Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced T cell receptor gene therapy for cancer

Importance of the field: Adoptive therapy with T cell receptor- (TCR-) redirected T cells has shown efficacy in mouse tumor models and first responses in cancer patients. One prerequisite to elicit effective anti-tumor reactivity is the transfer of high-avidity T cells. Their generation, however, faces several technical difficulties. Target antigens are often expressed at low levels and their recognition requires the use of high-affine receptors. Yet, mainly low-affine TCRs have been isolated from tumor-infiltrating lymphocytes. Furthermore, upon transfer into a T cell the introduced receptor has to compete with the endogenous TCR. Areas covered in this review: This review discusses how the functional avidity of TCR-modified T cells can be enhanced by i) increasing the amount of introduced TCR heterodimers on the cell surface; and ii) generating receptors with high affinity. Risks of TCR gene therapy and possible safety mechanisms are discussed. What the reader will gain: The reader will gain an overview of the technical developments in TCR and T cell engineering. Take home message: Despite technical obstacles, many advances have been made in the generation of high-avidity T cells expressing enhanced TCRs. Mouse studies and clinical trials will evaluate the effect of these improvements.
Reliability of the Canadian Occupational Performance Measure in patients with ankylosing spondylitis.

OBJECTIVE The Canadian Occupational Performance Measure (COPM) is a client-centered measure, designed to detect changes in occupational performance over time. The main aim of our study was to examine the test-retest reliability of the Norwegian version of the COPM in patients with ankylosing spondylitis (AS) in 3 different retest modes of data collection. METHODS A total of 119 patients with AS completed the baseline COPM interview before randomization into one of 3 modes of retest data collection performed 2 weeks later: by personal interview, telephone interview, or mailed questionnaire. Scores were computed for Performance and Satisfaction, and the 2 sets of scores were examined for reliability by intraclass correlations (ICC), and by the Bland-Altman procedure for calculation of smallest detectable difference (SDD). RESULTS The ICC coefficients for Performance and Satisfaction were as follows: 0.92 and 0.93 (rescoring by personal interview), 0.73 and 0.73 (rescoring by telephone interview), and 0.90 and 0.90 (rescoring by mail). SDD for the Performance and Satisfaction scores were 1.47 and 1.80, respectively, for rescoring by personal interview; 3.14 and 4.00 for rescoring by telephone interview; and 2.20 and 2.41 for rescoring by mailed survey. CONCLUSION The results confirm that the COPM is a reliable instrument for use in clinical practice in patients with AS, and may serve as an instrument to promote a patient-centered approach in the planning and evaluation of rehabilitation programs. Mailed questionnaires may replace personal interview in followup examinations, while rescoring by telephone interview is less reliable.
Economic growth in Iran through labor productivity growth

Economic growth is a fundamental measurement to assess a country's performance and productivity. For this reason, growth and productivity are in policy agenda of many countries especially success economic countries. Based on some studies and reports (e.g., those by UK parliament, 2016; OECD, 2012), labor productivity in developed countries is analyzed and considered as a secondary economic growth. In this study, we investigated the relationship between economic growth and change of labor productivity in Iran and their challenges. Our object was to answer to two questions: 1) Is any relationship between level of GPD and labor productivity in Iran? ; 2) What are the driving forces (effective factors) behind the growth of labor productivity? To answer to question 1, economic data from national and international information bank gathered. Relation between GDP and labor productivity examined by calculating some ratios and finally, trends and behavioral patterns analyzed. Patterns drew on Iran? s economic status compared with 10 other countries in regional category (such as USA, Japan, Turkey, and France). Therefore, the study findings revealed that there is a direct relationship between GDP and labor productivity In Iran. To answer to the question 2, initially we developed a conceptual model based on theories and considered labor productivity as complex and multi-dimensional phenomenon (Economic and social dimensions) and assumed labor productivity as a function of internal (organizational) and external (environmental) factors. According to find effective factors, a questionnaire based on conceptual model designed and before evaluating the reliability and validity of questionnaire, it reviewed with 15 academic and professionals. Data collected through questionnaires that distributed to 250 managers and employees from government and non-government sectors.Structural Equation Modeling (SEM) employed, which reported significant and positive relationship between the labor productivity and driving forces such as: competitiveness, size of government sector, unemployment, corruption, social security system (external factors) and Wage/salary, work culture, employee adaptability, employee knowledge and skill, team working, performance appraisal system, career management (internal factors). Whereas, the association between labor productivity and some variables such as sex, age, post and position, sector were not supported. Eventually, challenges based on driving forces that are identified as more effective, discussed.As conclusion findings can be applied by policy makers and managers to make policies to improve labor productivity and increase economic growth rate in Iran.
Evaluation of Cortical Imaging Techniques Based on Somatosensory Evoked Potentials

In the present study we evaluate the performance of several inverse algorithms for reconstructing the cortical current density distributions from scalp EEG recordings. The direct cortical SEP recordings in a patient were used as a gold standard to assess the performance of the numerical algorithms. The present results suggest that L1-norm methods gave the most accurate results in terms of cortical current density imaging of brain responses invoked by somatosensory stimulation
The changes of hormonal serum levels and ovulation/pregnancy rates after ovarian electrocautery in microlaparoscopy and laparoscopy in patients with PCOS.

