Miracle-dz/UniFAR-FTUs huggingface dataset:
Tyrosinase Maturation and Oligomerization in the Endoplasmic Reticulum Require a Melanocyte-specific Factor*

Tyrosinase is a glycoprotein responsible for the synthesis of melanin in melanocytes. A large number of mutations have been identified in tyrosinase, with many leading to its misfolding, endoplasmic reticulum (ER) retention, and degradation. Here we describe the folding and maturation of human tyrosinase (TYR) using an in vitro translation system coupled with ER-derived microsomes or with semipermeabilized cells, as an intact ER source. TYR remained misfolded as determined by its sensitivity to trypsin digestion and its persistent interaction with the ER resident lectin chaperones calnexin and calreticulin when produced in ER-derived microsomes or nonmelanocytic semipermeabilized cells. However, when TYR was translocated into semipermeabilized melanocytes, chaperone interactions were transient, maturation progressed to a trypsin-resistant state, and a TYR homodimer was formed. The use of semipermeabilized mouse melanocytes defective for tyrosinase or other melanocyte-specific proteins as the ER source indicated that proper TYR maturation and oligomerization were greatly aided by the presence of wild type tyrosinase and tyrosinase-related protein 1. These findings suggested that oligomerization is a step in proper TYR maturation within the ER that requires melanocyte-specific factors.
Foreign Policy and Discourse Analysis: France, Britain and Europe

Henrik Larsen presents discourse analysis as an alternative approach to foreign policy analysis. Through an extensive empirical study of British and French policies towards Europe in the 1980s, he demonstrates the importance of political discourse in shaping foreign policy. The author discusses key theoretical problems within traditional belief system approaches and proposes an alternative one: political discourse analysis. The theory is illustrated through detailed analyses of British and French discourses on Europe, nation/state security and the nature of international relations.
On the TCP Flow Inter-arrival Times Dsitribution

IP packets are known to have long range dependence and show self-similar properties. However, TCP flows-a set of related IP packets that form a TCP connection-which are considered to be generated by a large population of users and consequently mutually independent, seem to be best modeled by either Poisson processes with exponential inter-arrival times or some distributions with heavy tails such as Weibull distribution. In this paper, we show that despite the number of active nodes in a network, the inter-arrival times of TCP flows in the "normal traffic" conform to the Weibull distribution and any irregularity in the traffic causes deviations in the distribution of the inter-arrival times and so can be detected. This leads to a straightforward method for anomaly detection by which we are able to identify the anomalous part(s) of the traffic. We first apply the median-rank method to estimate the Weibull distribution parameters of the traffic and then check the conformity of the data against a Weibull distribution with the estimated parameters and determine whether the traffic is normal or not based on the chi-square test.
Increase of melanocytic nevus counts in children during 5 years of follow-up and analysis of associated factors.

OBJECTIVES To investigate nevus development in childhood and to examine causative related factors such as pigment phenotype and the role of sun exposure in the development of melanocytic nevi. DESIGN AND PARTICIPANTS Nevus counts were performed in kindergarteners (n = 866) before the age of 7 years and again 5 years later (n = 377). Eligible for analysis were 357 children who were examined twice. Possible related factors were searched for by standardized interviews with parents. RESULTS The mean number of nevi measuring 1 mm or more was 9 in the first examination and the number measuring 2 mm or more, 4. Five years later, the mean number of nevi measuring 1 mm or more was 40 and the number measuring 2 mm or more was 16. Children with poor sun tolerance had statistically significant more nevi (relative risk, 3.7;95% confidence interval, 1.9-7.2). The presence of freckles was a strong predictor for a high increase of melanocytic nevi (relative risk, 2.1; 95% confidence interval, 1.3-3.3). The number of days per year with intensive solar exposure was an independent prognostic factor. The relative risk for the development of melanocytic nevi was increased by a factor of 1.6 in children who had more than 21 days of intensive sun exposure per year (95% confidence interval, 1.0-2.5). CONCLUSION The development of melanocytic nevi in childhood is strongly related to characteristics of pigmentation associated with poor sun tolerance. In addition, we found evidence for the influence of UV radiation on the number of acquired melanocytic nevi in childhood.
Power factor compensation with lossless linear filters is equivalent to (weighted) power equalization and a new cyclo-dissipativity characterization

