Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of telomere length and homeostasis by telomerase enzyme processivity

Summary Telomerase is a ribonucleoprotein consisting of a catalytic subunit, the telomerase reverse transcriptase (TERT), and an integrally associated RNA that contains a template for the synthesis of short repetitive G-rich DNA sequences at the ends of telomeres. Telomerase can repetitively reverse transcribe its short RNA template, acting processively to add multiple telomeric repeats onto the same DNA substrate. The contribution of enzyme processivity to telomere length regulation in human cells is not well characterized. In cancer cells, under homeostatic telomere length-maintenance conditions, telomerase acts processively, whereas under nonequilibrium conditions, telomerase acts distributively on the shortest telomeres. To investigate the role of increased telomerase processivity on telomere length regulation in human cells with limited lifespan that are dependent on human TERT for lifespan extension and immortalization, we mutated the leucine at position 866 in the reverse transcriptase C motif of human TERT to a tyrosine (L866Y), which is the amino acid found at the equivalent position in HIV-1 reverse transcriptase. We report that, similar to the previously reported gain-of-function Tetrahymena telomerase mutant (L813Y), the human telomerase variant displays increased processivity. Human TERT-L866Y, like wild-type human TERT, can immortalize and extend the lifespan of limited-lifespan cells. Moreover, cells expressing human TERT-L866Y display heterogenous telomere lengths, telomere elongation, multiple telomeric signals indicative of fragile sites and replicative stress, and an increase in short telomeres, which is accompanied by telomere trimming events. Our results suggest that telomere length and homeostasis in human cells may be regulated by telomerase enzyme processivity.
Dimensions of poverty measurement

In December 2012 the Office of the Children’s Commissioner produced a report on Solutions to Child Poverty in New Zealand: evidence for action (Expert Advisory Group on Solutions to Child Poverty, 2012a, 2012b). This wide-ranging report provided a detailed analysis of the causes and consequences of child poverty, as well as providing a range of policy solutions to the various dimensions of child poverty. Recommendations were not limited to just increasing the level of disposable income for poor households: the report also made policy recommendations in relation to health care, housing costs and standards, educational attainment,
An Android-based testbed for hybrid Wireless Mesh Networks in the IoT perspective

Thanks to the widespread use of wireless systems with the Android operating system, the presence of intelligent devices that can access the network is increasingly high. Wireless Mesh Networks are proposed today as the enabling technology to increase even more the pervasiveness of the Internet access and as a alternative to overcome typical limitations of existing infrastructure, but there have not been so far substantial contributions about the integration of different technologies. Furthermore, nowadays heterogeneous networks are a promising reality; a seamless integration of different technologies would leverage them to a key element to increase pervasiveness of access and connectivity in the emerging view of the Internet of Things. In this perspective the present paper proposes an open source implementation of an ad-hoc network based on mobile devices running Android, along with its integration with the infrastructured network, in an IPv4/IPv6 dual stack environment. The use of commercial devices for the end-user terminals and the leverage of the infrastructured network on widely used routing protocols enable this solution to be easily deployable in the real world. The developed test bed provides a novel and flexible framework for validation of networking solutions in emerging scenarios with heterogeneous network components.
PROSO II – a new method for protein solubility prediction

Many fields of science and industry depend on efficient production of active protein using heterologous expression in Escherichia coli. The solubility of proteins upon expression is dependent on their amino acid sequence. Prediction of solubility from sequence is therefore highly valuable. We present a novel machine‐learning‐based model called PROSO II which makes use of new classification methods and growth in experimental data to improve coverage and accuracy of solubility predictions. The classification algorithm is organized as a two‐layered structure in which the output of a primary Parzen window model for sequence similarity and a logistic regression classifier of amino acid k‐mer composition serve as input for a second‐level logistic regression classifier. Compared with previously published research our model is trained on five times more data than used by any other method before (82 000 proteins). When tested on a separate holdout set not used at any point of method development our server attained the best results in comparison with other currently available methods: accuracy 75.4%, Matthew’s correlation coefficient 0.39, sensitivity 0.731, specificity 0.759, gain (soluble) 2.263. In summary, due to utilization of cutting edge machine learning technologies combined with the largest currently available experimental data set the PROSO II server constitutes a substantial improvement in protein solubility predictions. PROSO II is available at http://mips.helmholtz‐muenchen.de/prosoII.
Cultures In Our Community A Social Studies Unit