OBJECTIVES To compare the efficacy of ovarian electrocautery performed during microlaparoscopy and laparoscopy, basing on ovulation and pregnancy rates obtained within one year of follow-up. MATERIALS AND METHODS Ovarian drillings, performed with the use of endoscopic methods, were carried out in 135 women with hormonal and ultrasound features of PCOS, aged 30-39 (average age 36 +/- 3.3). Laparoscopic ovarian electrocautery was carried out in 65 cases, whereas microlaparoscopic drilling was conducted in 70 cases. The obtained results were compared in regard to duration of the procedure and ovulation/pregnancy rates within one year of follow-up. Changes in hormonal profiles were also compared in both groups, measured in patients who did not get pregnant before, and 3 months after, the procedures. RESULTS The difference in durations between the two studied procedures was statistically significant (19 +/- 3 min vs. 24 +/- 4.4 min; p<0.001). However, the ovulation and pregnancy rates did not differ significantly between the two groups (72% vs. 77.7%; p<0.5 and 19.4% vs. 20%; p<0.95, respectively). There were also similar trends in hormonal changes after microlaparoscopic and laparoscopic drilling. CONCLUSIONS The efficacy of ovarian drilling in PCOS, estimated by ovulation and pregnancy rates within 12 months of follow-up is similar for microlaparoscopy and laparoscopy, as well as the trends in hormonal changes. Ovarian electrocautery is significantly longer in microlaparoscopy, but the difference in time is of no practical impact.
Optimization of System-of-Systems architectures for maritime border control using genetic algorithms

Engineering solutions to surveillance operations in wide areas are based on the integration of manned aircrafts and Unmanned Aerial Vehicles in complex System-of-Systems (SoS) architectures. The selection of one specific architecture depends on a very large set of parameters and constraints related to the surveillance scenario, target statistics and the availability of limited resources such as electro-magnetic spectrum, crew, airfields or simply budgetary restrictions. This paper covers the use of Genetic Algorithms (GA) to obtain the best SoS architecture for a given surveillance scenario and a given set of limited resources.
Two kinds of myosin phosphatases with different enzymatic properties from fresh chicken gizzard smooth muscle. Purification and characterization.

Two kinds of myosin phosphatases were purified from fresh chicken gizzard smooth muscle. Alkaline phosphatase (CGP-a), which requires Mg2+, was most active at pH 8.6 with 2 to 4 mM Mg2+, and was essentially the same as the phosphatase we reported previously (J. Biochem. 99, 1027-1036 (1986]. On the other hand, neutral phosphatase (CGP-b), was most active at pH 7.5 with 0 to 2 mM Mg2+, and was similar to SMP-IV reported by Pato and Kerc (J. Biol. Chem. 260, 12359-12366 (1985]. Although both phosphatases showed similar Vm (4.8 to 13 mumol/mg/min) using phosphorylated myosin head as the substrate under optimal conditions, CGP-b had a smaller Km (3.7 to 6.7 microM) than CGP-a by about 4-fold. CGP-b showed a lower Vm (1.9 to 8.4 mumol/mg/min) for the isolated myosin light chain than myosin itself, while CGP-a showed rather higher Vm (17 to 32 mumol/mg/min). Although the activity of CGP-a decreased monotonically with increase of ionic strength, that of CGP-b increased slightly with increase in NaCl until 0.1 M and then decreased. Those results suggest that CGP-b may be the effective myosin phosphatase in vivo. The analysis by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate showed that both phosphatases were composed of a single polypeptide having a molecular weight of 37,000. The tetrameric structure was assumed for both phosphatases, because the molecular weight in the native state was estimated as 140,000 or 145,000 for CGP-a or CGP-b, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Reduced neuronal nitric oxide synthase is involved in ischemia‐induced hippocampal neurogenesis by up‐regulating inducible nitric oxide synthase expression

Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) ‐derived NO and inducible nitric oxide synthase (iNOS) ‐derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia‐induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7‐nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up‐regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element‐binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7‐nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia‐induced hippocampal neurogenesis by up‐regulating iNOS expression and cAMP response element‐binding protein phosphorylation.
Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study.

