Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of Minicellulosomes on the Surface of Bacillus subtilis

ABSTRACT To cost-efficiently produce biofuels, new methods are needed to convert lignocellulosic biomass into fermentable sugars. One promising approach is to degrade biomass using cellulosomes, which are surface-displayed multicellulase-containing complexes present in cellulolytic Clostridium and Ruminococcus species. In this study we created cellulolytic strains of Bacillus subtilis that display one or more cellulase enzymes. Proteins containing the appropriate cell wall sorting signal are covalently anchored to the peptidoglycan by coexpressing them with the Bacillus anthracis sortase A (SrtA) transpeptidase. This approach was used to covalently attach the Cel8A endoglucanase from Clostridium thermocellum to the cell wall. In addition, a Cel8A-dockerin fusion protein was anchored on the surface of B. subtilis via noncovalent interactions with a cell wall-attached cohesin module. We also demonstrate that it is possible to assemble multienzyme complexes on the cell surface. A three-enzyme-containing minicellulosome was displayed on the cell surface; it consisted of a cell wall-attached scaffoldin protein noncovalently bound to three cellulase-dockerin fusion proteins that were produced in Escherichia coli. B. subtilis has a robust genetic system and is currently used in a wide range of industrial processes. Thus, grafting larger, more elaborate minicellulosomes onto the surface of B. subtilis may yield cellulolytic bacteria with increased potency that can be used to degrade biomass.
Focusing on volatility information instead of portfolio weights as an aid to investor decisions

When faced with the challenge of forming a portfolio containing a risky and a risk-free asset, investors tend to apply the same portfolio weights independently of the volatility of the risky asset. This “percentage heuristic” can lead to different levels of portfolio risk when the same investor is presented with a more or a less risky asset. Using four experiments, we show that asking investors to choose the return distribution for their portfolio while keeping the exact portfolio weights unknown leads to greater similarity in levels of portfolio volatility (across different levels of risk of the risky asset) than asking investors to choose this distribution while additionally facing the portfolio weights. Higher consistency in risk taking is obtained both between and within test subjects.
Economic Development Incentives

After establishing a way of classifying economic development incentives, this article examines four different explanations of why cities differ in their willingness to provide such incentives to encourage business growth. In order of explanatory power the explanations are citizen need, administrative capacity, fiscal stress, and the process of growth. Specific types of cities are more willing to use some incentives than others. Some underlying rules are suggested to explain why city officials make the decisions they do about economic development issues. It is the symbolic value of the actions rather than their concrete consequences that motivate much of local economic development activity.
Phylogenetic Characterization of Virulence and Resistance Phenotypes of Pseudomonas syringae

ABSTRACT Individual strains of the plant pathogenic bacterium Pseudomonas syringae vary in their ability to produce toxins, nucleate ice, and resist antimicrobial compounds. These phenotypes enhance virulence, but it is not clear whether they play a dominant role in specific pathogen-host interactions. To investigate the evolution of these virulence-associated phenotypes, we used functional assays to survey for the distribution of these phenotypes among a collection of 95 P. syringae strains. All of these strains were phylogenetically characterized via multilocus sequence typing (MLST). We surveyed for the production of coronatine, phaseolotoxin, syringomycin, and tabtoxin; for resistance to ampicillin, chloramphenicol, rifampin, streptomycin, tetracycline, kanamycin, and copper; and for the ability to nucleate ice at high temperatures via the ice-nucleating protein INA. We found that fewer than 50% of the strains produced toxins and significantly fewer strains than expected produced multiple toxins, leading to the speculation that there is a cost associated with the production of multiple toxins. None of these toxins was associated with host of isolation, and their distribution, relative to core genome phylogeny, indicated extensive horizontal genetic exchange. Most strains were resistant to ampicillin and copper and had the ability to nucleate ice, and yet very few strains were resistant to the other antibiotics. The distribution of the rare resistance phenotypes was also inconsistent with the clonal history of the species and did not associate with host of isolation. The present study provides a robust phylogenetic foundation for the study of these important virulence-associated phenotypes in P. syringae host colonization and pathogenesis.
Galectin-2 at the enterocyte brush border of the small intestine

