Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of mutations in the MHC class I peptide binding groove on the cytotoxic T lymphocyte recognition of the Kb‐restricted ovalbumin determinant

The H‐2Kb‐restricted cytotoxic T lymphocyte (CTL) response directed against ovalbumin (OVA) is specific for a region contained within the sequence OVA253‐276. In this study we have characterized this response by examining the class I‐restricted presentation of OVA peptides by the naturally occurring Kb mutant (Kbm) glycoproteins Kbm1, Kbm3, Kbm5, Kbm8, Kbm10, Kbm11 and Kbm23. To facilitate this study we derived a series of somatic cell hybrid targets expressing the various Kbm class I molecules. Experiments using bulk OVA‐specific CTL from C57BL/6 mice demonstrated that all the Kbm molecules except for Kbm1 and Kbm8 could present OVA peptides for effective T cell recognition. Clonal analysis revealed a more complex and relatively diverse pattern of CTL recognition of the Kbm/peptide combinations. This diversity is unlikely to result from the existence of multiple, independent Kb‐restricted T cell determinants within OVA, since all CTL tested were specific for a single region between residues 259 and 273. Examination of the fine specificity of Kbm presentation identified individual changes at residues 77, 80 and 116 which affected T cell recognition. The results imply that these changes do not inhibit peptide binding since some clones could recognize peptide presented by a particular Kbm molecule, while other clones could not. All three residues reside within the peptide‐binding cleft of the class I protein and are not expected to directly contact the T cell receptor. Although we did not formally demonstrate that OVA binding by Kbm vs. Kb is quantitatively identical, our results are best explained by postulating that the changes at residues 77, 80 and 116 indirectly affect T cell recognition by altering peptide conformation. Taken together our results suggest that changes within the class I binding site can profoundly modify peptide presentation without significantly inhibiting peptide‐class I association.
Safety of tacrolimus, an immunosuppressive agent, in the treatment of rheumatoid arthritis in elderly patients.

OBJECTIVE To prospectively evaluate the safety of tacrolimus in active rheumatoid arthritis (RA) in elderly patients with insufficient response to disease-modifying antirheumatic drugs (DMARDs). METHODS Fifty-seven patients aged > or =65 yr with RA for > or =6 months were enrolled in an open-label, non-controlled study. All DMARDs were discontinued and tacrolimus was administered orally once daily after the evening meal for 28 weeks. Tacrolimus, initiated at 1.5 mg/day, was increased to 3 mg/day after 6 weeks if no abnormal changes developed. Existing NSAID and oral corticosteroid (< or =7.5 mg/day prednisolone equivalent) therapy could be continued during the study. Safety was evaluated as clinical symptoms, abnormal changes in laboratory values and the development of infection. Treatment response was determined using the American College of Rheumatology (ACR) criteria for improvement. Whole blood concentrations of tacrolimus 12 h after administration were measured by high-performance liquid chromatography and tandem mass spectrometry. RESULTS Clinical adverse events developed in 25 patients (46.3%). Abnormal changes in laboratory values occurred in 25 patients (46.3%). Ten patients (18.5%) developed infection. An ACR20 response was achieved by 50.0% of efficacy-evaluable patients and ACR20 success rates (the proportion of patients achieving ACR20 response and completing the study) was 46.3%. The ACR50 response rate was 18.5% of evaluable patients. Mean blood concentration of tacrolimus was 3.3 and 5.3 ng/ml in patients receiving 1.5 and 3.0 mg daily, respectively. No relationship between its concentration and adverse reactions was observed. CONCLUSION In elderly patients with insufficient response to DMARD therapy, tacrolimus at 1.5-3.0 mg/day is safe and well-tolerated and provides clinical benefit.
The integrated watershed management planning experience in Manitoba: the local conservation district perspective

