Miracle-dz/UniFAR-FTUs huggingface dataset:
Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli

Toward Microbial Taxol Taxol, a minor chemical constituent of yew tree bark, has provided a potent cancer treatment. Production methods presently rely on plant cell cultures. Ajikumar et al. (p. 70; see the Perspective by Liu and Khosla) engineered Escherichia coli cells to produce a key taxol precursor, in which the polycyclic carbon skeleton is intact. The approach relied on optimizing the relative activity of two pathways, the first of which synthesized isoprenoid building blocks that were then stitched together with the second pathway. Accumulation of indole as a by-product inhibited the isoprenoid pathway—an insight that should facilitate more efficient engineered biosynthesis of a wide range of commercially important isoprenoid derivatives. Engineered bacteria synthesize a precursor to a potent cancer drug, raising prospects for efficient production of analogs. Taxol (paclitaxel) is a potent anticancer drug first isolated from the Taxus brevifolia Pacific yew tree. Currently, cost-efficient production of Taxol and its analogs remains limited. Here, we report a multivariate-modular approach to metabolic-pathway engineering that succeeded in increasing titers of taxadiene—the first committed Taxol intermediate—approximately 1 gram per liter (~15,000-fold) in an engineered Escherichia coli strain. Our approach partitioned the taxadiene metabolic pathway into two modules: a native upstream methylerythritol-phosphate (MEP) pathway forming isopentenyl pyrophosphate and a heterologous downstream terpenoid–forming pathway. Systematic multivariate search identified conditions that optimally balance the two pathway modules so as to maximize the taxadiene production with minimal accumulation of indole, which is an inhibitory compound found here. We also engineered the next step in Taxol biosynthesis, a P450-mediated 5α-oxidation of taxadiene to taxadien-5α-ol. More broadly, the modular pathway engineering approach helped to unlock the potential of the MEP pathway for the engineered production of terpenoid natural products.
Reversibility of cardiovascular changes in extreme obesity. Effects of weight reduction through jejunoileostomy.

The effects of marked weight reduction on cardiovascular function in extreme obesity were studied before and on average 2 years after jejunoileostomy. In 17 female and 5 male patients, mean age 36 years, with obesity as the sole diagnosis, circulatory data were obtained at rest and during exercise through right heart catheterization. Blood volume and heart volume were measured and ECG was recorded at rest and during exercise. A mean weight loss of 58.1 kg reduced percentage overweight from 104 to 39%. Resting oxygen consumption and cardiac output fell in proportion to weight loss. A slightly hyperkinetic central circulation was observed during exercise. Stroke volume fell parallel to the decrease in blood volume and heart volume. Systemic arterial pressure declined, while systemic arterial resistance did not change. Left ventricular stroke work diminished. Although lower than preoperatively, the filling pressures of the right and left side of the heart were high in relation to cardiac output compared with healthy subjects. ECG at rest and during exercise remained normal. Thus, despite reductions in heart size and left ventricular stroke work, evidence of left ventricular dysfunction persisted. The observations indicate that the circulatory effects of gross obesity are largely reversible over weight loss periods of up to 3.5 years, apart from signs of a reduced myocardial wall compliance. The clinical implication seems to be that therapeutic weight-reducing intervention should be made at a younger age.
Stress and Seizures: Exploring the associations between stress and epileptic and psychogenic non-epileptic seizures

Stress is one of the most frequently self-identified seizure precipitants in patients with epilepsy, and psychogenic non-epileptic seizures (PNES) are by definition associated with psychological distress. Stress is a multifaceted phenomenon, yet few studies have systematically examined its different components in patients with seizures. The main aim of this thesis was therefore to assess the association between stress and seizures using a combination of stress measures, and to develop an intervention targeting stress in patients with seizures. The first study prospectively explored a range of psychological and physiological stress markers in patients undergoing video-telemetry. A diurnal pattern was observed in the physiological measures but, whereas some of the physiological measures were shown to be associated with each other, no close relationship was found with self-reported stress. Notably, none of the stress measures predicted occurrence of epileptic seizures or PNES; however, the occurrence of seizures was found to predict greater self-reported stress and autonomic arousal up to 12 hours after the seizures. A second part of the study assessed implicit attentional responses to stress-related stimuli and suggested patients with epilepsy show heightened vigilance towards threat (especially seizure threat), associated with increased autonomic arousal. A self-help stress-management intervention, developed as part of the second study, was evaluated in a pilot randomised controlled trial. Results from the pilot demonstrated the intervention was acceptable and provided preliminary evidence for its effectiveness in reducing self-perceived stress. Further evaluation in a larger trial may be justified, although future studies should include measures to reduce the high attrition rates observed in the pilot study. Ultimately, examination of the role of stress in seizure disorders continues to be an important area for future research. Simple interventions such as the one developed in this thesis could be a useful complementary treatment option for reducing the distress associated with seizures.
Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production