Recently, it has been established that the problem of power factor compensation for nonlinear loads with non-sinusoidal source voltage can be recast in terms of the property of cyclo-dissipativity. Using this framework the classical capacitor and inductor compensators can be interpreted in terms of energy equalization. Unfortunately, the supply rate is a function of the load, which is usually unknown, styming the applicability of this result for compensator synthesis. The purpose of this brief note is to extend this approach in three directions. First, power factor compensation is shown to be equivalent to a new cyclo-dissipativity condition, whose supply rate is now function of the compensator. Second, we consider general lossless linear filters as compensators and show that the power factor is improved if and only if a certain equalization condition between the weighted powers of inductors and capacitors of the load is ensured. Finally, we exhibit the gap between the ideal compensator, e.g., the one that achieves unitary power factor, and the aforementioned equalization condition. This result naturally leads to the formulation of a problem of optimization of the compensator topology and its parameters.
Gene Expression in Hair Follicle Dermal Papilla Cells after Treatment with Stanozolol

Doping with anabolic agents is a topic in sports where strength is crucial, e.g. sprinting, weight lifting and many more. Testosterone and its functional analogs are the drugs of choice taken as pills, creams, tape or injections to increase muscle mass and body performance, and to reduce body fat. Stanozolol (17β-hydroxy-17α-methyl-5α-androst-2-eno[3,2c]pyrazol) is a testosterone analogue with the same anabolic effect like testosterone but its ring structure makes it possible to take it orally. Therefore, stanozolol is one of the most frequently used anabolic steroids. Common verification methods for anabolic drugs exist, identifying the chemicals in tissues, like hair or blood samples. The idea of this feasibility study was to search for specific gene expression regulations induced by stanozolol to identify the possible influence of the synthetically hormone on different metabolic pathways. Finding biomarkers for anabolic drugs could be supportive of the existing methods and an additional proof for illegal drug abuse. In two separate cell cultures, human HFDPC (hair follicle dermal papilla cells) from a female and a male donor were treated with stanozolol. In the female cell culture treatment concentrations of 0 nM (control), 1 nM, 10 nM and 100 nM were chosen. Cells were taken 0 h, 6 h, 24 h and 48 h after stimulation and totalRNA was extracted. Learning from the results of the pilot experiment, the male cell culture was treated in 10 nM and 100 nM concentrations and taken after 0 h, 6 h, 24 h and 72 h. Using quantitative real-time RT-PCR expression of characteristics of different target genes were analysed. Totally 13 genes were selected according to their functionality by screening the actual literature and composed to functional groups: factors of apoptosis regulation were Fas Ligand (FasL), its receptor (FasR), Caspase 8 and Bcl-2. Androgen receptor (AR) and both estrogen receptors (ERα, ERβ) were summarized in the steroid receptor group. The growth factor group included the insulin like growth factor receptor (IGF1R) and growth hormone receptor (GHR). Fibroblast growth factor 2 (FGF2) and keratinocyte growth factor (FGF7) were summarized in the hair cycle factor group. 5α-Steroidreductases (SRD5A1, SRD5A2) represented the enzyme group. Three reference genes were taken for relative quantification: ubiquitin (UBQ), glycerinaldehyde-3-phsophate-dehydrogenase (GAPDH), and β-actin (ACTB). In cell culture 1 AR, FasR, FGF2 showed significant regulations within one treatment time, significant gene expressions over time were analysed for Caspase 8. In cell culture 2 AR, FasR and SRD5A2 were significantly regulated within one treatment time. In this feasibility study first biomarker for a screening pattern of anabolic agents could be identified providing the rationality to investigate modified, metabolic pathways in the whole hair follicle.
Multi-RELIEF: a method to recognize specificity determining residues from multiple sequence alignments using a Machine-Learning approach for feature weighting

MOTIVATION Identification of residues that account for protein function specificity is crucial, not only for understanding the nature of functional specificity, but also for protein engineering experiments aimed at switching the specificity of an enzyme, regulator or transporter. Available algorithms generally use multiple sequence alignments to identify residue positions conserved within subfamilies but divergent in between. However, many biological examples show a much subtler picture than simple intra-group conservation versus inter-group divergence. RESULTS We present multi-RELIEF, a novel approach for identifying specificity residues that is based on RELIEF, a state-of-the-art Machine-Learning technique for feature weighting. It estimates the expected 'local' functional specificity of residues from an alignment divided in multiple classes. Optionally, 3D structure information is exploited by increasing the weight of residues that have high-weight neighbors. Using ROC curves over a large body of experimental reference data, we show that (a) multi-RELIEF identifies specificity residues for the seven test sets used, (b) incorporating structural information improves prediction for specificity of interaction with small molecules and (c) comparison of multi-RELIEF with four other state-of-the-art algorithms indicates its robustness and best overall performance. AVAILABILITY A web-server implementation of multi-RELIEF is available at www.ibi. vu.nl/programs/multirelief. Matlab source code of the algorithm and data sets are available on request for academic use.
Place Attachment: An Investigation Of Environments And Outcomes In A Service Context