Abstract Manitoba has abundant freshwater resources, and developing and implementing integrated watershed management plans is essential to ensure a healthy future. This article provides an assessment of progress in Manitoba since the early 1990s (Mitchell and Shrubsole, 1994) regarding integrated watershed management plans. It explains current conditions, including the structural framework, governance, public consultations and First Nations participation, along with examples of experiences, successes, failures, and lessons learnt. The Water Protection Act, proclaimed in 2006, empowered conservation districts to develop and implement integrated watershed management plans as the water planning authority, and represents the most significant change.
U.S. State Minimum Wage Policies and Employment Performance Improvement

Federal, state and local departments of labor are managing the minimum wage levels. U.S. state minimum wage increases are positively associated with GRDP growth rates and education expenditure rates. Minimum wage increases are positively associated with economic capacities and human capital improvements. And U.S. state minimum wage increases are negatively associated with state citizen ideology scores. Thus, relatively conservative citizens are supporting the minimum wage increase and U.S. state governments/governors are reflecting these conser- vative citizen ideologies regardless of state governments' and state governors' ideologies. These are the strong evidences of state policy congruence in case of minimum wage policy. And politicians and public administrators should respect the evidence-based policy approaches. Specialist opinions, evaluation reports and experiences are excellent sources of evidence-based policy. Public policy decisions should be based on these evidence-based policy approaches. Especially, politicians and public administrators should manage the relationships between minimum wage policy and employment performances cautiously by using public performance measures and statistical research methods. And minimum wage policy should be harmonized with labor productivity improvement.
Renin-angiotensin system as a potential target for new therapeutic approaches in Parkinson’s disease

ABSTRACT Introduction: Currently, available therapies for Parkinson’s disease (PD) are symptomatic. Therefore, the search for neuroprotective drugs remains a top priority. Areas covered: In this review, the potential symptomatic or disease-modifying effect of drugs targeting the Renin-Angiotensin System (RAS) in PD will be explored. Expert opinion: The importance of nigrostriatal local RAS has only begun to be unraveled in the last decades. On one hand, there is a complex feedback cycle between RAS and dopamine (DA). On the other hand, RAS affects dopaminergic neurons vulnerability. Neuroprotective effects in animal PD models have been shown for the angiotensin-converting enzyme (ACE) inhibitors captopril and perindopril, and the AT1 receptor antagonists losartan, candesartan and telmisartan. These effects appear to be mediated by a reduction in the overproduction of reactive oxygen species. In a proof-of-concept, randomized, double-blind, crossover study in PD patients, perindopril enhanced the effect of levodopa without inducing dyskinesias. There has not been any clinical trial exploring the neuroprotective effect of RAS drugs, but one cohort study in hypertensive patients suggested a protective effect of ACE inhibitors on PD risk. RAS is a promising target for symptomatic and neuroprotective therapies in PD. Further studies in PD animal models and patients are warranted.
An Acute Bronchodilator Test with Tiotropium or Salmeterol Does Not Allow a Subdivision of Patients according to Responses

Background: The possibility that individual chronic obstructive pulmonary disease (COPD) patients respond better to either tiotropium or salmeterol has been suggested and an acute bronchodilator test might help to guide the choice of therapy. Objectives: We explored the responses to tiotropium and salmeterol within the first 3 h using the recommended dosages (18 µg for tiotropium and 50 µg for salmeterol) in order to verify whether there are differences in the short-term bronchodilator effects between these two long-acting bronchodilators in patients with stable COPD. Moreover, we investigated whether these differences could discriminate between the two agents. Methods: Forty consecutive patients with COPD, but in a stable phase of the disease, participated in this double-blind, double-dummy, randomized crossover study. The study involved a screening visit and 2 study days separated by at least 1 week. For determination of the onset of action, we measured FEV1 at 10, 20, 30, 60 and 90 min, and again 2 and 3 h after inhalation of single study drug. Results: At all time points, both tiotropium and salmeterol caused significant (p< 0.001) changes from baseline. A mean increase of 12% above baseline was reached 66 min (95% CI: 45–87) after tiotropium and 59 min (95% CI: 41–77) after salmeterol. Nine patients after tiotropium and 5 patients after salmeterol did not have this type of improvement. A mean increase of 200 ml above baseline was reached 76 min (95% CI: 52–101) after tiotropium and 76 min (95% CI: 52–100) after salmeterol. Eighteen patients after tiotropium and 15 patients after salmeterol did not have this improvement. Twenty-one patients after tiotropium and 24 patients after salmeterol reached an improvement that was at the same time 12% and 200 ml greater than baseline. Conclusions: These data clearly show that the bronchodilator effects of tiotropium and salmeterol within the first hours after their acute administration are similar in patients with stable COPD when they are evaluated as mean changes from baseline in FEV1. Therefore, they question the direct therapeutic relevance of a subdivision of patients according to bronchodilator responses to tiotropium or salmeterol.
Exercise Associated Genes in Rat Colon Mucosa: Upregulation of Ornithin Decarboxylase-1

