566 research outputs found
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Platform Markets and Energy Services
A structural shift from transaction-based, marginal cost pricing to fee-based service business models often accompanies We emergence of “platform” markets, i.e. multi-sided markets where an intermediary captures the value of the interaction between user groups. The many examples include telecommunications, data storage, cinema, music and media, and the automobile industry. Why not electricity? In this paper, we explore how the electricity supply industry can be conceived of as a platform-mediated, two-sided market and the consequences for pricing. Through two cases, a balancing services provider for smart home energy management systems and an electric vehicle charge manager, we show where a platform entrant could position itself in the retail electricity markets between supply companies and end-users. The drivers of such a transition include increased volatility due to renewable generation, the new complexity of roles for end-users, and the introduction of information and communication technologies. Conceiving of electricity as a platform market where new entrants provide an energy optimisation and management service may stimulate a competitive ecosystem and innovation. We suggest that fee-based pricing would enable the objectives of time-varying pricing to be achieved without adversely affecting the most vulnerable customers
Bioinformatic analysis of the CLE signaling peptide family
Background. Plants encode a large number of leucine-rich repeat receptor-like kinases. Legumes encode several LRR-RLK linked to the process of root nodule formation, the ligands of which are unknown. To identify ligands for these receptors, we used a combination of profile hidden Markov models and position-specific iterative BLAST, allowing us to detect new members of the CLV3/ESR (CLE) protein family from publicly available sequence databases. Results. We identified 114 new members of the CLE protein family from various plant species, as well as five protein sequences containing multiple CLE domains. We were able to cluster the CLE domain proteins into 13 distinct groups based on their pairwise similarities in the primary CLE motif. In addition, we identified secondary motifs that coincide with our sequence clusters. The groupings based on the CLE motifs correlate with known biological functions of CLE signaling peptides and are analogous to groupings based on phylogenetic analysis and ectopic overexpression studies. We tested the biological function of two of the predicted CLE signaling peptides in the legume Medicago truncatula. These peptides inhibit the activity of the root apical and lateral root meristems in a manner consistent with our functional predictions based on other CLE signaling peptides clustering in the same groups. Conclusion. Our analysis provides an identification and classification of a large number of novel potential CLE signaling peptides. The additional motifs we found could lead to future discovery of recognition sites for processing peptidases as well as predictions for receptor binding specificity
Resolution of diaschisis contributes to early recovery from post-stroke aphasia
Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site. We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis. Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect. We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients
Successful switching of patients with acute schizophrenia from another antipsychotic to brexpiprazole: Comparison of clinicians\u27 choice of cross-titration schedules in a post hoc analysis of a randomized, double-blind, maintenance treatment study
© Cambridge University Press 2018. Objective To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).MethodsPatients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1-4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four conversion groups, according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.ResultsOf the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22-33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22-33 days (80.1%), and fewer were converted over 1-7 days (2.4%), 8-14 days (6.5%), or 15-21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22-33 days (44.4%) than in other conversion groups (62.5-84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.ConclusionThe majority of patients were cross-titrated to brexpiprazole over a period of 22-33 days, by investigators\u27 choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients\u27 needs
A nucleotide insertion and frameshift cause albumin KĂ©nitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges
Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-59
Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections
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Pharmacological therapies in post stroke recovery: Recommendations for future clinical trials
Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. © 2013 Springer-Verlag Berlin Heidelberg
Nova planilha de sistematização da produção (Nova PSP): ferramenta de apoio no diagnóstico e intervenção em unidades de produção familiar com atividade leiteira.
Definição do problema; Proposta de um novo instrumento de análise de sistemas de produção com atividade leiteira; MĂ©todo de construção participativa da planilha; CaracterĂsticas e funcionalidades da nova PSPbitstream/item/177970/1/DT-156-impresso.pdf; bitstream/item/223509/1/PSP-Leite-versao-7.2.xls
Multidisciplinary estimates of connectivity and population structure suggest the use of multiple units for the conservation and management of meagre, Argyrosomus regius
Information on population structure and connectivity of targeted species is key for proper implementation of spatial conservation measures. We used a combination of genomics, biophysical modelling, and biotelemetry to infer the population structure and connectivity of Atlantic meagre, an important fisheries resource throughout its distribution. Genetic samples from previously identified Atlantic spawning locations (Gironde, Tejo, Guadalquivir, Banc d’Arguin) and two additional regions (Algarve and Senegal) were analysed using genome-wide SNP-genotyping and mitochondrial DNA analyses. Biophysical models were conducted to investigate larval dispersal and connectivity from the known Atlantic spawning locations. Additionally, thirteen fish were double-tagged with biotelemetry transmitters off the Algarve (Portugal) to assess movement patterns and connectivity of adult individuals. This multidisciplinary approach provided a robust overview of meagre population structure and connectivity in the Atlantic. Nuclear SNP-genotyping showed a clear differentiation between the European and African populations, with significant isolation of the few known Atlantic spawning sites. The limited level of connectivity between these subpopulations is potentially driven by adults, capable of wide-ranging movements and connecting sites 500 km apart, as evidenced by tagging studies, whilst larval dispersal inferred by modelling is much more limited (average of 52 km; 95% of connectivity events up to 174 km). Our results show sufficient evidence of population structure, particularly between Africa and Europe but also within Europe, for the meagre to be managed as separate stocks. Additionally, considering the low degree of larvae connectivity, the implementation of marine protected areas in key spawning sites could be crucial towards species sustainability
Previsão de indicadores econômicos individuais na pecuária leiteira.
O presente trabalho objetivou a obtenção de um modelo preditivo e didático capaz de representar a influência dos indicadores de desempenho da produção leiteira nos aspectos econômicos da atividade.SBIAGRO
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