In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID50 suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication.
Measuring Life Insurance Service Quality: An Empirical Assessment of SERVQUAL Instrument

With the entry of so many players in the field and the consequent competitive activism, the entire gamut of the service sector is witnessing a multi-dimensional, purposeful, consumer-friendly approach, shedding off the lethargy that had come to be associated with the sector. One of the leading insurance companies of the service sector, Life Insurance Corporation (LIC) of India has experienced an equally profound impact of competition. One of the greatest challenges forcing the life insurance player is to differentiate its services through quality improvement. The aim of this paper is to test the reliability and to examine the dimensionality of SERVQUAL instrument in the life insurance sector. Besides, the study has identified deficiencies in the specific areas of service quality where concentrated efforts are required to be made. Data has been collected from 337 customers from three cities of Punjab to know their perceptions and expectations level at seven point Likert scale towards service quality of LIC. The findings of the study indicate that the gap scores do not merge into five dimensions of service quality; rather, the perception scores merge into three dimensions. Evidently, SERVQUAL instrument cannot be applicable to the Indian life insurance sector and further research is necessitated to comprehend the service quality within the Indian context.
Hidden star-formation in the cluster of galaxies Abell 1689

At a redshift of 0.18, Abell 1689 is so far the most distant cluster of galaxies for which substantial mid–infrared (MIR) data have been published. Its mapping with the ISOCAM camera onboard the ISO satellite allowed the detection of 30 cluster members at 6.75 ( LW 2 filter) and 16 cluster members at 15 ( LW 3 filter) within a clustercentric radius of 0.5 Mpc [CITE][ Paper I]Fadda00b. We present here the follow–up optical photometric and spectroscopic observations which were used to study the individual properties of the galaxy members of A1689. We confirm the high fraction of blue galaxies initially reported in this rich cluster by [CITE], that was challenged by some subsequent studies. We discuss the spectral and morphological properties of all cluster members in our spectroscopic sample, and of the MIR–detected galaxies in particular. Sources with a low [ 15 ] /[ 6.75 ] flux ratio typically consist of luminous passive early–type galaxies while those with a high MIR color index are mainly luminous, blue, emission–line, morphologically disturbed spirals, i.e. the star–forming galaxies usually associated with the “Butcher–Oemler” effect. On the other hand, at least 30% of the 15 sources have optical counterparts showing no evidence for current star–formation activity, while their 15 emission is most likely due to obscured star formation. We argue that the LW 3 luminosity measured in the cluster members is a reliable tracer of the total infrared luminosity which in A1689 galaxies peaks at $\mbox{$L_{\mbox{IR}}$}= 6.2 \times 10^{10}~L_{\odot}$. We derive from a star–formation rate free of dust extinction, SFR (IR), which we compare with that determined in the optical from the flux of the emission line, SFR (opt). The highest total star formation rates (11 ) and dust extinction are measured in those galaxies exhibiting in their optical spectrum a signature of a dusty starburst. In contrast, none of the galaxies with post-starburst optical spectra has been detected by ISOCAM down to a 15 flux limit corresponding to 1.4 . We find a median SFR (IR) of the LW 3–detected galaxies of 2 that is ten times higher than the median SFR (opt) of the – detected galaxies. The ratio SFR (IR)/ SFR (opt) is in fact very high, ranging between 10 and 100 for LW 3–detected galaxies with emission. We conclude that a major part, at least 90%, of the star formation activity taking place in Abell 1689 is hidden. Whether the high extinction measured in the star-forming cluster members results from the cluster environment itself or reflects a comparable extinction in the coeval field is still unclear.
Strathprints Institutional Repository Noise Expresses Exponential Growth under Regime Switching