OBJECTIVE PREDICTIVE is a large, observational study of the empirical use of insulin detemir in patients with type 1 or type 2 diabetes (T1DM/T2DM). This post hoc analysis evaluates insulin-naïve patients with T2DM uncontrolled on oral antidiabetic drugs (OADs) who were initiated and remained on once-daily insulin detemir for 12 weeks. RESEARCH DESIGN AND METHODS This observational, multinational, multi-center, open-label prospective study evaluated the efficacy and safety of insulin detemir in 1653 insulin-naïve patients with T2DM (mean age 60.8 +/- 10.9 years, BMI 29.8 +/- 4.8 kg/m(2), and HbA(1C) 8.82 +/- 1.50%). Statistical comparisons were made between baseline and 12-week follow up data. Our study was subject to the usual limitations of observational studies. MAIN OUTCOME MEASURES Endpoints were: incidence of serious adverse drug reactions, including number of hypoglycemic events (total, major, and nocturnal), glycemic parameters, and weight change. RESULTS Following insulin initiation, no significant change occurred in the number of nocturnal hypoglycemic events or total hypoglycemic events (p = 0.4513), and no serious adverse drug reactions were observed during the 12 weeks of treatment. HbA(1C) decreased by a mean 1.25% (SD +/- 1.25%; p < 0.0001), with 30% of patients (n = 383) achieving HbA(1C) <7% at 12 weeks. Mean changes in fasting blood glucose and fasting blood glucose variability were -3.62 mmol/L (SD +/- 2.93; p < 0.0001) and -0.48 mmol/L (SD +/- 1.03; p < 0.0001), respectively. Body weight decreased by a mean 0.5 kg (SD +/- 3.3; p < 0.0001), with weight loss or no weight change occurring in a substantial percentage of patients in each BMI category (<25, 25-30, 30-35, and >35 kg/m(2)). Patients with higher baseline BMI lost the most weight, with the greatest weight loss (-1.20 kg) reported in those with BMI >35 kg/m(2). CONCLUSIONS Empirical use of insulin detemir as an insulin initiation strategy can improve glycemic control with good tolerability, including a low risk of hypoglycemia and a weight benefit, in a majority of insulin-naïve patients uncontrolled on OADs.
Promoting understanding of special education procedural safeguards through a parental workshop

By law, parents of children with disabilities must receive their Procedural Safeguards every time their student is going to be evaluated, re-evaluated, or considered for a change of disability identification or placement. Special Education teachers provide parents with a copy of Procedural Safeguards in their native language and provide an oral explanation of the safeguards. These efforts are often not enough for parents to understand their rights. This study analyzed the impact of providing a workshop on Procedural Safeguards for Spanish speaking parents. The research also examined parent's perception in regards to participation in IEPs. The results suggest that the workshop was valuable to parents. Following the workshop, the Spanish-speaking parents expressed greater self­ confidence in participating in IEP meetings and the majority appeared to have maintained information relevant to the Procedural Safeguards and IEP process.
Persistence of Human Milk Proteins in the Breast‐Fed Infant

Several proteins in human milk are postulated to have physiological functions in the breastfed infant. Therefore, survival of human milk proteins after passage through the gastrointestinal tract of the breast‐fed infant was investigated. Fecal samples were collected from exclusively breast‐fed term infants and milk samples from their mothers. Soluble proteins in the feces were extracted and analyzed for total protein, nitrogen, lactoferrin, secretory IgA, serum albumin and lysozyme. Significant amounts of lactoferrin and secretory IgA were excreted by the infants and this excretion decreased throughout the study period in a trend similar to the decreasing milk concentrations of these proteins. Gel filtration demonstrated excreted lactoferrin and secretory IgA to be intact. No serum albumin or lysozyme was detected in the fecal extracts. Crossed Immunoelectrophoresis showed three human milk proteins to be present in the feces—the third was identified as α1‐antitrypsin. Excretion of these proteins indicates the total protein content of human milk is an over‐estimation of the protein nutritionally available to the infant.
LOCAL HEDGING OF VARIABLE ANNUITIES IN THE PRESENCE OF BASIS RISK

Abstract A method to hedge variable annuities in the presence of basis risk is developed. A regime-switching model is considered for the dynamics of market assets. The approach is based on a local optimization of risk and is therefore very tractable and flexible. The local optimization criterion is itself optimized to minimize capital requirements associated with the variable annuity policy, the latter being quantified by the Conditional Value-at-Risk (CVaR) risk metric. In comparison to benchmarks, our method is successful in simultaneously reducing capital requirements and increasing profitability. Indeed the proposed local hedging scheme benefits from a higher exposure to equity risk and from time diversification of risk to earn excess return and facilitate the accumulation of capital. A robust version of the hedging strategies addressing model risk and parameter uncertainty is also provided.
Nuclear distribution of the Ki-67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells.

