Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation of human pluripotent stem cells to retinal pigmented epithelium in defined conditions using purified extracellular matrix proteins

A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age‐related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC‐RPEs) and iPSCs (iPSC‐RPEs) express essential RPE markers and can rescue visual function in animal models. However, standard differentiation protocols yield RPE cells at low frequency, especially from iPSC lines, and the common use of Matrigel and xenogeneic feeder cells is not compatible with clinical applications. The extracellular matrix (ECM) can affect differentiation, and therefore changes in ECM composition may improve the frequency of stem cell‐RPE differentiation. We selected several purified ECM proteins and substrates, based on the in vivo RPE ECM environment, and tested their ability to support iPSC‐RPE differentiation and maintenance. iPSCs differentiated on nearly all tested substrates developed pigmented regions, with Matrigel and mouse laminin‐111 supporting the highest pigmentation frequencies. Although iPSC‐RPEs cultured on the majority of the tested substrates expressed key RPE genes, only six substrates supported development of confluent monolayers with normal RPE morphology, including Matrigel and mouse laminin‐111. iPSCs differentiated on mouse laminin‐111 produced iPSC‐RPEs expressing RPE proteins, and hESCs differentiated on mouse laminin‐111 resulted in high yields of functional hESC‐RPEs. This identification of key ECM proteins may assist with future scaffold designs and provide peptide sequences for use in synthetic, xeno‐free, GMP‐compliant generation of RPE from human pluripotent stem cells relevant to clinical translation. Copyright © 2012 John Wiley & Sons, Ltd.
An analytical framework for the design of intelligent algorithms for adaptive-rate MPEG video encoding in next-generation time-varying wireless networks

Adaptive rate video encoding is required to maximize efficiency when wireless links are involved in the communication. In fact, wireless channels are characterized by high, time-varying bit error rates. To cope efficiently with this problem adaptive forward error correction schemes have been proposed. These schemes introduce an amount of redundancy dependent on the channel conditions. Accordingly, the bandwidth available at the application layer changes: it increases when channel conditions improve, and decreases when channel conditions worsen. Obviously, the encoding parameters must be tuned to adapt the video source transmission rate to the available bandwidth. This adaptation is achieved by means of appropriate feedback laws, which are relationships between the encoding parameters to be used and other variables representing the state of the system. An analytical framework is introduced which can be used for the design of the feedback laws. To this purpose both the channel and the video source are modeled by means of Markov models. The resulting model of the whole system is denoted as SBBP/SBBP/1/K. Analysis is derived which allows to evaluate the most significant performance measures and, therefore, to design optimal feedback laws.
Subsumption & economic preference expression: an agent-based computational architecture for principled exploratory applications

This work focuses on the investigation of economic preferences, particularly within economic systems, using agent-based models (ABMs). Economic systems are a challenging area of research, exhibiting complex adaptive, non-linear, recursive properties. ABMs are now relatively widely used in economics as experimental tools across many economic schools. While these schools are presented as distinct theoretical frameworks, typical experimental approaches are strikingly similar: quantitatively rigorous, highly abstracted models of core preferences and economic behaviours are typically bundled into centralised structures and other behaviours ignored. Vast amounts of data are potentially available from computational models making validation & verification of experimental results problematic. Researchers have relied on replication of time series artefacts yielding little explanatory value, rather than examining agent behaviours themselves. To date relatively little effort has been made to codify, or critically discuss experimental protocols around these models; to verify and replicate findings; or to develop realistic validation metrics. This is a failing in the literature limiting the value of ABM approaches and leaving them open to criticism. This thesis directly addresses these issues from a practical standpoint, presenting discussion of what approaches are appropriate and what features robust methodologies should exhibit. Situation is presented as a basic validation metric, using agent-level performance measures and exploratory tools for verification and validation. Risk-adjusted, agent-level population relative performance measures are developed and tested on a typical agent-based artificial financial market (AFM) demonstrating their effectiveness, while highlighting potential methodological issues and confirming the importance of agent-level exploration alongside other validation and verification methods. The case for an overall modelling framework based around a subsumptive metaheuristic, population-based architecture is presented and discussed. In this framework, the SHaaP architecture, core preferences, preference modifying behaviours, and structural modifiers are unbundled so that they can be investigated systematically, while potentially being subsumed into larger, sophisticated non-linear preference structures. A functional SHaaP architecture is developed & implemented as part of the research. A larger case study examining the role of heuristic preference modifying behaviours in economic agent behaviours is presented, also demonstrating the architecture in operation and exploring its dynamics. Heuristic preference modifiers are widely observed in real economic entities and systems: they have a potentially critical role in regulation & risk management under
Constraint Management and Checking in Template-Based Circuit Designs