Strathprints is designed to allow users to access the research output of the University of Strathclyde. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (http://strathprints.strath.ac.uk/) and the content of this paper for research or study, educational, or not-for-profit purposes without prior permission or charge. This is an author produced version of a paper published in Systems and Control Letters, 58 (9). pp. 691-699. ISSN 0167-6911. This version has been peer-reviewed but does not include the final publisher proof corrections, published layout or pagination. Strathprints is designed to allow users to access the research output of the University of Strathclyde. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (http://strathprints.strath.ac.uk) and the content of this paper for research or study, educational, or not-for-profit purposes without prior permission or charge. You may freely distribute the url Abstract Consider a given system under regime switching whose solution grows at most polynomially, and suppose that the system is subject to environmental noise in some regimes. Can the regime switching and the environmental noise work together to make the system change significantly? The answer is yes. In this paper, we will show that the regime switching and the environmental noise will make the original system whose solution grows at most polynomially become a new system whose solution will grow exponentially. In other words, we reveal that the regime switching and the environmental noise will exppress the exponential growth.
Fully Differentiated HIV-1 Specific CD8+ T Effector Cells Are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection

Background CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-γ+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses. Methodology/Principal Findings We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were “Controllers” (median 1140 RNA copies/ml plasma, range<50 to 2520), and 20 “progressors” of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to >750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated. Conclusions/Significance These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function.
Medically Relevant Acinetobacter Species Require a Type II Secretion System and Specific Membrane-Associated Chaperones for the Export of Multiple Substrates and Full Virulence

Acinetobacter baumannii, A. nosocomialis, and A. pittii have recently emerged as opportunistic human pathogens capable of causing severe human disease; however, the molecular mechanisms employed by Acinetobacter to cause disease remain poorly understood. Many pathogenic members of the genus Acinetobacter contain genes predicted to encode proteins required for the biogenesis of a type II secretion system (T2SS), which have been shown to mediate virulence in many Gram-negative organisms. Here we demonstrate that Acinetobacter nosocomialis strain M2 produces a functional T2SS, which is required for full virulence in both the Galleria mellonella and murine pulmonary infection models. Importantly, this is the first bona fide secretion system shown to be required for virulence in Acinetobacter. Using bioinformatics, proteomics, and mutational analyses, we show that Acinetobacter employs its T2SS to export multiple substrates, including the lipases LipA and LipH as well as the protease CpaA. Furthermore, the Acinetobacter T2SS, which is found scattered amongst five distinct loci, does not contain a dedicated pseudopilin peptidase, but instead relies on the type IV prepilin peptidase, reinforcing the common ancestry of these two systems. Lastly, two of the three secreted proteins characterized in this study require specific chaperones for secretion. These chaperones contain an N-terminal transmembrane domain, are encoded adjacently to their cognate effector, and their disruption abolishes type II secretion of their cognate effector. Bioinformatic analysis identified putative chaperones located adjacent to multiple previously known type II effectors from several Gram-negative bacteria, which suggests that T2SS chaperones constitute a separate class of membrane-associated chaperones mediating type II secretion.
Attachment and the Metabolic Syndrome in Midlife: The Role of Interview-Based Discourse Patterns

Objective Adult attachment discourse patterns and current family relationship quality were examined as correlates of health behaviors and number of metabolic syndrome (MetS) criteria met, and as mediators of the link between childhood adversity and these health outcomes. Methods A sample of 215 white/European American and black/African American adults aged 35 to 55 years were examined using a cross-sectional study design. Discourse was assessed with the Adult Attachment Interview, using coherence (a marker of attachment security), unresolved trauma/loss (a marker of disorganized cognitions related to trauma or loss), and idealization (minimizing stressful experiences and their impact) scores. Relationship quality, adverse childhood experiences, and current depressive symptoms were assessed, as were health behaviors of diet, exercise, and smoking. MetS includes obesity, elevated blood pressure, elevated fasting glucose, high triglycerides, and low high-density lipoprotein cholesterol. Results Using path analysis and including childhood adversity severity and depressive symptoms in the model, both Adult Attachment Interview coherence and unresolved trauma/loss were directly linked to the number of MetS criteria (r = 0.186 and r = 0.170, respectively). Idealization was indirectly linked to MetS through poor diet (r = 0.183). The final model explained 21% of the variance in scores for the number of MetS criteria met. Conclusions Insecure adult attachment is associated with increased risk of MetS.
Two remarks on the Shrinking Target Property

