization quadratic profit function has been formulated. Recently developed, Chemical Reaction Optimization algorithm, with superior computational performance, has been adopted to solve the NLP. The output of the model provides near optimal monopolistic price, best attainable reduction in manufacturing emissions through proportional investment and makes a choice of suitable mode of transportation for each type of product offered by the firm. Three types of sensitivity analyses were performed by varying contextual parameters: customers׳ emission elasticity, penalty charged per unit emission and investment coefficient. The results, underpin the importance of investments in cleaner technologies and the need of financial aids for profit maximizing firms operating in cleaner markets. This work provides a decision making tool to determine the near optimal degree of each of the above dimension in multiple business fronts
Neuroticism, extraversion, goals, and subjective well-being: Exploring the relations in young, middle-aged, and older adults

The positive association between intrinsic, as opposed to extrinsic, goal importance and Subjective Well- Being (SWB) is well-documented. However, less is known whether these associations are consistent across age groups and when simultaneously considering personality traits. Structural equation models conducted with young, middle-aged, and older adults indicated that neuroticism was negatively related to SWB across age groups, while extraversion and intrinsic goal importance held age-differential associ- ations: Extraversion was related to SWB in the two younger age groups, whereas in older adults only an indirect effect emerged via intrinsic goal importance. Intrinsic goal importance was related to SWB among young and older adults but not among middle-aged adults. These results underscore the impor- tance of age-differential associations in determinants of SWB
Biofuel production on wastelands in India: opportunities and trade-offs for soil and water management at the watershed scale\ud

Biofuel production from feedstocks grown on wastelands is considered a means of addressing concerns\ud
about climate change and improving energy security while at the same time providing an additional source of income\ud
for the land users. The establishment of biomass plantations on wastelands is likely to affect local livelihoods and\ud
can affect surrounding ecosystems by infl uencing hydrologic fl ows and processes such as erosion. We present an\ud
assessment of Jatropha plantation establishment on wastelands, using the ArcSWAT modeling tool. The assessment\ud
was made for a wasteland located in the Velchal watershed, Andhra Pradesh, India, which recently was converted to\ud
a biofuel plantation with Jatropha. The previous land use, in this case grazing, could continue in the Jatropha plantations.\ud
Several desirable effects occurred as a result of the land-use conversion: non-productive soil evaporation was\ud
reduced as a larger share of the rainfall was channeled to productive plant transpiration and groundwater recharge,\ud
and at the same time a more stable (less erosive) runoff resulted in reduced soil erosion and improved downstream\ud
water conditions. A win-win situation between improved land productivity and soil carbon content was observed\ud
for the Jatropha plantations. On the other hand, the results indicate that at the sub-basin scale, reductions in runoff\ud
generation as a result of large-scale conversion of wastelands to Jatropha cropping may pose problems to downstream\ud
water users and ecosystems. From a livelihoods perspective, Jatropha production was generally positive, creating a complementary source of income to the farmers, thus strengthening the resilience of the local community.\ud
In the future, the potential gain from Jatropha cropping is expected to increase as cropping systems improve and\ud
growing biofuel markets result in better conditions for biofuel producers
Neutral modes of a two-dimensional vortex and their link to persistent cat's eyes

Copyright © 2008 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Fluids 20 (2008) and may be found at http://link.aip.org/link/?PHFLE6/20/027101/1This paper considers the relaxation of a smooth two-dimensional vortex to axisymmetry after the application of an instantaneous, weak external strain field. In this limit the disturbance decays exponentially in time at a rate that is linked to a pole of the associated linear inviscid problem (known as a Landau pole). As a model of a typical vortex distribution that can give rise to cat's eyes, here distributions are examined that have a basic Gaussian shape but whose profiles have been artificially flattened about some radius rc. A numerical study of the Landau poles for this family of vortices shows that as rc is varied so the decay rate of the disturbance moves smoothly between poles as the decay rates of two Landau poles cross. Cat's eyes that occur in the nonlinear evolution of a vortex lead to an axisymmetric azimuthally averaged profile with an annulus of approximately uniform vorticity, rather like the artificially flattened profiles investigated. Based on the stability of such profiles it is found that finite thickness cat's eyes can persist (i.e., the mean profile has a neutral mode) at two distinct radii, and in the limit of a thin flattened region the result that vanishingly thin cat's eyes only persist at a single radius is recovered. The decay of nonaxisymmetric perturbations to these flattened profiles for larger times is investigated and a comparison made with the result for a Gaussian profile
Activation of invariant natural killer T cells stimulated with microbial α-mannosyl glycolipids.

Supplementary information accompanies this paper at doi:10.1038/s41598-017-10309-xSome synthetic and bacterial glycolipids presented by CD1d specifically activate invariant NKT (iNKT) cells bearing an invariant Vα14-Jα18 (mouse) or Vα24-Jα18 (human) TCR. The antigenic glycolipids identified to date consist of two hydrophobic chains and an α-glycoside in which the 2′-OH group is in the cis orientation toward the anomeric group, namely, either an α-galactoside or an α-glucoside. Several microbial α-mannosyl glycolipids, in which the 2′-OH group is in the trans orientation, were herein examined to establish whether they have potential to activate iNKT cells. We found that α-mannnosyl1-3 (6′-O-acyl α-mannosyl)-1-1 monoacylglycerol and cholesteryl 6′-O-acyl α-mannoside, found in Saccharopolyspora and Candida albicans, respectively, induced the activation of iNKT cells, dependent on CD1d. In contrast, α-mannosyldiacylglycerol found in Streptococcus suis or α-mannosylceramide demonstrated markedly less antigenicity for iNKT cells. The potentially antigenic α-mannosyl glycolipids contributed to the protection of mice against infection with S. pneumoniae in which iNKT cells have previously been found to participate. Furthermore, these glycolipids induced the production of proinflammatory cytokines by macrophages, thereby suggesting their recognition by specific pattern recognition receptors (PRRs). Collectively, these results suggest that these microbial α-mannosyl glycolipids are capable of being recognized by both the invariant TCR and PRRs and inducing immune responses.This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 20570146).Peer-reviewedPublisher Versio