It has been claimed that the commercially available Ki-67 monoclonal antibody recognizes a nuclear antigen which is solely expressed in cycling cells. Therefore, at present, Ki-67 is increasingly used as a tool in evaluating growth fractions (GFs) of human tumors. Here we describe specific patterns in the expression and topological distribution of this antigen during the cell cycle in MCF-7 human breast cancer cells. Our results support earlier findings that the antigen belongs to a class of antigens associated with the structural organization of meta- and anaphase chromosomes, and proteins located near the cortical regions of prenucleolar bodies and nucleoli. Using 5'-bromodeoxyuridine-labeling technology, we show that the expression may be undetectably low at the onset of DNA replication. Comparison of Ki-67 fractions (KFs) and GFs as estimated from continuous 5'-bromodeoxyuridine-labeling curves revealed that KF was invariably higher than GF: in exponentially growing cov362.c14 human ovary cancer cells, KF was only 3.5% higher than GF; in MCF-7 cells, 11.3 +/- 4.6%. In MCF-7 cultures either growing under suboptimal conditions or treated with 10(-6) M tamoxifen, the difference was more pronounced. Furthermore, we evaluated the decrease of Ki-67-positive cells in nutritionally deprived and cell cycle-specific, drug-treated cultures. Since the results indicate that nonproliferating cells may retain the antigen for a considerable period of time, KF may not always be a reliable indicator of GF.
Hot-Melt Coating Technology. I. Influence of Compritol® 888 Ato and Granule Size on Theophylline Release

The aim of this work was to study the influence of theophylline granule size and the percentage of Compritol® 888 Ato on in vitro drug release from granules and tablets. The granules were coated in a fluidized bed apparatus. The dissolution profiles of these granules differed from those of granules coated with classical agents, and there were also differences between the various sieve fractions studied. Drug release was characterized by a rapid-release phase, followed by a slow-release phase. Results indicate that theophylline release can be controlled by controlling granule size. Inspection of the appearance of the tablets at the end of the dissolution test revealed that all tablets containing Compritol 888 Ato remained intact. This indicated that the Compritol 888 Ato used in the tablet formulation created an inert matrix through which the drug diffused. It was found that the Higuchi relationship of linear square root of time was the best model to describe the release kinetics of the drug from tablets. This also confirmed that a matrix diffusion-controlled mechanism was operative. Given the difference between the dissolution profiles of the granules and the tablets, it was concluded that this matrix is formed during compression.
Genetic and genomic evidence of niche partitioning and adaptive radiation in mountain pine beetle fungal symbionts

Bark beetles form multipartite symbiotic associations with blue stain fungi (Ophiostomatales, Ascomycota). These fungal symbionts play an important role during the beetle's life cycle by providing nutritional supplementation, overcoming tree defences and modifying host tissues to favour brood development. The maintenance of stable multipartite symbioses with seemingly less competitive symbionts in similar habitats is of fundamental interest to ecology and evolution. We tested the hypothesis that the coexistence of three fungal species associated with the mountain pine beetle is the result of niche partitioning and adaptive radiation using SNP genotyping coupled with genotype–environment association analysis and phenotypic characterization of growth rate under different temperatures. We found that genetic variation and population structure within each species is best explained by distinct spatial and environmental variables. We observed both common (temperature seasonality and the host species) and distinct (drought, cold stress, precipitation) environmental and spatial factors that shaped the genomes of these fungi resulting in contrasting outcomes. Phenotypic intraspecific variations in Grosmannia clavigera and Leptographium longiclavatum, together with high heritability, suggest potential for adaptive selection in these species. By contrast, Ophiostoma montium displayed narrower intraspecific variation but greater tolerance to extreme high temperatures. Our study highlights unique phenotypic and genotypic characteristics in these symbionts that are consistent with our hypothesis. By maintaining this multipartite relationship, the bark beetles have a greater likelihood of obtaining the benefits afforded by the fungi and reduce the risk of being left aposymbiotic. Complementarity among species could facilitate colonization of new habitats and survival under adverse conditions.
Workload Characterization

Analyzing an e-commerce site's scalability requires a solid understanding of its workload characteristics, but this characterization must occur at multiple levels and time scales. The author and colleagues have performed several workload characterization studies, including auction sites. Here, I present the general method we adopted and a few examples of the workload characterizations we studied.