We show that a translation of vector V on the torus has the monotone shrinking target property if and only if the vector V is of constant type. Then, using reparametrizations of linear flows, we show that there exist area preserving real analytic maps of the three torus that are mixing of all orders and do not enjoy the monotone shrinking target property.
Socializing at Work: Evidence from a Field Experiment with Manufacturing Workers

Through a field experiment at a seafood-processing plant, I examine how working alongside friends affects employee productivity and how this effect is heterogeneous with respect to an employee’s personality. This paper presents two main findings. First, worker productivity declines when a friend is close enough to socialize with. Second, workers who are higher on the conscientiousness scale show smaller productivity declines when working alongside a friend. Estimates suggest that a median worker is willing to pay 4.5 percent of her wage to work next to friends. (JEL C93, J24, J28, J31, L66, O15, P23)
Preliminary report of familial clustering of EEG measures in ADHD

The purpose of the present study is to examine the familiality of electroencephalographic (EEG) measures among affected sibling pairs with Attention‐Deficit Hyperactivity Disorder (ADHD). EEG was recorded during baseline (eyes open and eyes closed) and cognitive activation conditions on a sample of 58 children with ADHD (27 multiplex families), ages 6–18. EEG power in three frequency bands: theta (4–7 Hz), alpha (8–12 Hz) and beta (12–20 Hz) was tested for sibling correlation, familial co‐segregation and association with behavioral task performance on a sustained attention task. Sibling correlation for EEG measures was moderate during baseline conditions and significantly higher for the cognitive activation condition. Familial clustering of frontal and parietal alpha power was evident, but only during the cognitive activation condition. Theta and alpha power correlated significantly with CPT response variability and omission errors, respectively. Cognitive task performance did not exhibit familial clustering in our sample. EEG measures (i.e., alpha power) recorded during cognitive activation is a strongly familial trait in ADHD and may be a putative endophenotype for ADHD. © 2007 Wiley‐Liss, Inc.
Inactivation of Escherichia coli by titanium dioxide photocatalytic oxidation

Titanium dioxide in the anatase crystalline form was used as a photocatalyst to generate hydroxyl radicals in a flowthrough water reactor. Experiments were performed on pure cultures of Escherichia coli in dechlorinated tap water and a surface water sample to evaluate the disinfection capabilities of the reactor. In water devoid of significant amounts of inorganic-radical scavengers, rapid cell death was observed with both pure cultures and members of the indigenous flora in a natural water sample.
1 VANET : Superior System for Content Distribution in Vehicular Network Applications

Vehicular connectivity can be fairly considered a future killer application, adding extra value to the car industry and operator’s services. Its main feature is to provide car safety and passenger comfort. Thus the issue of content distribution for these emerging vehicular applications needs to be handled carefully. In this paper we have done comparative study of different systems that can be used for distributing data in vehicular network applications and shown that Vehicular Ad hoc Network (VANET) is the most suitable solution for this purpose.
Signaling causal coherence relations

Signaling of relations is an open question in rhetorical structure theory (RST). Discourse markers are the unmistakable signals of a relation. However, it may be argued that all relations – and not only those involving discourse markers – are signaled in some way. Based on this assumption, this article focuses on two causal relations, ‘Cause’ and ‘Result’, working on an RST double-annotated corpus in Spanish. The main objectives are to identify different signals of Cause and Result relations and to evaluate the ambiguity resulting from those signals. Results demonstrate that a) almost all Cause and Result relations on the corpus are signaled; b) each signal obtains differentiated annotation agreements; and c) patterns of annotation disagreement are grounded in the nature of the signal and not in the relations’ semantic features.
A comparative study of several dynamic time-warping algorithms for connected-word recognition

Several different algorithms have been proposed for time registering a test pattern and a concatenated (isolated word) sequence of reference patterns for automatic connected-word recognition. These algorithms include the two-level, dynamic programming algorithm, the sampling approach and the level-building approach. In this paper, we discuss the theoretical differences and similarities among the various algorithms. An experimental comparison of these algorithms for a connected-digit recognition task is also given. The comparison shows that for typical applications, the level-building algorithm performs better than either the two-level DP matching or the sampling algorithm.