The brush border of pig small intestine is a local hotspot for β-galactoside-recognizing lectins, as evidenced by its prominent labeling with fluorescent lectin PNA. Previously, galectins 3-4, intelectin, and lectin-like anti-glycosyl antibodies have been localized to this important body boundary. Together with the membrane glycolipids these lectins form stable lipid raft microdomains that also harbour several of the major digestive microvillar enzymes. In the present work, we identified a lactose-sensitive 14-kDa protein enriched in a microvillar detergent resistant fraction as galectin-2. Its release from closed, right-side-out microvillar membrane vesicles shows that at least some of the galectin-2 resides at the lumenal surface of the brush border, indicating that it plays a role in the organization/stabilization of the lipid raft domains. Galectin-2 was released more effectively from the membrane by lactose than was galectin-4, and surprisingly, it was also released by the noncanonical disaccharides sucrose and maltose. Furthermore, unlike galectin-4, galectin-2 was preferentially coimmunoisolated with sucrase-isomaltase rather than with aminopeptidase N. Together, these results show that the galectins are not simply redundant proteins competing for the same ligands but rather act in concert to ensure an optimal cross-linking of membrane glycolipids and glycoproteins. In this way, they offer a maximal protection of the brush border against exposure to bile, pancreatic enzymes and pathogens.
An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer.

BACKGROUND High-level expression of epithelial cell adhesion molecule (EpCAM) is associated with unfavorable prognosis in breast cancer. This study was designed to investigate two doses of the fully human IgG1 anti-EpCAM antibody adecatumumab (MT201) in patients with metastatic breast cancer (MBC). METHODS A total of 109 patients were stratified into high- and low-level EpCAM expression by immunohistochemical staining of primary tumors and subsequently randomly assigned to receive monotherapy with either high- (6 mg/kg every two weeks (q2w)) or low-dose adecatumumab (2 mg/kg/ q2w) until disease progression. RESULTS No complete or partial tumor responses could be confirmed by central RECIST assessment. The probability for tumor progression was significantly lower in patients receiving high-dose adecatumumab and expressing high levels of EpCAM (hazard ratio 0.43; P = 0.0057 versus low dose and low EpCAM). Three of 18 patients with highest EpCAM expression treated with adecatumumab developed new metastases up to week 6, compared with 14 of 29 patients with low EpCAM. Most frequent treatment-related adverse events (high dose/low dose) were chills (59%/20%), nausea (55%/18%), fatigue (39%/23%) and diarrhea (43%/7%). CONCLUSIONS Single-agent adecatumumab shows dose- and target-dependent clinical activity in EpCAM-positive MBC, albeit no objective tumor regression. Further investigation of adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden is warranted.
The Reaction of Stock-Bond Correlations to Risk Aversion and Real Time Macroeconomic Announcements

Using a high-frequency dataset, we analyze the effects of risk-aversion and real-time macroeconomic variables on both conditional variances and stock-bond correlations in the Eurozone. We use a generalized DCCX model for correlations and a GARCHX model for variances in order to separate the effects on the dependence structure from those on the volatility. We find that correlations fall as risk aversion rises even when controlling for macroeconomic announcements. Interestingly, the additional effects of the financial crisis are only small. While most macroeconomic news result in falling conditional correlations, the publication of news concerning future interest rates or inflation figures moves bond and stock prices in the same direction.
Trichloroethylene oxidation by purified toluene 2-monooxygenase: products, kinetics, and turnover-dependent inactivation