CULTURES IN OUR COMMUNITY A SOCIAL STUDIES UNIT By Anna Louise Buglino May 2010 The purpose of this project was to create a yearlong unit for social studies that any teacher could pick up and implement into their classroom. It was designed using second grade standards, but can be modified for use in other grade levels. The units are integrated into all subject areas with the goal of teaching students about the community in which they live. It also was designed to create in the classroom an understanding of cultures different from their own. This will create a deeper understanding and awareness of diverse populations and their differences. The instruction of social studies education in the United States was also explored in this project. It looks at the history of social studies education starting in 1916 and moves to the present day. It then discusses the value of teaching social studies today, which is primarily citizenship development. Finally, it goes through the methods that have been seen to be most effective in meeting this goal.
Class-dependent, non-convex losses to optimize precision

Retrieving a small set of relevant and interesting objects from a large background class is challenging because classifiers can easily be overwhelmed by the large class. Classifiers have been developed that are more sensitive to the small class, and typically they optimize a ranking, or precision at the top. These measures can be costly because they often look at pairwise rankings. The classical approach of just reweighing the relevant objects also has its limits because the influence of outliers and mislabeled objects also dramatically increases, deteriorating the performance. In this paper we propose an alternative solution that uses non-convex and class dependent loss functions. The non-convex loss makes the classifier less sensitive to outliers, while the class-dependent loss stresses the interesting class. It can not only be used to solve retrieval problems, but also classification problems in which not all objects are labeled reliably, like in Multiple Instance Learning or Positive and Unlabeled data learning. For Multiple Instance Learning and learning from Positive and Unlabeled data it is even shown that these non-convex, class-dependent losses are already implicitly used.
Salmonella Utilizes d-Glucosaminate via a Mannose Family Phosphotransferase System Permease and Associated Enzymes

ABSTRACT Salmonella enterica is a globally significant bacterial food-borne pathogen that utilizes a variety of carbon sources. We report here that Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) uses d-glucosaminate (2-amino-2-deoxy-d-gluconic acid) as a carbon and nitrogen source via a previously uncharacterized mannose family phosphotransferase system (PTS) permease, and we designate the genes encoding the permease dgaABCD (d-glucosaminate PTS permease components EIIA, EIIB, EIIC, and EIID). Two other genes in the dga operon (dgaE and dgaF) were required for wild-type growth of S. Typhimurium with d-glucosaminate. Transcription of dgaABCDEF was dependent on RpoN (σ54) and an RpoN-dependent activator gene we designate dgaR. Introduction of a plasmid bearing dgaABCDEF under the control of the lac promoter into Escherichia coli strains DH5α, BL21, and JM101 allowed these strains to grow on minimal medium containing d-glucosaminate as the sole carbon and nitrogen source. Biochemical and genetic data support a catabolic pathway in which d-glucosaminate, as it is transported across the cell membrane, is phosphorylated at the C-6 position by DgaABCD. DgaE converts the resulting d-glucosaminate-6-phosphate to 2-keto-3-deoxygluconate 6-phosphate (KDGP), which is subsequently cleaved by the aldolase DgaF to form glyceraldehyde-3-phosphate and pyruvate. DgaF catalyzes the same reaction as that catalyzed by Eda, a KDGP aldolase in the Entner-Doudoroff pathway, and the two enzymes can substitute for each other in their respective pathways. Examination of the Integrated Microbial Genomes database revealed that orthologs of the dga genes are largely restricted to certain enteric bacteria and a few species in the phylum Firmicutes.
Endoscopic removal of metallic airway stents.