In a template-based design methodology, constraint management and proof are critical to accurate circuit analysis. Constraints are defined in one of three places: at the template level, at the circuit design level, or at the RTL level. Constraints are used to restrict the patterns of both logical and electrical analyses. At the circuit level, where the templates are instantiated, the constraints must be proven true to validate the logical and electrical analyses. In this paper, we show all aspects of our constraint management in our template-based design methodology. We show how we use constraints for formal equivalence checking, electrical analysis, and template verification and how we validate constraints using formal techniques and simulation assertions.
Mathematics and Science Learning Opportunities in Preschool Classrooms

Research Findings: The present study observed and coded instruction in 65 preschool classrooms to examine (a) overall amounts and (b) types of mathematics and science learning opportunities experienced by preschool children as well as (c) the extent to which these opportunities were associated with classroom and program characteristics. Results indicated that children were afforded an average of 24 and 26 min of mathematics and science learning opportunities, respectively, corresponding to spending approximately 25% of total instructional time in each domain. Considerable variability existed, however, in the amounts and types of mathematics and science opportunities provided to children in their classrooms; to some extent, this variability was associated with teachers' years of experience, teachers' levels of education, and the socioeconomic status of children served in the program. Practice or Policy: Although results suggest greater integration of mathematics and science in preschool classrooms than previously established, there was considerable diversity in the amounts and types of learning opportunities provided in the preschool classrooms. Affording mathematics and science experiences to all preschool children as outlined in professional and state standards may require additional professional development aimed at increasing preschool teachers' understanding and implementation of learning opportunities in these 2 domains in their classrooms.
Business history and operations management

Operations management is a key function in the modern organisation and an important area of study in the business school. Like many subjects it remains separated from the business history community. The practice of operations management can gain meaningful and significant lessons from proper consideration of the historical antecedents of current practices. Unfortunately, more than any other business area, operations management has a habit of forgetting the lessons of the past and ‘reinventing the wheel’. The purpose of this paper is to emphasise the value of historical analysis in operations management, assess the level of historical coverage of the development of operations within that subject area (taking a review of OM textbooks as a proxy), and highlight the valuable opportunities for the business history community to engage with their operations colleagues to better guide the next generation of operations management education and practice.
Inhibition of TRPM8 Channels Reduces Pain in the Cold Pressor Test in Humans

The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia.
Integrative approach for prioritizing cancer genes in sporadic colon cancer

The current multistep carcinogenesis models of colon cancer do not fully capture the genetic heterogeneity of the disease, which is additionally complicated by the presence of passenger and driver genetic alterations. The aim of this study was to select in the context of this significant heterogeneity additional genes functionally related to colon cancer development. High‐throughput copy number and gene expression data of 36 microsatellite stable sporadic colon cancers resected from patients of a single institution characterized for mutations in APC, KRAS, TP53 and loss of 18q were analyzed. Genes whose expression correlated with the underlying copy number pattern were selected, and their association with the above listed mutations and overall survival was evaluated. Gain of 20q was strongly associated with TP53 mutation, and overall survival with alterations on 7p, 8p, 13q, 18q, and 20q. An association with 18q loss and gain of 8q24 was also observed. New candidate genes with a potential role in colon cancer are PLCG1 on 20q, DBC1 on 8q21, and NDGR1 on 8p24. In addition, an unexpected pattern of loss and mutability was found in the region upstream of the KRAS gene. By integrating copy number alterations with gene expression and mutations in colon cancer associated genes, we have developed a strategy that identifies previously known molecular features and additional players in the molecular landscape of colon cancer. © 2009 Wiley‐Liss, Inc.
Polynomial Lyapunov function based stability analysis of microgrid

In this paper, a non-conventional approach to the stability analysis of a microgrid is outlined. Instead of using prevalent small-signal analysis based approaches, with predictions typically limited to the vicinity of the equilibrium, the outlined approach provides a sense of global/semi-global stability. This methodology, based on polynomial Lyapunov function based approach, is outlined below. Effectiveness of the approach are demonstrated using couple of case studies.
Information shares in Canadian agricultural cash and futures markets

This paper examines the information shares in four pairs of Canadian agricultural cash and futures markets by exploring their cointegrating relationships. Using error correction models (ECMs) and Hasbrouck's econometric method of estimating information shares, the results show that the price discovery process is most pronounced in the futures market. The identification and quantification of the dominant market of price discovery is of great interest to both hedgers and speculators. The advantage of Hasbrouck's technique is that it facilitates the quantification of the concept of price discovery and market dominance.
Analysis of the p53 gene by PCR-SSCP in ten cases of Wilms' tumor.

