Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimated prevalence of hereditary cancers and the need for surveillance in a Norwegian county, Telemark

Objective. The aim of the study was to estimate the prevalence of hereditary cancers and the need for surveillance in Telemark county, Norway. Material and methods. All persons attending the Norwegian Colorectal Cancer Prevention (NORCCAP) trial in Telemark were interviewed about cases of cancer in the family. Diagnoses were verified, pedigrees constructed and families classified according to preset criteria aiming at identifying hereditary cancer. Mutation analyses were performed in kindreds at risk for breast cancers when possible. Immunohistochemistry of tumors in assumed inherited colorectal cancer families was undertaken. Results. The screening examination was attended by 7224 persons among whom 2866 had cancer in the family. Of these, 2479 had no suspicion of any known inherited cancer syndrome. Family information questionnaires were mailed to 387 persons and returned by 191. Sixty-four of these 191 met the clinical criteria for familial cancer by family history after verification of diagnoses. Observed prevalences for being at risk for hereditary breast and breast–ovarian cancer (HBOC) or hereditary non-polyposis colorectal cancer (HNPCC) were 2.8‰ and 0.77‰, respectively. Conclusions. The number of colonoscopies and mammograms obtained per year serving those who needed them was limited and reduced by clinical genetic work-up from 2866 with a family history of cancer to 64 proven cases. Continued surveillance of an unnecessarily high number leads to unjustified cancer worry, is costly and uses up health-care facilities. Genetic work-up is a one-time job that reduces input numbers to surveillance programs, provides a starting-point for mutation testing and is economically cost beneficial if inherited cancers are prevented or cured by the health-care programs offered.
New and improved glucocorticoid receptor ligands

The therapeutic and prophylactic use of glucocorticoids is widespread due to their powerful anti-inflammatory, antiproliferative and immunomodulatory activity. However, long-term use of these drugs can result in severe dose-limiting side effects. One of the most critical and debilitating side effects is osteoporosis, which leads to increased risk of fractures. Glucocorticoids damage bone through several different mechanisms. The search for novel glucocorticoids that have reduced side effects in bone and other tissues is being driven by the identification of new mechanisms of action of the glucocorticoid receptor. This may facilitate the detection of new, safer therapies with efficacies equivalent to currently prescribed steroids.
The RNA Editing Factor SlORRM4 Is Required for Normal Fruit Ripening in Tomato1

SlORRM4 is necessary for timely fruit ripening, mitochondrial health, and RNA editing in tomato. RNA editing plays a key posttranscriptional role in gene expression. Existing studies on cytidine-to-uridine RNA editing in plants have focused on maize (Zea mays), rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana). However, the importance and regulation of RNA editing in several critical agronomic processes are not well understood, a notable example of which is fruit ripening. Here, we analyzed the expression profile of 33 RNA editing factors and identified 11 putative tomato (Solanum lycopersicum) fruit ripening-related factors. A rapid virus-induced gene silencing assay indicated that the organelle RNA recognition motif-containing protein SlORRM4 affected tomato fruit ripening. Knocking out SlORRM4 expression using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome editing strategy delayed tomato fruit ripening by lowering respiratory rate and ethylene production. Additionally, the expression of numerous genes associated with fruit ripening and mitochondrial functions changed significantly when SlORRM4 was knocked out. Moreover, the loss of SlORRM4 function significantly reduced RNA editing of many mitochondrial transcripts, leading to low-level expression of some core subunits that are critical for mitochondrial complex assembly (i.e. Nad3, Cytc1, and COX II). Taken together, these results indicate that SlORRM4 is involved in RNA editing of transcripts in ripening fruit that influence mitochondrial function and key aspects of fruit ripening.
Modeling and analyzing the influence of chunk size variation on bitrate adaptation in DASH

Recently, HTTP-based adaptive video streaming has been widely adopted in the Internet. Up to now, HTTP-based adaptive video streaming is standardized as Dynamic Adaptive Streaming over HTTP (DASH), where a client-side video player can dynamically pick the bitrate level according to the perceived network conditions. Actually, not only the available bandwidth is varying, but also the chunk sizes in the same bitrate level significantly fluctuate, which also influences the bitrate adaptation. However, existing bitrate adaptation algorithms do not accurately involve the chunk size variation, leading to performance losses. In this paper, we theoretically analyze the influence of chunk size variation on bitrate adaptation performance. Based on DASH system features, we build a general model describing the playback buffer evolution. Applying stochastic theories, we respectively analyze the influence of the chunk size variation on rebuffering probability and average bitrate level. Furthermore, based on theoretical insights, we provide several recommendations for algorithm designing and rate encoding, and also propose a simple bitrate adaptation algorithm. Extensive simulations verify our insights as well as the efficiency of the proposed recommendations and algorithm.
Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation

Autophagy is a conserved cellular process of macromolecule recycling that involves vesicle-mediated degradation of cytoplasmic components. Autophagy plays essential roles in normal cell homeostasis and development, the response to stresses such as nutrient starvation, and contributes to disease processes including cancer and neurodegeneration. Although many of the autophagy components identified from genetic screens in yeast are well conserved in higher organisms, the mechanisms by which this process is regulated in any species are just beginning to be elucidated. In a genetic screen in Drosophila melanogaster, we have identified a link between the focal adhesion protein paxillin and the Atg1 kinase, which has been previously implicated in autophagy. In mammalian cells, we find that paxillin is redistributed from focal adhesions during nutrient deprivation, and paxillin-deficient cells exhibit defects in autophagosome formation. Together, these findings reveal a novel evolutionarily conserved role for paxillin in autophagy.
Enhanced EMG signal processing for simultaneous and proportional myoelectric control

A new signal processing scheme is presented for extracting neural control information from the multi-channel surface electromyographic signal (sEMG). The extracted information can be used to proportionally control a multi-degree of freedom (DOF) prosthesis. Four time-domain (TD) features were extracted from the multi-channel sEMG during a series of anisotonic, isometric wrist contractions, which involved simultaneous activations of the three DOF of the wrist. The forces produced at the three wrist DOFs during these contractions were also collected using a customized force sensor. The extracted features and the recorded force signals, as input/target pairs, were then used to train a multilayer perceptron (MLP) neural network. A five-fold cross-validation training/testing method was applied. The resulting performance is a significant improvement over a previously proposed sEMG processing method for the proportional, multi-DOF myoelectric control task.
Alpha model based mixed pixel processing for view synthesis

The commercial success and acceptability of 3D technology will critically depend on the overall visual quality of the rendered images. Therefore, view synthesis techniques like Depth Image Based Rendering (DIBR) are crucial components of the 3D system chain. In this paper, we propose a fast α-model based approach that enables high quality DIBR. Given an image and depth map, a point based representation of the scene is obtained, where each point is associated with color, transparency and depth. A low complexity method estimates these attributes, making the system suitable for deployment in consumer electronics.
Microbial reporter gene assay as a diagnostic and early warning tool for the detection and characterization of toxic pollution in surface waters

Surface water samples constantly receive a vast mixture of micropollutants mainly originating from wastewater treatment plants (WWTPs). High‐throughput live cell arrays provide a promising method for the characterization of the effects of chemicals and the associated molecular mechanisms. In the present study, this test system was evaluated for the first time for the characterization of a set of typical surface water extracts receiving effluent from WWTPs. The extracts containing complex mixtures of micropollutants were analyzed for the expression of 90 stress responsive genes in the Escherichia coli reporter gene assay. The most affected pathways and the genes most sensitive to surface water samples suggested prominent stress‐responsive pathways for wastewater‐impacted surface water, such as oxidative stress, DNA damage, and drug resistance. Samples strongly affecting particular pathways were identified by statistical analysis of gene expression. Transcription data were correlated with contamination data from chemical screening and percentages of wastewater in the samples. Samples with particular effects and outstanding chemical composition were analyzed. For these samples, hypotheses on the alteration of the transcription of genes involved in drug resistance and DNA repair attributable to the presence of pharmaceuticals were drawn. Environ Toxicol Chem 2015;34:2523–2532. © 2015 SETAC
Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair

Significance BAP1 is a deubiquitinase of histone H2A involved in chromatin remodeling. Several studies identified BAP1 as major tumor suppressor inactivated in various cancers. Nonetheless, the manner in which BAP1 protects against cancer development remains enigmatic. We now show that BAP1 is recruited to double-strand DNA break sites and promotes error-free repair of these lesions. We also provide the first evidence that phosphorylation coordinates the function of BAP1 in promoting cellular recovery from DNA damage. Thus, our study represents a significant advance in the field of ubiquitin signaling in the context of cancer development. The cellular response to highly genotoxic DNA double-strand breaks (DSBs) involves the exquisite coordination of multiple signaling and repair factors. Here, we conducted a functional RNAi screen and identified BAP1 as a deubiquitinase required for efficient assembly of the homologous recombination (HR) factors BRCA1 and RAD51 at ionizing radiation (IR) -induced foci. BAP1 is a chromatin-associated protein frequently inactivated in cancers of various tissues. To further investigate the role of BAP1 in DSB repair, we used a gene targeting approach to knockout (KO) this deubiquitinase in chicken DT40 cells. We show that BAP1-deficient cells are (i) sensitive to IR and other agents that induce DSBs, (ii) defective in HR-mediated immunoglobulin gene conversion, and (iii) exhibit an increased frequency of chromosomal breaks after IR treatment. We also show that BAP1 is recruited to chromatin in the proximity of a single site-specific I-SceI–induced DSB. Finally, we identified six IR-induced phosphorylation sites in BAP1 and showed that mutation of these residues inhibits BAP1 recruitment to DSB sites. We also found that both BAP1 catalytic activity and its phosphorylation are critical for promoting DNA repair and cellular recovery from DNA damage. Our data reveal an important role for BAP1 in DSB repair by HR, thereby providing a possible molecular basis for its tumor suppressor function.
Golgi Fragmentation Occurs in the Cells with Prefibrillar α-Synuclein Aggregates and Precedes the Formation of Fibrillar Inclusion*