iii ACKNOWLEDGEMENTS I would first and foremost like to thank my advisor Dr. Julie Baker. She has provided support and expertise throughout this process. Beyond being a wonderful mentor she has been a true friend. I thank her for the long hours spent helping me and providing me with emotional support. I have completed this work because of her dedication. I would especially like to thank my gracious husband, Matt. His compassion and foundation have meant the world to me. I have never met someone so giving and generous in all my life. He is the reason I have fulfilled my dreams. I only hope to someday return the favor. Several other individuals provided support and input into this dissertation. Dr. Susan Kleiser, who unselfishly gave her time to help me with the research methods and results sections. She has been a great friend and support throughout this process. I would have not been able to complete this research without her help. I would also like to thank Dr. Charles Lamb who imparted his wisdom and knowledge of the academic profession along with " pushing " me to complete my work in a timely fashion. His encouragement helped me when I thought things were not possible. He is a great friend and mentor. My family has been a pillar of strength and support for me. They have been an inspiration throughout my life. My mother has dedicated many hours to helping make iv my presentations clean and professional. She has been a constant source of support for me my entire life. I thank my Dad and Kathy who reminded me of the most important thing about a dissertation " finishing it ". I am grateful to my sisters Ashley and Rachel who never quite knew what I was doing but still wanted to help out and give encouragement. I express gratitude to my grandmothers; Nadine who always wanted to know how I was doing and kept track of my accomplishments and Maxine, who was not able to see this work complete, but who is always in my thoughts. Finally, I want to thank my friends. Pam and Hieu thank you for the long hours spent studying. We have helped each other in so many ways. I thank Stacy for her support and perseverance. I would also like to thank Jeanette Hood for always being there for me and helping me …
Synergistic Actions of Hematopoietic and Mesenchymal Stem/Progenitor Cells in Vascularizing Bioengineered Tissues

Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs) and mesenchymal stem/progenitor cells (MSCs) were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP) scaffolds, followed by infusion of gel-suspended CD34+ hematopoietic cells. Co-transplantation of CD34+ HSCs and CD34− MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromized mice yielded vascularized tissue. The average vascular number of co-transplanted CD34+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34+ cells. Based on additional in vitro results of endothelial differentiation of CD34+ cells by vascular endothelial growth factor (VEGF), we adsorbed VEGF with co-transplanted CD34+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone, adipose, muscle and dermal grafts, and may have implications in the regeneration of internal organs.
Relationships among fitness, body composition, and physical activity.

PURPOSE This study was designed to examine the associations of physical activity and body composition with cardiorespiratory fitness in eighth grade girls. METHODS A random sample of 1440 eighth grade girls at 36 schools participated in this cross-sectional investigation, which represented an ethnically and geographically diverse group. Cardiorespiratory fitness was assessed using a modified physical work capacity test on a cycle ergometer that predicted workload at a heart rate of 170 beats.min. Physical activity was assessed over 6 d in each girl using an accelerometer and body composition was estimated from body mass index and triceps skinfolds using a previously validated equation. Pearson correlations and multiple regression analyses were used to determine the relationships among fitness, physical activity, and body composition. RESULTS Significant linear relationships among cardiorespiratory fitness, body composition, and physical activity were found. The combination of fat and fat-free mass along with racial group and a race by fat-free-mass interaction accounted for 18% (R) of the variation in physical fitness. Adding moderate-to-vigorous physical activity to the regression model increased the R to 22%. Black girls had somewhat lower fitness levels (P < 0.05) especially at higher levels of fat and fat-free mass than other racial/ethnic groups. CONCLUSIONS Physical activity, fat-free mass, and the interaction between fat-free mass and racial group are significantly associated with cardiorespiratory fitness in adolescent girls.
Effects of Age on the Detection and Management of Breast Cancer

