184 research outputs found
Shock Position Control for Mode Transition in a Turbine Based Combined Cycle Engine Inlet Model
A dual flow-path inlet for a turbine based combined cycle (TBCC) propulsion system is to be tested in order to evaluate methodologies for performing a controlled inlet mode transition. Prior to experimental testing, simulation models are used to test, debug, and validate potential control algorithms which are designed to maintain shock position during inlet disturbances. One simulation package being used for testing is the High Mach Transient Engine Cycle Code simulation, known as HiTECC. This paper discusses the development of a mode transition schedule for the HiTECC simulation that is analogous to the development of inlet performance maps. Inlet performance maps, derived through experimental means, describe the performance and operability of the inlet as the splitter closes, switching power production from the turbine engine to the Dual Mode Scram Jet. With knowledge of the operability and performance tradeoffs, a closed loop system can be designed to optimize the performance of the inlet. This paper demonstrates the design of the closed loop control system and benefit with the implementation of a Proportional-Integral controller, an H-Infinity based controller, and a disturbance observer based controller; all of which avoid inlet unstart during a mode transition with a simulated disturbance that would lead to inlet unstart without closed loop control
Mitochondrial precursor proteins are imported through a hydrophilic membrane environment
We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites
An efficient system for the generation of marked genetic mutants in members of the genus Burkholderia
To elucidate the function of a gene in bacteria it is vital that targeted gene inactivation (allelic replacement) can be achieved. Allelic replacement is often carried out by disruption of the gene of interest by insertion of an antibiotic-resistance marker followed by subsequent transfer of the mutant allele to the genome of the host organism in place of the wild-type gene. However, due to their intrinsic resistance to many antibiotics only selected antibiotic-resistance markers can be used in members of the genus Burkholderia, including the Burkholderia cepacia complex (Bcc). Here we describe the construction of improved antibiotic-resistance cassettes that specify resistance to kanamycin, chloramphenicol or trimethoprim effectively in the Bcc and related species. These were then used in combination with and/or to construct a series enhanced suicide vectors, pSHAFT2, pSHAFT3 and pSHAFT-GFP to facilitate effective allelic replacement in the Bcc. Validation of these improved suicide vectors was demonstrated by the genetic inactivation of selected genes in the Bcc species Burkholderia cenocepacia and B. lata, and in the non-Bcc species, B. thailandensis
Effect of the 3′-Terminal Truncation of the Human interferon-Gamma Gene on Plasmid Segregation in Escherichia Coli
Effects of a recombinant gene expression on ColE1-like plasmid segregation in Escherichia coli
<p>Abstract</p> <p>Background</p> <p>Segregation of expression plasmids leads to loss of recombinant DNA from transformed bacterial cells due to the irregular distribution of plasmids between the daughter cells during cell division. Under non-selective conditions this segregational instability results in a heterogeneous population of cells, where the non-productive plasmid-free cells overgrow the plasmid-bearing cells thus decreasing the yield of recombinant protein. Amongst the factors affecting segregational plasmid instability are: the plasmid design, plasmid copy-number, host cell genotype, fermentation conditions etc. This study aims to investigate the influence of transcription and translation on the segregation of recombinant plasmids designed for constitutive gene expression in <it>Escherichia coli </it>LE392 at glucose-limited continuous cultivation. To this end a series of pBR322-based plasmids carrying a synthetic human interferon-gamma (hIFNγ) gene placed under the control of different regulatory elements (promoter and ribosome-binding sites) were used as a model.</p> <p>Results</p> <p>Bacterial growth and product formation kinetics of transformed <it>E. coli </it>LE392 cells cultivated continuously were described by a structured kinetic model proposed by Lee et al. (1985). The obtained results demonstrated that both transcription and translation efficiency strongly affected plasmid segregation. The segregation of plasmid having a deleted promoter did not exceed 5% after 190 h of cultivation. The observed high plasmid stability was not related with an increase in the plasmid copy-number. A reverse correlation between the yield of recombinant protein (as modulated by using different ribosome binding sites) and segregational plasmid stability (determined by the above model) was also observed.</p> <p>Conclusions</p> <p>Switching-off transcription of the hIFNγ gene has a stabilising effect on ColE1-like plasmids against segregation, which is not associated with an increase in the plasmid copy-number. The increased constitutive gene expression has a negative effect on segregational plasmid stability. A kinetic model proposed by Lee et al. (1985) was appropriate for description of <it>E. coli </it>cell growth and recombinant product formation in chemostat cultivations.</p
Grey-matter abnormalities in clinical high-risk participants for psychosis
The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies
Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) – novel predictors for response and survival in gastric cancer patients
To evaluate the predictive value of a panel of gene polymorphisms involved in metabolism of 5-FU and cisplatin on clinical outcome in advanced gastric cancer patients. A total of 52 patients were enrolled in this study. DNA was extracted from paraffin-embedded tumour specimen. Genotypes were determined using PCR-RFLP. Median survival time was 6.0 months (95% CI 3.9;8.1). Overall response rate was 26%. Patients possessing the glutathione S-transferase P1-105 Valine/Valine (GSTP1-105VV) genotype showed a response rate of 67% compared to 21% in patients harbouring at least one GSTP1-105 Isoleucine (GSTP1-105I) allele (P=0.038). GSTP1-105VV patients demonstrated a significant superior median survival time of 15.0 months (95% CI 7.8;22.0) compared to 6.0 months (95% CI 5.1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15.3) compared to 6.0 months (95% CI 5.0;7.0) in patients with unfavourable TS genotypes (P=0.099). Patients harbouring the GSTP1-105II genotype and one of the unfavourable TS genotypes showed an inferior median survival time of 6.0 months (95% CI 3.9;8.1) compared to 11 months (95% CI 6,23;15,77) in patients with either GSTP1-105VV or a favourable TS genotype (P=0.044). Testing for TS and GSTP1 polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy
Uncertainty and Narratives of the Future. A Theoretical Framework for Contemporary Fertility
Explanations for fertility decisions based on structural constraints—such as labor, housing condition, or income—do not account for the contemporary fertility downturn faced by many countries in Europe. In this paper, we posit that the rise of uncertainty is central for understanding contemporary fertility dynamics. We propose a theoretical framework (the Narrative Framework) for the study of fertility decisions under uncertain conditions based on expectations, imaginaries and narratives. Relying on the idea of future–oriented action, we argue that uncertainty needs to be conceptualized and operationalized taking into account that people use works of imagination, producing their own narrative of the future. Narratives of the future are potent driving forces helping people to act according to or despite uncertainty. We present the different elements of the Narrative Framework and address its causal validity. We conclude by highlighting the advantages of taking into account the narratives of the future in fertility research
Empathetic Understanding and Deliberative Democracy
Epistemic democracy is standardly characterized in terms of “aiming at truth”. This presupposes a veritistic conception of epistemic value, according to which truth is the fundamental epistemic goal. I will raise an objection to the standard (veritistic) account of epistemic democracy, focusing specifically on deliberative democracy. I then propose a version of deliberative democracy that is grounded in non‐veritistic epistemic goals. In particular, I argue that deliberation is valuable because it facilitates empathetic understanding. I claim that empathetic understanding is an epistemic good that doesn't have truth as its primary goal
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