Amyloid-like fibrillar aggregates of intracellular proteins are common pathological features of human neurodegenerative diseases. However, the nature of pathogenic aggregates and the biological consequences of their formation remain elusive. Here, we describe (i) a model cellular system in which prefibrillar α-synuclein aggregates and fibrillar inclusions are naturally formed in the cytoplasm with distinctive kinetics and (ii) a tight correlation between the presence of prefibrillar aggregates and the Golgi fragmentation. Consistent with the structural abnormality of Golgi apparatus, trafficking and maturation of dopamine transporter through the biosynthetic pathway were impaired in the presence of α-synuclein aggregates. Reduction in cell viability was also observed in the prefibrillar aggregate-forming condition and before the inclusion formation. The fibrillar inclusions, on the other hand, showed no correlation with Golgi fragmentation and were preceded by these events. Furthermore, at the early stage of inclusion formation, active lysosomes and mitochondria were enriched in the juxtanuclear area and co-aggregate into a compact inclusion body, suggesting that the fibrillar inclusions might be the consequence of an attempt of the cell to remove abnormal protein aggregates and damaged organelles. These results support the hypothesis that prefibrillar α-synuclein aggregates are the pathogenic species and suggest that Golgi fragmentation and subsequent trafficking impairment are the specific consequence of α-synuclein aggregation.
Dynamic PET image reconstruction using a spatial-temporal edge-preserving prior

Dynamic positron emission tomography (PET) imaging provides important quantitative information of physiological and biochemical processes in humans and animals. However, due to short-time acquisitions to obtain a time sequence of images for parametric imaging, the signal-to-noise ratio of measurement data in each time frame is often very low, which leads the dynamic PET image reconstruction to be a challenging task. And some noticeable errors are inevitable transferred to the voxel-wise kinetic parameter imaging from the associative noisy TAC measurements. To tackle this problem, maximum a posteriori (MAP) statistical reconstruction methods are widely used by incorporating some prior information. Conventional priors focus on local neighborhoods in individual image frames and subsequently penalize inter-voxel intensity differences through different penalty functions such as the quadratic membrane smoothing prior and non-quadratic edge-preserving prior, failing to explore the temporal information of dynamic PET data. In this paper, we design a spatial-temporal edge-preserving (STEP) prior model under the framework of bilateral filter by considering both the spatial local neighborhoods and the temporal kinetic information. Experimental results via a computer simulation study demonstrate that the present dynamic PET reconstruction method with the STEP prior can achieve noticeable gains than the conventional Huber prior in term of signal-to-noise and bias-variance evaluations for the parametric images.
Atomic Structures and Electronic States of Divalent Bismuth in Bi-Doped Silica Optical Fiber

We report first-principles calculations of cluster SiO2 (24-atom) with and without divalent bismuth (Bi2+). Heyd–Scuseria–Ernzerhof functional is introduced. The influences of members of “Si-O-Si” rings are considered to study atomic structures, electronic structures, and optical properties of Bi-doped optical fiber. Our results reveal that Bi-doped in 3-membered rings are main contributions to the characteristic absorption bands (around 500 nm), which will lead a red emission in Bi-doped optical fiber. Our methods will be effective to confirm bismuth-active centers for different valence states of Bi atom.
Comparison of rates of fecal colonization with extended‐spectrum beta‐lactamase‐producing enterobacteria among patients in different wards, outpatients and medical students

Because asymptomatic carriage of extended‐spectrum beta‐lactamase (ESBL) producers is a risk factor for infection, data on colonization dynamics are important when planning infection control. This study investigated fecal colonization with ESBL producers among inpatients, outpatients and medical students and compares the characteristics of ESBL producers among these groups. Carriage rates were investigated in 5581 fecal samples; 4343 from inpatients (330, 1397, 619 and 1864 from adult ICUs [intensive care units], adult non‐ICUs, pediatric ICUs and pediatric non‐ICUs, respectively), 814 from outpatients and 424 from screening of medical students. ESBL producers were characterized by co‐resistance, integrons carried, and aminoglycoside resistance and ESBL genes. Dynamic regression models were built to identify relationships between combinations of time series of monthly antibiotic consumption, prevalence of carriers and infected subjects. Inpatients, ICU patients and adults showed higher prevalence than outpatients, non‐ICU patients or children (7.4%, 9.3% and 12.0% vs. 3.1%, 6.1% and 4.1%, respectively). Klebsiella pneumoniae was more frequent in ICU patients; dominance of CTX‐M‐15 producers was more marked in adult than in pediatric inpatients. ESBL carriage was shown to be a consequence of infection in adults in the time‐series analysis; antibiotic consumption had little effect. The epidemiology of colonization with ESBL producers differed between pediatric ICU, adult ICU and adult non‐ICU patients. In adults, carriage of ESBL producers seems to be the consequence of infection, especially in ICU patients; the main source of colonization is nosocomial acquisition. In contrast, children are less likely to acquire colonizer strains in hospitals; importation of ESBL producers by colonized children seems to be significant.
Identification of Three Genes Encoding for the Late Acyltransferases of Lipid A in Cronobacter sakazakii