Trichloroethylene is oxidized by several types of nonspecific bacterial oxygenases. Toluene 2-monooxygenase from Burkholderia cepacia G4 is implicated in trichloroethylene oxidation and is uniquely suggested to be resistant to turnover-dependent inactivation in vivo. In this work, the oxidation of trichloroethylene was studied with purified toluene 2-monooxygenase. All three purified toluene 2-monooxygenase protein components and NADH were required to reconstitute full trichloroethylene oxidation activity in vitro. The apparent Km and Vmax were 12 microM and 37 nmol per min per mg of hydroxylase component, respectively. Ten percent of the full activity was obtained when the small-molecular-weight enzyme component was omitted. The stable oxidation products, accounting for 84% of the trichloroethylene oxidized, were carbon monoxide, formic acid, glyoxylic acid, and covalently modified oxygenase proteins that constituted 12% of the reacted [14C]trichloroethylene. The stable oxidation products may all derive from the unstable intermediate trichloroethylene epoxide that was trapped by reaction with 4-(p-nitrobenzyl)pyridine. Chloral hydrate and dichloroacetic acid were not detected. This finding differs from that with soluble methane monooxygenase and cytochrome P-450 monooxygenase, which produce chloral hydrate. Trichloroethylene-dependent inactivation of toluene 2-monooxygenase activity was observed. All of the protein components were covalently modified during the oxidation of trichloroethylene. The addition of cysteine to reaction mixtures partially protected the enzyme system against inactivation, most notably protecting the NADH-oxidoreductase component. This suggested the participation of diffusible intermediates in the inactivation of the oxidoreductase.
Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease.

BACKGROUND Meningococcal disease occurs after colonization of the nasopharynx with Neisseria meningitidis. Surfactant protein (SP)-A and SP-D are pattern-recognition molecules of the respiratory tract that activate inflammatory and phagocytic defences after binding to microbial sugars. Variation in the genes of the surfactant proteins affects the expression and function of these molecules. METHODS Allele frequencies of SP-A1, SP-A2, and SP-D were determined by polymerase chain reaction in 303 patients with microbiologically proven meningococcal disease, including 18 patients who died, and 222 healthy control subjects. RESULTS Homozygosity of allele 1A1 of SP-A2 increased the risk of meningococcal disease (odds ratio [OR], 7.4; 95% confidence interval [CI], 1.3-42.4); carriage of 1A5 reduced the risk (OR, 0.3; 95% CI, 0.1-0.97). An analysis of the multiple single-nucleotide polymorphisms in SP-A demonstrated that homozygosity for alleles encoding lysine (in 1A1) rather than glutamine (in 1A5) at amino acid 223 in the carbohydrate recognition domain was associated with an increased risk of meningococcal disease (OR, 6.7; 95% CI, 1.4-31.5). Carriage of alleles encoding lysine at residue 223 was found in 61% of patients who died, compared with 35% of those who survived (OR adjusted for age, 2.9; 95% CI, 1.1-7.7). Genetic variation of SP-A1 and SP-D was not associated with meningococcal disease. CONCLUSIONS Gene polymorphism resulting in the substitution of glutamine with lysine at residue 223 in the carbohydrate recognition domain of SP-A2 increases susceptibility to meningococcal disease, as well as the risk of death.
Is the Economic Crisis Impairing Convergence in Innovation Performance Across Europe?

Are EU Member States converging in terms of their innovative effort? To what extent is the current economic downturn impairing the convergence across the European Union countries in innovation performance? Using macro and micro data, this article shows that the EU Member States have converged in their innovative potential over the 2004–08 period. The economic crisis of Autumn 2008 has an impact on innovative investment in almost all EU countries, but the catch-up countries are the most affected, leading to increasing divergence. The danger of growing disparities in innovative capabilities may lead to divergence also in income and well-being. The article discusses some of the innovation policies that can be carried out at the EU level to facilitate cohesion.
Perceptions of cultural competency of undergraduate nursing students