CONTEXT Mutations of the p53 tumor suppressor gene are the most frequent alterations observed in human neoplasias affecting adults. In pediatric oncology, however, they have seldom been identified. Wilms' tumor is a renal neoplasia commonly occurring in children and is associated with mutations of the WT1 gene. The correlation between Wilms' tumor and alterations of the p53 gene has not been well established, with a low frequency of mutations having been reported in this type of tumor. Mutation may be associated with advanced stage disease and unfavorable histology. OBJECTIVE To screen for mutations of the p53 gene by the PCR-SSCP method and DNA sequencing in cases of Wilms' tumor sug-gestive of mutation. DESIGN Case Report. CASE REPORT Evaluations of exons 5-9 of the p53 gene in DNA samples extracted by PCR-SSCP from 10 Wilms' tumors in children at different stages, and DNA sequencing. Changes in SSCP analy-sis were observed in exon 8 in two samples. The probable muta-tions were not confirmed by DNA sequencing. The absence of point mutations in p53 gene observed in the 10 samples of Wilms' tumor studied agrees with literature data, with DNA sequencing being of fundamental importance for the confirmation of possible mutations.
A Strong Association Between Down-Regulation of HLA-DR Expression and the Late Mortality in Patients with Severe Acute Pancreatitis

OBJECTIVES:There is no reliable parameter to predict the late mortality of patients with severe acute pancreatitis though it is an important issue. Recently a proposed parameter for “immunoparalysis,” a down-regulation of Human Leukocytes Antigens-DR (HLA-DR) expression on monocytes, had been detected in patients with severe but not mild acute pancreatitis. However, the relationship between this parameter and late mortality of acute pancreatitis is still unclear. Therefore, we conducted this study in order to elucidate this issue.METHODS:Twenty-five patients of severe acute pancreatitis admitted to Chang-Gung Memorial Hospital were successively enrolled during the period of 1999–2002. The HLA-DR expression, and serum levels of interleukin-10 (IL-10) and tumor necrosis factor-α(TNF-α) at different time points were measured. The HLA-DR expression was evaluated by flow cytometry and the levels of IL-10 and TNF-α were measured by ELISA.RESULTS:In our series, there were 7 (28%) late mortality cases out of 25 patients with severe acute pancreatitis. When analyzing the serial change of HLA-DR expression, it is clear that in survival group the HLA-DR expression was gradually up-regulated and in late mortality group it was persistently down-regulated (p < 0.001). When comparing with other parameters like Acute Physiological and Chronic Health Evaluation II and Ranson's score by Cox hazards model, the HLA-DR expression on 10th day (HLA-DR-10) gave the only statistically significant correlation with late mortality (p= 0.001). Furthermore, HLA-DR10 is also a good predictor for late mortality when analyzed by receiver-operating characteristics (ROC) curves with 0.944 area under ROC (AUROC) value. The optimal cutoff value of HLA-DR on 10th day for predicting late mortality was 52.3% with 94.4% sensitivity and 85.7% specificity. As for the serum levels of TNF-α and IL-10, there were significant persistently higher levels in late mortality group than in survival group (p < 0.05). Furthermore, these monocytes from severe acute pancreatitis were with partial restoration of HLA-DR expression but with normal TNF-α and IL-10 secretion ability when stimulated in vitro with LPS.CONCLUSIONS:In severe acute pancreatitis, there was a strong association between the persistent down-regulation of HLA-DR expression and the late mortality. Furthermore, a cutoff value of 52.3% of HLA-DR expressed monocytes on the 10th hospitalization day is a good predictor for late mortality in patients with severe acute pancreatitis.
The Role of Regulation, Fiscal Incentives and Changes in Tastes in the Diffusion of Unleaded Petrol

This paper analyses the diffusion of unleaded petrol in the UK. Changes in the market share of unleaded fuel are the result of changes in the composition of the car stock and changes in the choice of fuel given the car stock. We find that fuel type choices have been mainly driven by changes in tastes and learning as opposed to changes in relative prices induced by fiscal incentives. However car stock composition effects dominate the diffusion process and we find that through this route regulatory changes have made major contributions to changes in the market share of unleaded fuel.
Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia major.