Lipid A, the hydrophobic anchor of lipopolysaccharide, is an essential component in the outer membrane of most Gram-negative bacteria. Food-borne pathogen Cronobacter sakazakii synthesizes two lipid A species, differing by the length of the secondary acyl chain. In this work, we identified three genes ESA02293, ESA02951 and ESA01386 encoding for the late acyltransferases of lipid A biosynthesis pathway in C. sakazakii. Based on the sequence alignment, proteins YP_001438378. 1 encoded by ESA02293, YP_001439016. 1 encoded by ESA02951, and YP_001437482. 1 encoded by ESA01386 are homologous to E. coli LpxL, LpxP and LpxM, respectively. Functions of the three acyltransferases were confirmed by overexpressing the genes in E. coli, isolating lipid As and analyzing their structures using an ESI/MS. C. sakazakii LpxL and LpxM transfer a C14:0 secondary acyl chain to the 2′- and 3′-position of lipid A, respectively. C. sakazakii LpxP can transfer either a C16:1 or a C14:0 secondary acyl chains to the 2′-position of lipid A.
Identification of Isolates of Streptococcus canisInfecting Humans

ABSTRACT During a survey of Group G and C streptococcal infections of humans two epidemiologically unrelated Group G streptococcal isolates were identified, one from a case of bacteremia and one from a wound infection. These isolates were atypical among this sample in that theemm gene could not be amplified from them by PCR. Biochemical characterization identified the isolates asStreptococcus canis, an organism normally associated with animal hosts. The biochemical identification was confirmed by sequencing of the 16S rRNA gene from both isolates and comparison with sequences of the S. canis type strain and other related streptococci of animals and humans. Comparative sequencing of fragments of two other housekeeping genes, sodA andmutS, confirmed that the isolates are most closely related to S. canis. The identification of two isolates of S. canis from a relatively small sample set suggests that the practice of identifying streptococci only by the Lancefield serological group may result in underestimation of the presence ofS. canis in the human population.
Peace and Power: New Directions for Building Community

In the years since the publication of the first edition of Peace and Power: New Directions for Building Community, the author has refined the processes outlined in the book through her experiences in classrooms, committees, and workshops, building meaningful relationships through a nurturing and empowering leadership method. The Eighth Edition of Peace and Power benefits from these years of positive and constructive leadership experiences. This Edition of Peace and Power focuses on clarity, highlighting key elements of group interactions that promote greater group integrity and cooperation. Readers of Peace and Power will benefit from a handbook that inspires ways of incorporating value into work, home, and community. For eight editions, nurse leaders have relied on this book to provide a hands-on guide for developing cooperative group processes and for overcoming the habits of exclusionary group interactions. This book remains a valuable resources for community groups, classes, committees, and others seeking to create change toward a more equitable model and more satisfying (peaceful) group interactions.
Role of Actin-binding Protein in Insertion of Adhesion Receptors into the Membrane*

The goal of this study was to determine whether actin-binding protein (ABP) regulates membrane composition. ABP-deficient and ABP-containing cells were transfected with the cDNAs coding for glycoprotein (GP) Ib-IX, a platelet receptor that interacts with ABP. Most of the GP Ib-IX remained inside the ABP-deficient cells. When ABP was present, functional GP Ib-IX was inserted into the membrane. GP Ib-IX lacking the domain that interacts with ABP also showed increased membrane insertion in ABP-expressing cells. Furthermore, a fragment of ABP that lacks the dimerization and GP Ib-IX-binding sites restored the spreading of the cells and increased the amount of GP Ib-IX in the membrane. Finally, expression of ABP also increased endogenous β1 integrin in the membrane. These results indicate that 1) ABP maintains the properties of the cell such that adhesion receptors can be efficiently expressed in the membrane; 2) increased receptor expression is accompanied by increased ability of the cell to spread; and 3) ABP exerts its effect by a mechanism that does not appear to involve direct cross-linking of actin filaments or direct interaction with receptors.