Epidemiology has revealed that physical activity is an important lifestyle factor that reduces the risk of colon cancer. However, the underlying mechanisms of this protective effect have so far not been defined. The aim of this study was to identify molecular targets of physical activity in rat colon mucosa by employing our voluntary exercise model. Twenty male rats underwent a 12-week exercise program, with 9 additional rats serving as a control group. Running distances, body weights and heart weights as measures of physical adaptations were recorded, and changes in mRNA steady-state levels of marker genes involved in vascularization (VEGF, HIF-1 alpha, ODC-1), apoptosis (Bcl-2, PPAR gamma) and prostaglandin synthesis (COX-2) were determined by qRT-PCR. The four housekeeping genes GAPDH, beta-actin, 18S and ALDA served as reference genes. Recorded running distances showed great inter-individual differences resulting in three different groups of low (L-EX, < 2629 m/night; n=5), moderate (M-EX, 3003 - 7458 m/night; n=10) and high (H-EX, > 8314 m/night; n=5) physical activity. The M-EX and H-EX group revealed significant (p<0.05) adaptive changes with an increase in heart mass per kg body weight and a decrease in mean body weight. Amongst the marker genes studied by mRNA expression analysis only ODC-1 appears to be differentially expressed. Its 1.8-fold increased steady-state mRNA level in the H-EX group suggests that synthesis of polyamines may be increased by physical activity. This new finding could provide a link between extensive physical activity and its protective effects on colon cancer development.
A system biology study of BALF from patients affected by idiopathic pulmonary fibrosis (IPF) and healthy controls

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by progressive loss of the alveolar integrity, recruitment, and activation of myofibroblast, and excessive collagen deposition that resulted in loss of parenchymal architecture and lung function. Although etiology is unknown, major risk factor of disease development is represented by cigarette smoke or exposure to dust.
INDUCTIVE REASONING IN MARKETING RESEARCH TO RESPOND THE FUTURE MARKET CHALLENGES

This paper aims to provide the definition of inductive reasoning and explain its importance in the field of business and management research to respond to the future market challenges. On this paper, we will first describe the basic understandings of two types of scientific reasoning concepts which are deductive and inductive, including the idea of positivism and interpretivism, as well as its relevance to natural and social sciences studies. Then, we will continue to explain that inductive reasoning, however, is rarely used in business and management research particularly in some of Indonesia’s top higher education institutions. Furthermore, in order to show the importance of inductive reasoning, a case study of Starbucks and 7-Eleven in Indonesia will be presented with reflection to argument by Handy (1993). This paper will finally conclude by emphasizing the importance of inductive reasoning in business and management research and suggest future recommendations towards business and management research in Indonesia particularly on the higher education institutions. Keywords: inductive reasoning, future market challenges
Characterization of the Avian PathogenicEscherichia coli Hemagglutinin Tsh, a Member of the Immunoglobulin A Protease-Type Family of Autotransporters