BACKGROUND Complications of metallic airway stents include granulation tissue formation, fracture of struts, migration, and mucous plugging. When these complications result in airway injury or obstruction, it may become necessary to remove the stent. There have been few reports detailing techniques and complications associated with endoscopic removal of metallic airway stents. We report our experience with endoscopic removal of 30 such stents over a 3-year period. METHODS We conducted a retrospective review of 25 patients who underwent endoscopic stent removal from March 2001 to April 2004. The patients ranged in age from 17 to 80 years (mean, 56.3 years). There were 10 male and 15 female patients. The stents had been placed for nonmalignant disease in 20 patients (80%) and malignant disease in 5 patients (20%). All procedures were done under general anesthesia with a rigid bronchoscope. Special attention was focused on the technique of stent removal and postoperative complications. RESULTS Thirty metallic airway stents were successfully removed from 25 consecutive patients over a 3-year period. The basic method of removal involved the steady application of traction to the stent with alligator forceps. In all cases, an instrument such as the barrel of the rigid bronchoscope or a Jackson dilator was employed to help separate the stent from the airway wall before removal was attempted. In some instances, the airway wall was pretreated with thermal energy prior to stent removal. Complications were as follows: retained stent pieces (n = 7), mucosal tear with bleeding (n = 4), re-obstruction requiring temporary silicone stent placement (n = 14), need for postoperative mechanical ventilation (n = 6), and tension pneumothorax (n = 1). CONCLUSIONS Although metallic stents may be safely removed endoscopically, complications are common and must be anticipated. Other investigators have described airway obstruction and death as a result of attempted stent removal. Placement and removal of metallic airway stents should only be performed at centers that are prepared to deal with the potentially life-threatening complications.
Cardiac MR imaging to measure myocardial blood flow response to the cold pressor test in healthy smokers and nonsmokers.

PURPOSE To determine if myocardial perfusion cardiac magnetic resonance (MR) imaging can show changes in myocardial blood flow (MBF) during the cold pressor test (CPT) and can allow identification of the differing endothelial function of smokers and nonsmokers when compared during adenosine stress. MATERIALS AND METHODS The study was approved by the institutional ethics review board and all participants gave informed written consent. Twenty-nine healthy volunteers (19 nonsmokers, 10 smokers; mean age ± standard deviation, 22 years ± 4) underwent 1.5-T MR imaging and analysis. Myocardial perfusion was assessed during rest, peak CPT, and adenosine hyperemia with a saturation-recovery gradient-echo pulse sequence (spatial resolution, 2.4 × 2.4 × 10 mm). Global, endocardial, and epicardial MBF were calculated by using Fermi-constrained deconvolution. Paired and independent t test statistical analyses were used to compare the responses between tests and groups. Regression analysis was performed to identify predictors of MBF change. RESULTS MBF at rest was similar between the nonsmoking and smoking groups (0.97 mL/g/min ± 0.4 vs 0.96 mL/g/min ± 0.3, respectively; P = .96). Nonsmokers responded to CPT with a 47% increase in MBF (1.43 mL/g/min ± 0.5) and smokers responded with a 27% increase (1.22 mL/g/min ± 0.4; P < .001). An endocardial-to-epicardial gradient existed at rest (nonsmokers, 1.10 [P = .002]; smokers, 1.30 [P = .01]) and CPT (nonsmokers, 1.19 [P < .001] smokers, 1.28 [P = .04]) but reversed during adenosine stress (nonsmokers, 0.89 [P = .03]; smokers, 0.92 [P = .42]). CONCLUSION Myocardial perfusion cardiac MR imaging during CPT can allow assessment of changes in MBF globally and in the separate myocardial layers in healthy smokers and nonsmokers. This allows the combined assessment of endothelium-dependent (CPT) and endothelium-independent (adenosine stress test) MBF reserve in a single study.
The return of cities: the trajectory of Swiss cities from demographic loss to reurbanization