BACKGROUND Beta-thalassemia major is one of the most frequent hemoglobinopathies in the world. This is a study on the levels of prooxidant-antioxidant balance (PAB) that can measure the pro-oxidant burden and the anti-oxidant capacity simultaneously in one assay, giving a redox index, as well as an assessment of high-sensitivity C-reactive protein (hs-CRP) in patients with beta-thalassemia major. It also determines the impact both on kidney function tests. METHODS Ninety subjects with beta-thalassemia major (betaTM) and 90 more healthy subjects as the control group were enrolled in the study. Laboratory parameters, serum hs-CRP, and the novel assay of prooxidant-antioxidant balance were measured. RESULTS Biochemical and hematological variables, except MCHC, were significantly decreased in patients. Ferritin (p < 0.001) and PAB (p < 0.001) values were statistically increased in patients, whereas hs-CRP (p > 0.05) did not significantly increase in patients. Spearman's correlation univariate analysis showed no significant correlation between PAB with hs-CRP or ferritin. However, there was a significant statistical correlation between hs-CRP with creatinine and triglycerides. Also we found a slight and negative correlation between high-density lipoprotein cholesterol, hemoglobin, and hemotocrit with inflammatory factor. CONCLUSIONS Briefly, we found higher levels of PAB values and a slight increase in hs-CRP concentration in patients, which may be involved in the pathological consequences of beta-thalassemia major and contribute to the gradual development of injury to the organs.
Mass selective gas phase study of ClO, OClO, ClOO and ClAr by anion-ZEKE-photoelectron spectroscopy

Anion-ZEKE-photoelectron spectra of ClO-, OClO-, ClOO- and the van der Waals cluster ArCl- have been measured. Refined or new values for the electron affinity of ClO, OClO and ClOO have been found. The peak positions in these spectra are in very good agreement with former ClO- and OClO- anion-photoelectron spectra (K. M. Gilles, M. L. Polak and W. C. Lineberger, J. Chem. Phys., 1992, 96, 8012) and a recent ArCl- anion-ZEKE spectrum (T. Lenzer, I. Yourshaw, M. Furlanetto, G. Reiser and D. Neumark, J. Chem. Phys., 1992, 110, 9578). The higher resolution of our anion-ZEKE-photoelectron spectrum of OClO- led to a refined assignment of the corresponding anion-photoelectron spectrum. In addition, a strong difference in the relative intensities of the vibrational peaks has been found in the anion-ZEKE-spectrum of OClO- in comparison with the anion-photoelectron spectrum. For the first time, mass selective spectroscopic information has been obtained for ClOO. The strong similarity to the ArCl- spectrum indicates a weakly bound van der Waals cluster Cl.O2. Binding energies of the anion, neutral ground and neutral excited state could be deduced. These are in good agreement with the electron affinities of Cl and ClOO, but differ from theoretical values (K. A. Peterson and H. J. Werner, J. Chem. Phys., 1992, 96, 8948) by a factor of 4.5 and from thermochemically determined values (J. M. Nicovich, K. D. Kreutter, C. J. Shackelford and P. H. Wine, Chem. Phys. Lett., 1991, 179, 367 and S. Baer, H. Hippler, R. Rahn, M. Siefke, N. Seitzinger and J. Troe, J. Chem. Phys., 1991, 95, 6463) by a factor of 9.
Common Throughput Maximization in UAV-Enabled OFDMA Systems With Delay Consideration

The use of unmanned aerial vehicles (UAVs) as communication platforms is of great significance in future wireless networks, especially for on-demand deployment in temporary events and emergency situations. Although prior works have shown the performance improvement by exploiting the UAV’s mobility, they mainly focus on delay-tolerant applications. As delay requirements fundamentally limit the UAV’s mobility, it remains unknown whether the UAV is able to provide any performance gain in delay-constrained communication scenarios. Motivated by the above, we study, in this paper, an UAV-enabled orthogonal frequency-division multiple access (OFDMA) network where an UAV is dispatched as the mobile base station (BS) to serve a group of users on the ground. We consider a minimum-rate ratio (MRR) for each user, defined as the minimum instantaneous rate required over the average achievable throughput, to flexibly adjust the percentage of its delay-constrained data traffic. Under a given set of constraints on the users’ MRRs, we aim to maximize the minimum average throughput of all users by jointly optimizing the UAV trajectory and OFDMA resource allocation. First, we show that the max–min throughput in general decreases as the users’ MRRs become larger, which reveals a fundamental throughput-delay tradeoff in UAV-enabled communications. Next, we propose an iterative parameter-assisted block coordinate descent method to optimize the UAV trajectory and OFDMA resource allocation alternately, by applying the successive convex optimization and the Lagrange duality, respectively. Furthermore, an efficient and systematic UAV trajectory initialization scheme is proposed based on the simple circular trajectory. Finally, simulation results are provided to verify our theoretical findings and demonstrate the effectiveness of our proposed designs.