Currently, breast cancer affects approximately 12% of women worldwide. While the incidence of breast cancer rises with age, a younger age at diagnosis is linked to increased mortality. We discuss age related factors affecting breast cancer diagnosis, management and treatment, exploring key concepts and identifying critical areas requiring further research. We examine age as a factor in breast cancer diagnosis and treatment relating it to factors such as genetic status, breast cancer subtype, hormone factors and nodal status. We examine the effects of age as seen through the adoption of population wide breast cancer screening programs. Assessing the incidence rates of each breast cancer subtype, in the context of age, we examine the observed correlations. We explore how age affects patient’s prognosis, exploring the effects of age on stage and subtype incidence. Finally we discuss the future of breast cancer diagnosis and treatment, examining the potential of emerging tests and technologies (such as microRNA) and how novel research findings are being translated into clinically relevant practices.
If we offer it, will children buy it? Sales of healthy foods mirrored their availability in a community sport, commercial setting in Alberta, Canada.

BACKGROUND Community sports settings are often sources of unhealthy foods for children. Many managers in these settings are reluctant to increase availability of healthy food options because they perceive that healthy foods are not profitable. This study assessed the independent contribution of increased availability of healthy foods to their sales in a community sport, commercial context. Change in revenues per patron was also examined. METHODS The availability of healthy items was increased from 9.1% at baseline (35 days) to 25.0% during the intervention period (40 days), returning to 9.1% postintervention (6 days). Purchases of all patrons who bought foods/beverages (n=17,262 items sold) from two concessions at an outdoor community pool were assessed from baseline to postintervention. Chi-square analyses assessed differences in the proportion of healthy and unhealthy items sold, as well as in the proportion of total revenues per patron across periods. A trained observer also recorded qualitative observations pertaining to a subset of patrons' (n=221) dietary behaviors and activities. RESULTS Healthy items represented 7.7%, 22.7%, and 9.8% of sales during the preintervention, intervention, and postintervention periods, respectively (p<0.01). Sales of healthy beverages exceeded sales of all other product types. The proportion of total revenues per patron did not differ by period. CONCLUSIONS Food availability was an important environmental determinant of food purchasing behaviors in this community commercial context, given that sales of healthy foods closely mirrored their availability. Increased availability of healthy foods in community and commercial settings is important because concurrent changes within multiple environments will be required to improve children's dietary behaviors.
Analysis of Chimpanzee History Based on Genome Sequence Alignments

Population geneticists often study small numbers of carefully chosen loci, but it has become possible to obtain orders of magnitude for more data from overlaps of genome sequences. Here, we generate tens of millions of base pairs of multiple sequence alignments from combinations of three western chimpanzees, three central chimpanzees, an eastern chimpanzee, a bonobo, a human, an orangutan, and a macaque. Analysis provides a more precise understanding of demographic history than was previously available. We show that bonobos and common chimpanzees were separated ∼1,290,000 years ago, western and other common chimpanzees ∼510,000 years ago, and eastern and central chimpanzees at least 50,000 years ago. We infer that the central chimpanzee population size increased by at least a factor of 4 since its separation from western chimpanzees, while the western chimpanzee effective population size decreased. Surprisingly, in about one percent of the genome, the genetic relationships between humans, chimpanzees, and bonobos appear to be different from the species relationships. We used PCR-based resequencing to confirm 11 regions where chimpanzees and bonobos are not most closely related. Study of such loci should provide information about the period of time 5–7 million years ago when the ancestors of humans separated from those of the chimpanzees.
Treatment of hyperkinetic emotionally disturbed children with prolonged administration of chlorpromazine.

Twenty-five hyperkinetic, emotionally disturbed children were treated with chlorpromazine for periods lasting from 4 to 16 months. They also served as their own controls by receiving placebo medication for 4 to 6 weeks during some phase of treatment. Response was determined from the following observations: (1) Clinical changes noted by the clinic staff which included the social worker and psychologist as well as the therapist; (2) data from the home environment; (3) reports from the school counselors; (4) changes in the battery of psychological tests done before and after treatment. Improvement in varying degrees was noted in 21 cases—84%, and was marked in 70%. Diminution in hyperactivity was the outstanding phenomenon. Combativeness was reduced considerably. There was definite improvement in willingness to learn. The psychological testing suggested that the learning process was facilitated. Trends toward increased emotional control were evidenced although the basic personality seemed unchanged. The proc.