ABSTRACT We reported earlier that a single gene, tsh, isolated from a strain of avian pathogenic Escherichia coli (APEC) was sufficient to confer on E. coli K-12 a hemagglutinin-positive phenotype and that the deduced sequence of the Tsh protein shared homology to the serine-type immunoglobulin A (IgA) proteases of Neisseria gonorrhoeae and Haemophilus influenzae. In this report we show that E. coli K-12 containing the recombinant tsh gene produced two proteins, a 106-kDa extracellular protein and a 33-kDa outer membrane protein, and was also able to agglutinate chicken erythrocytes. N-terminal sequence data indicated that the 106-kDa protein, designated Tshs, was derived from the N-terminal end of Tsh after the removal of a 52-amino-acid N-terminal signal peptide, while the 33-kDa protein, designated Tshβ, was derived from the C-terminal end of Tsh starting at residue N1101. The Tshsdomain contains the 7-amino-acid serine protease motif that includes the active-site serine (S259), found also in the secreted domains of the IgA proteases. However, site-directed mutagenesis of S259 did not abolish the hemagglutinin activity or the extracellular secretion of Tshs indicating that host-directed proteolysis was mediating the release of Tshs. Studies with an E. coli K-12ompT mutant strain showed that the surface protease OmpT was not needed for the secretion of Tshs. Tsh belongs to a subclass of the IgA protease family, which also includes EspC of enteropathogenic E. coli, EspP of enterohemorragic E. coli, and SepA and VirG of Shigella flexneri, which seem to involve a host endopeptidase to achieve extracellular release of their N-terminal domains. In proteolytic studies conducted in vitro, Tshs did not cleave the substrate of the IgA proteases, human IgA1 or chicken IgA, and did not show proteolytic activity in a casein-based assay. Correlation of Tsh expression and hemagglutination activity appears to be a very complex phenomenon, influenced by strain and environmental conditions. Nevertheless, for both APEC and recombinant E. coli K-12 strains containing thetsh gene, it was only the whole bacterial cells and not the cell-free supernatants that could confer hemagglutinin activity. Our results provide insights into the expression, secretion, and proteolytic features of the Tsh protein, which belongs to the growing family of gram-negative bacterial extracellular virulence factors, named autotransporters, which utilize a self-mediated mechanism to achieve export across the bacterial cell envelope.
Aortic annulus diameter measurement: what is the best modality?

PURPOSE The purpose of this study was to clarify the most suitable method to measure the aortic annulus diameter. PATIENTS AND METHODS Fifty-five patients, who had undergone aortic valve replacement at Miyazaki University Hospital between April 2008 and May 2011, were included in this study. The maximum diameter of the sizing tool that could be inserted into the left ventricle through the annulus had been predicted, based on the diameter measured by each modality. Agreement with surgery and each imaging modality, namely transthoracic echocardiography, multidetector computed tomography and contrast angiography, were compared using Bland-Altman analysis. RESULTS The predicted aortic annulus diameter, based on the diameter measured by transthoracic echocardiography, multidetector computed tomography and contrast angiography, was 20.3 ± 2.50, 23.9 ± 3.19, and 23.5 ± 3.55 mm, respectively, whereas, the diameter measured at surgery was 23.7 ± 2.99 mm. Predicted aortic annulus diameter measured by multidetector computed tomography best agreed with that measured at surgery. CONCLUSION We conclude that the aortic annulus diameter, measured by multidetector computed tomography, is the best modality to measure the aortic annulus diameter.
Cultivation Management: System of Rice Intensification (SRI) for Higher Production