ABSTRACT Reurbanization refers to the new demographic growth of cities that previously lost population. How can we explain such a trend reversal? This paper discusses theoretically both phases of urban decline and reurbanization. It examines the trajectory of Swiss cities that have moved from a period of decline (1970–2000) to a new growth (since 2000). It analyses the components behind the population evolution, discusses the socio-cultural, economic and political trends triggering or enabling reurbanization, and identifies three main results. First, reurbanization is due to several population groups: the growing international mobility of the labour force, the increasing number of non-family households (in the context of the second demographic transition) and the growing attractiveness of cities for young adults (extension of youth as a life stage). Second, reurbanization is not only housing-led (construction of dwellings due to planning strategies and real estate activities). It is also population-led: A generation replacement induces a rejuvanation of the age structure and an increase in the density of occupancy of dwellings. Third, reurbanization can be broadly interpreted as a return of cities in terms of residential aspirations, political agenda and real estate activities. As a conclusion, I outline a research agenda on reurbanization.
Hematocrit and Risk of NIDDM

There is limited evidence that raised hematocrit levels may be associated with insulin resistance, which links cardiovascular disease with NIDDM. The association between hematocrit level at screening and the subsequent development of physician-diagnosed NIDDM during 12.8 years of follow-up was examined in a prospective study of 7,735 middle-aged men drawn at random from general practice in 24 British towns. With the exclusion of men with missing hematocrit data and men with diabetes at screening, data were available for 7,193 men, in whom there were 187 new cases of NIDDM during follow-up. The risk of NIDDM increased significantly with increasing hematocrit levels. There was more than a fourfold increase in relative risk (RR) of diabetes among men with a hematocrit of ≥48% relative to those with a hematocrit <42%, adjusted for age and BMI (RR 4.5; 95% CI 2.5–6.3). On further adjustment for predictors of NIDDM with which hematocrit is correlated, there remained a strong linear association with the risk of diabetes. There was a nearly fourfold increased risk of NIDDM in the highest relative to the lowest hematocrit group in the fully adjusted proportional hazard model (RR 3.6; 95% CI 1.7–7.6). The strong positive association between hematocrit level and risk of diabetes was seen even after exclusion of men with preexisting ischemic heart disease. The findings suggest that a raised hematocrit level, which is a major determinant of whole blood viscosity, should be added to the cluster of risk factors that link NIDDM with atheromatous, vascular disease.
Use and abuse of medication during 2014 FIFA World Cup Brazil: a retrospective survey

Objective To examine the use of medication of top-level male players during the 2014 FIFA World Cup Brazil. Design Retrospective survey. Participants/information 736 top level players. Setting The teams’ physicians disclosed a list of the medications used by each player within 72 h before each match of the 2014 FIFA World Cup Brazil. Outcome measures Average number of medications used per player per match or during the tournament; average number and percentage of players using at least one medication per match or during the tournament. Results 67.0% of all players took various types of medication during the tournament. The most used medications during the tournament were non-steroidal anti-inflammatory drugs (NSAIDs), by 54.2% of all players, followed by analgaesics (12.6%); β-2 agonists were only used by 0.5%. On average, 0.8 medications per player were used before each match. More players were reported taking medications during the knockout round than during the qualification round (0.36±0.48 vs 0.49±0.50, p<0.001). Players from the South American and Asian Confederations took twice as many medications per match as players from the African Confederation (1.17±1.55 and 1.01±1.26 vs 0.48±0.69, both p<0.001). Conclusions There was high use of NSAIDs during the 2014 FIFA World Cup. Although the intake of NSAIDs per match (0.35±0.46 vs 0.31±0.48, p<0.01) in the 2014 FIFA World Cup decreased compared to the 2010 FIFA World Cup, the average use was still higher than in the 2006 FIFA World Cup, and the average number of all used medications per player remained the same level as 4 years prior, with all its implications for the player's health. More efforts need to be undertaken worldwide in order to reduce the administration of medications in sports, through continuous education for players, starting from a young age, as well as for doctors and paramedics.
Attributes of Aesthetic Quality Used by Textile Conservators in Evaluating Conservation Interventions on Museum Costumes