Purpose: The purpose of this study was to examine the level of cultural competence of undergraduate nursing students at a large Midwestern University. Background: Developing cultural competence of nurses is critical to meet the needs of our growing diverse society. Methods: A convenience sample of 150 undergraduate nursing students completed a one-time questionnaire assessing students’ cultural competence. Results: Nursing students’ rated their overall knowledge and comfort moderate to poor with only 28% rated themselves as very comfortable and 15% as very skillful in providing culturally competent care. Students rated their knowledge and comfort highest in taking a family history, whereas, the lowest scores were related to pregnancy and childbirth, death and dying, and organ donation in other cultures. Conclusions: Findings suggest that nursing students feel inadequately prepared to provide culturally competent care.
Evaluating Muscle Mass in Survivors of Acute Respiratory Distress Syndrome: A 1-Year Multicenter Longitudinal Study*

Objectives: Rapid muscle wasting occurs during acute respiratory failure, resulting in muscle weakness and functional impairments. This study examines survivors’ body composition in the year after acute respiratory distress syndrome and tests associations of patient characteristics, hospital exposures, and survivors’ strength and physical functioning with whole body percent lean mass. Design: Prospective cohort study with 6- and 12-month follow-up. Setting: National study enrolling patients from five study centers. Patients: Acute respiratory distress syndrome survivors (n = 120). Interventions: None. Measurements and Main Results: Lean and fat mass from dual energy x-ray absorptiometry. On average, survivors gained whole body total mass (+1.4 kg; 0.1–2.7) and fat mass (+1.2 kg; 0.2–2.2) and maintained lean mass (+0.2 kg; –0.4 to 0.8) between 6 and 12 months. Proportionally, percent fat mass increased and percent lean mass decreased for the whole body, trunk, and legs (p < 0.05). Greater whole body percent lean mass was associated with younger age, male sex, and lower baseline body mass index, but not other patient characteristics or ICU/hospital exposures. Greater percent lean mass was also significantly associated with gait speed and 6-minute walk distance, but not volitional strength or self-reported functional status. Conclusions: In the first year after acute respiratory distress syndrome, patients gained fat mass and maintained lean mass. We found no association of whole body percent lean mass with commonly hypothesized hospital risk factors. Direct measurement of body composition and performance-based functional measures may be helpful for understanding functional recovery in ICU survivors.
Route Decision Behaviour in a Commuting Scenario: Simple Heuristics Adaptation and Effect of Traffic Forecast

One challenge to researchers dealing with traffic management is to find efficient ways to model and predict traffic flow. Due to the social nature of traffic, most of the decisions are not independent. Thus, in traffic systems the inter-dependence of actions leads to a high frequency of implicit co-ordination decisions. Although there are already systems designed to assist drivers in these tasks (broadcast, Internet, etc.), such systems do not consider or even have a model of the way drivers decide. Our research goal is the study of commuting scenarios, drivers' decision-making, its influence on the system as a whole, and how simulation can be used to understand complex traffic systems. The present paper addresses two key issues: simulation of driver decision-making, and the role of a traffic forecast component. The former is realised by a naive model for the route choice adaptation, where commuters behaviour is based on heuristics they evolve. The second issue is realised via a traffic control system which perceives drivers' decisions and returns a forecast, thus allowing drivers to decide the actual route selection. For validation, we use empirical data from real experiments and show that the heuristics drivers evolve lead to a situation similar to that obtained in the real experiments. As for the forecast scenario, our results confirm that a traffic system in which a large share of drivers reacts to the forecast will not develop into equilibrium. However, a more stable situation arises by introducing some individual tolerance to sub-optimal forecasts.
Islamic tourism and managing tourism development in Islamic societies: the cases of Iran and Saudi Arabia

This paper is concerned with the effects of state religion on tourism development in Muslim countries with particular reference to Iran and Saudi Arabia. Aspects of the relationship between Islam and tourism are investigated overall and issues of tourism policies, management and marketing and community involvement within the context of the two cases are discussed. The distinctive circumstances prevailing in Iran and Saudi Arabia are suggested, but more general insights are also presented into the interactions between and management of tourism and Islam. Copyright © 2009 John Wiley & Sons, Ltd.
The limits to the growth of multinational firms in a foreign market