Abstract — Enhancing farm production through an application of sustainable agriculture innovation to the existing farm system is relevant to face the simultaneous challenge in achieving food security, land protection and soil fertility and improving the wellbeing of farmers especially in rural areas. The System of Rice Intensification (SRI) technique is one of the sustainable rice cultivation techniques that have been introduced with the aim of improving the lives of rural farmers in Malaysia. The study was carried out to examine the differences in the cost of operations, paddy production and profitability of farmers using SRI technique and farmers who use conventional technique. Cost and production analysis among farmers as rice producers are important to be highlighted because farmers are the main actor in rice industry supply chain. In order to improve rice industry supply chain, focus should be given to the farmer’s welfare. Profitability analysis using budget technique has been used in this study. The study found that SRI technique is very successful in increasing the productivity of rice production while reducing the cost of production thereby increasing the profitability of farmers. It is important to identify the economic benefits of using SRI technique as it will encourage the adoption of this technique among rural areas farmers. Keywords— Supply chain, SRI practice, Cost and Benefit, SRI Practice, Innovation
Integrating True Short Stories into English Classes: The Case of Foundation Students in Oman.

Searching for practical ways to improve students’ English language skills is a real concern for all English teachers. There is a consensus among ELT practitioners regarding the significance of reading for learning new languages, since reading gives depth to language learning (Stern, 2001). Thus, teachers are obligated to provide their students with interesting and suitable texts to read. Real stories are by far more interesting and involving than scientific and historical texts. The present study aimed to investigate students’ perceptions of reading true short stories and its benefits. The study data were collected through a survey and participant observation of 19 level D students in Oman. The study findings indicated that using stories during English class was an interesting experience and had good potential as a tool to improve English language skills. The meaningful context created by the true short stories made it much easier for the teacher to conduct and run the class.
New frame for financial risk management by using hidden Markov models

Traditional time series analysis methods such as Autoregressive Moving Average Models or known as ARMA Family Models are limited by the requirement of stationary of the time series and normality and independence of the residuals. Moreover, traditional time series analysis methods are unable to identify complex (no periodic, nonlinear, irregular, and chaotic) characteristics because they attempt to characterize and predict all-time series observations. There are three major difficulties about accurate forecast of financial time series; (1) The patterns of financial time series are dynamic, i.e. there are no single fixed models that work all the time; (2) An efficient system must be able to adjust its sensitivity as time goes by; (3) Misleading information must be identified and eliminated. Thus, a Hidden Markov Model (HMM) aims to solve these problems. In HMM, instead of combining each state with an output (transition matrix), each state is associated with a probabilistic function. At time t, an observation is generated by probabilistic function, which is associated with state j, with the probability. Unlike the Markov chain, the HMM has different strategies depending on expertise. The model picks the best overall sequence of strategies based on an observation sequence. The main objective of this study is to improve the portfolio management process by incorporating technique to rotating the stocks of optimal portfolio by using HMM.
Electrode reduction using ICA and PCA in P300 Visual Speller Brain-Computer Interface system

Brain-Computer Interface (BCI) research aims at developing systems helping disabled people hereafter called subjects. Due to the fact that technology underlying BCI is not yet mature enough and still having shortcomings for usage out of laboratory, these prevent their widespread application. These shortcomings are caused by limitations in functionality of BCI system tools and techniques. The motivation of this work was to develop efficient BCI techniques including signal processing, feature extraction, pattern recognition and classification to improve the performance of P300 Visual Speller BCI system. Data sets used in this paper were acquired using BCI2000's P300 Speller paradigm provided by BCI competitions. Primarily, in the processing phase time domain and spatial domain feature extraction were applied. Followed by classification phase where various linear and extended linear classifiers were utilized. One of the main achievements of this paper is applying Independent Component Analysis (ICA) or Principal Component Analysis (PCA) as spatial domain feature extraction for dimensionality and artifact reduction. Reducing electrodes to half its original size highly improved performance with linear classifiers and yet outperformed the results of BCI competition winners with extended linear classifiers.
Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates

BACKGROUND: Pathogen contamination, causing transfusion‐transmitted diseases, is an ongoing concern in transfusion of cellular blood products. In this explorative study, the pathogen‐inactivating capacity of UVC irradiation in platelet (PLT) concentrates was investigated. The dose dependencies of inactivation of several viruses and bacteria were compared with the effect on PLT quality.