Aesthetic quality is central to textile conservators when evaluating a conservation method. However, the literature on textile conservation chiefly focuses on physical properties, and little is known about what factors determine aesthetic quality according to textile conservators. The latter was explored through two experiments. Experiment 1 explored the underlying attributes of aesthetic quality of textile conservation interventions. Experiment 2 explored the relationships between these attributes and how well they predicted aesthetic quality. Rank-order correlation analyses revealed two latent factors called Coherence and Completeness. Ordinal regression analysis revealed that Coherence was the most important predictor of aesthetic quality. This means that a successful conservation intervention is visually well-integrated with the textile item in terms of the material and method.
Search for poly(A) polymerase targets in E. coli reveals its implication in surveillance of Glu tRNA processing and degradation of stable RNAs

Polyadenylation is a universal post‐transcriptional modification involved in degradation and quality control of bacterial RNAs. In Escherichia coli, it is admitted that any accessible RNA 3′ end can be tagged by a poly(A) tail for decay. However, we do not have yet an overall view of the population of polyadenylated molecules. The sampling of polyadenylated RNAs presented here demonstrates that rRNA fragments and tRNA precursors originating from the internal spacer regions of the rrn operons, in particular, rrnB are abundant poly(A) polymerase targets. Focused analysis showed that Glu tRNA precursors originating from the rrnB and rrnG transcripts exhibit long 3′ trailers that are primarily removed by PNPase and to a lesser extent by RNase II and poly(A) polymerase. Moreover, 3′ trimming by exoribonucleases precedes 5′ end maturation by RNase P. Interestingly, characterization of RNA fragments that accumulate in a PNPase deficient strain showed that Glu tRNA precursors still harbouring the 5′ leader can be degraded by a 3′ to 5′ quality control pathway involving poly(A) polymerase. This demonstrates that the surveillance of tRNA maturation described for a defective tRNA also applies to a wild‐type tRNA.
Effect of luteinizing hormone-releasing hormone on the pituitary-gonadal axis in fetal and infant rhesus monkeys.

The response of the pituitary-gonadal axis to synthetic LHRH was investigated in fetal (gestational age, 150–159 days), infant (6 months old), and prepubertal (18 months old) rhesus monkeys. In the fetal studies, saline or 80 μg LHRH was adminstered in utero through a cannula placed in the femoral vein. Blood pressure was stable in both fetus and mother throughout each experiment. Immunoreactive serum LH was significantly elevated over control samples in fetal males (n = 3) and females (n = 8) and in infant (n = 6) and prepubertal females (n = 6) after LHRH administration; infant males (n = 4) showed no response. Prepubertal males were not studied. There was no change in LH levels in the maternal circulation after LHRH was given to the fetus, nor was there any change in LH levels in agematched fetuses given saline. Although LH levels were quantitatively different when measured by bioassay and immunoassay, both assays showed an increase in LH after LHRH adminstration. Serum titers of 17β-estradiol (E2) and.
Use of Multifidelity and Surrogate Models in the Design and Development of Physics‐Based Systems

Building a complex system in a time and cost effective manner, that performs well, meets diverse user needs, and has no inimical emergent behaviors is a challenge. The solution is to model before building. End‐to‐end high fidelity (HF) computational modeling and simulation (M&S) of a complex system, while attractive, is often too time consuming and expensive and may preclude the use of traditional systems engineering (SE) development tools. Missing are practicable approaches to reduce this computational time and cost by segmenting M&S performance and behaviors, keeping the model chain coherent, and only modeling what is necessary. An efficient framework is presented that couples mixed fidelity and surrogate models to reduce M&S computational time and cost for analysis of component‐level and system‐level performance of complex physics‐based problems. This framework is used in an example to modify a Nuclear Electromagnetic Pulse (NEMP) Bounded Wave Simulator (BWS). The framework is flexible and potentially extensible; it may provide systems engineers with a cost‐effective alternative to current approaches for modeling physics‐based engineering systems (e.g., radar, communications systems).