Theories of growth for firms have suggested that slow managerial growth is a major constraint why firms cannot grow faster. This paper is built on such a view and explores the factors that may influence the growth rate of Japanese firms in a given US industry. It is found that Japanese firms that allocated more internal and international managerial resources (proxied by expatriates) to their US operations tended to achieve higher growth rates. Japanese firms that were geographically diversified and those that spread their international investment projects evenly over time also achieved higher growth rates. Copyright © 2003 John Wiley & Sons, Ltd.
Policy Analysis and Forecasting in the World Economy: A Panel Unobserved Components Approach

This paper develops a panel unobserved components model of the monetary transmission mechanism in the world economy, disaggregated into its fifteen largest national economies. This structural macroeconometric model features extensive linkages between the real and financial sectors, both within and across economies. A variety of monetary policy analysis and forecasting applications of the estimated model are demonstrated, based on a novel Bayesian framework for conditioning on judgment.
Modeling Nonignorable Nonresponse in Categorical Panel Data with an Example in Estimating Gross Labor-Force Flows

Many large-scale sample surveys use panel designs under which sampled individuals are interviewed several times before being dropped from the sample. The longitudinal data bases available from such surveys could be used to provide estimates of gross change over time. One problem in using these data to estimate gross change is how to handle the period-to-period nonresponse. This nonresponse is typically nonrandom and, furthermore, may be nonignorable in that it cannot be accounted for by other observed quantities in the data. Under the models proposed in this article, which are appropriate for the analysis of categorical data, the probability of nonresponse may be taken to be a function of the missing variable of interest. The proposed models are fit using maximum likelihood estimation. As an example, the method is applied to the problem of estimating gross flows in labor-force participation using data from the Current Population Survey and the Canadian Labour Force Survey.
The prognostic significance of beta(2)-microglobulin in patients with Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES Serum beta(2)-microglobulin (s beta(2)m) is an established prognostic factor for multiple myeloma and non-Hodgkin's lymphoma, but only limited data suggest an adverse prognostic significance for Hodgkin's lymphoma (HL). This study was undertaken to examine the impact of s beta(2)m on the prognosis of patients with HL. DESIGN AND METHODS s beta(2)m was measured by a radioimmunoassay (upper normal limit 2.4 mg/L), in pretreatment serum samples of 232 patients with HL, who were then treated with ABVD or equivalent regimens with or without radiotherapy. Multivariate survival analysis was based on Cox's proportional hazards model. RESULTS Main patients' characteristics: median age 30.5 years (14-78); 58% males; 68% nodular sclerosis, 20% mixed cellularity and 12% lymphocyte predominance; 34% B-symptoms; 24% Ann Arbor stage I, 49% II, 18% III and 9% IV. Elevated s beta(2)m levels were detected in 65/232 patients (28%) and correlated with older age (p<0.001), mixed cellularity (p=0.03), B-symptoms (p=0.002), advanced stage (p=0.02), > or = 5 involved sites (p=0.02), inguinal/iliac involvement (p=0.009), lymphocytopenia (p=0.002) and elevated lactate dehydrogenase (p=0.01). The 7-year failure free survival (FFS) was 75% vs. 72% for patients with normal vs. elevated s beta(2)m (p=0.15). The corresponding 7-year overall survival (OS) rates were 86% vs. 52% (p=0.003). In multivariate analysis, elevated s beta(2)m was not predictive of FFS, but was independently associated with inferior OS (p=0.01), along with the number of involved sites (p<0.001). INTERPRETATION AND CONCLUSIONS s beta(2)m is not a potent prognostic factor for FFS in optimally treated patients with HL. However s beta(2)m may be predictive of OS, probably due to its effect on the timing of treatment failure.