Stable X chromosome reactivation in female human induced pluripotent stem cells

In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to reactivation of the inactive X chromosome (Xi), we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR) and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas) or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas

Understanding the Operative Experience of the Practicing Pediatric Surgeon: Implications for Training and Maintaining Competency

Importance The number of practicing pediatric surgeons has increased rapidly in the past 4 decades, without a significant increase in the incidence of rare diseases specific to the field. Maintenance of competency in the index procedures for these rare diseases is essential to the future of the profession. Objective To describe the demographic characteristics and operative experiences of practicing pediatric surgeons using Pediatric Surgery Board recertification case log data. Design, Setting, and Participants We performed a retrospective review of 5 years of pediatric surgery certification renewal applications submitted to the Pediatric Surgery Board between 2009 and 2013. A surgeon’s location was defined by population as urban, large rural, small rural, or isolated. Case log data were examined to determine case volume by category and type of procedures. Surgeons were categorized according to recertification at 10, 20, or 30 years. Main Outcome and Measure Number of index cases during the preceding year. Results Of 308 recertifying pediatric surgeons, 249 (80.8%) were men, and 143 (46.4%) were 46 to 55 years of age. Most of the pediatric surgeons (304 of 308 [98.7%]) practiced in urban areas (ie, with a population >50 000 people). All recertifying applicants were clinically active. An appendectomy was the most commonly performed procedure (with a mean [SD] number of 49.3 [35.0] procedures per year), nonoperative trauma management came in second (with 20.0 [33.0] procedures per year), and inguinal hernia repair for children younger than 6 months of age came in third (with 14.7 [13.8] procedures per year). In 6 of 10 “rare” pediatric surgery cases, the mean number of procedures was less than 2. Of 308 surgeons, 193 (62.7%) had performed a neuroblastoma resection, 170 (55.2%) a kidney tumor resection, and 123 (39.9%) an operation to treat biliary atresia or choledochal cyst in the preceding year. Laparoscopy was more frequently performed in the 10-year recertification group for Nissen fundoplication, appendectomy, splenectomy, gastrostomy/jejunostomy, orchidopexy, and cholecystectomy (P < .05) but not lung resection (P = .70). It was more frequently used by surgeons recertifying in the 10-year group (used in 11 375 of 14 456 procedures [78.7%]) than by surgeons recertifying in the 20-year (used in 6214 of 8712 procedures [71.3%]) or 30-year group (used in 2022 of 3805 procedures [53.1%]). Conclusions and Relevance Practicing pediatric surgeons receive limited exposure to index cases after training. With regard to maintaining competency in an era in which health care outcomes have become increasingly important, these results are concerning

Neutral and Charged Polymers at Interfaces

Chain-like macromolecules (polymers) show characteristic adsorption properties due to their flexibility and internal degrees of freedom, when attracted to surfaces and interfaces. In this review we discuss concepts and features that are relevant to the adsorption of neutral and charged polymers at equilibrium, including the type of polymer/surface interaction, the solvent quality, the characteristics of the surface, and the polymer structure. We pay special attention to the case of charged polymers (polyelectrolytes) that have a special importance due to their water solubility. We present a summary of recent progress in this rapidly evolving field. Because many experimental studies are performed with rather stiff biopolymers, we discuss in detail the case of semi-flexible polymers in addition to flexible ones. We first review the behavior of neutral and charged chains in solution. Then, the adsorption of a single polymer chain is considered. Next, the adsorption and depletion processes in the many-chain case are reviewed. Profiles, changes in the surface tension and polymer surface excess are presented. Mean-field and corrections due to fluctuations and lateral correlations are discussed. The force of interaction between two adsorbed layers, which is important in understanding colloidal stability, is characterized. The behavior of grafted polymers is also reviewed, both for neutral and charged polymer brushes.Comment: a review: 130 pages, 30 ps figures; final form, added reference

Species composition, larval habitats, seasonal occurrence and distribution of potential malaria vectors and associated species of Anopheles (Diptera: Culicidae) from the Republic of Korea

<p>Abstract</p> <p>Background</p> <p>Larval mosquito habitats of potential malaria vectors and related species of <it>Anopheles </it>from three provinces (Gyeonggi, Gyeongsangbuk, Chungcheongbuk Provinces) of the Republic of Korea were surveyed in 2007. This study aimed to determine the species composition, seasonal occurrence and distributions of <it>Anopheles </it>mosquitoes. Satellite derived normalized difference vegetation index data (NDVI) was also used to study the seasonal abundance patterns of <it>Anopheles </it>mosquitoes.</p> <p>Methods</p> <p>Mosquito larvae from various habitats were collected using a standard larval dipper or a white plastic larval tray, placed in plastic bags, and were preserved in 100% ethyl alcohol for species identification by PCR and DNA sequencing. The habitats in the monthly larval surveys included artificial containers, ground depressions, irrigation ditches, drainage ditches, ground pools, ponds, rice paddies, stream margins, inlets and pools, swamps, and uncultivated fields. All field-collected specimens were identified to species, and relationships among habitats and locations based on species composition were determined using cluster statistical analysis.</p> <p>Results</p> <p>In about 10,000 specimens collected, eight species of <it>Anopheles </it>belonging to three groups were identified: Hyrcanus Group - <it>Anopheles sinensis</it>, <it>Anopheles kleini</it>, <it>Anopheles belenrae</it>, <it>Anopheles pullus</it>, <it>Anopheles lesteri</it>, <it>Anopheles sineroides</it>; Barbirostris Group - <it>Anopheles koreicus</it>; and Lindesayi Group - <it>Anopheles lindesayi japonicus</it>. Only <it>An. sinensis </it>was collected from all habitats groups, while <it>An. kleini, An. pullus </it>and <it>An. sineroides </it>were sampled from all, except artificial containers. The highest number of <it>Anopheles </it>larvae was found in the rice paddies (34.8%), followed by irrigation ditches (23.4%), ponds (17.0%), and stream margins, inlets and pools (12.0%). <it>Anopheles sinensis </it>was the dominant species, followed by <it>An. kleini, An. pullus </it>and <it>An. sineroides</it>. The monthly abundance data of the <it>Anopheles </it>species from three locations (Munsan, Jinbo and Hayang) were compared against NDVI and NDVI anomalies.</p> <p>Conclusion</p> <p>The species composition of <it>Anopheles </it>larvae varied in different habitats at various locations. <it>Anopheles </it>populations fluctuated with the seasonal dynamics of vegetation for 2007. Multi-year data of mosquito collections are required to provide a better characterization of the abundance of these insects from year to year, which can potentially provide predictive capability of their population density based on remotely sensed ecological measurements.</p

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro

BACKGROUND: The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. METHODS: Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. RESULTS: Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. CONCLUSIONS: THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Distribution of the k-th smallest Dirac operator eigenvalue

Based on the exact relationship to Random Matrix Theory, we derive the probability distribution of the k-th smallest Dirac operator eigenvalue in the microscopic finite-volume scaling regime of QCD and related gauge theories.Comment: REVTeX 3.1, 6 pages, 1 figure. Corrected factors in eqs. (16a) and (16c) and very minor typos (v2

Emotional design and human-robot interaction

Recent years have shown an increase in the importance of emotions applied to the Design field - Emotional Design. In this sense, the emotional design aims to elicit (e.g., pleasure) or prevent (e.g., displeasure) determined emotions, during human product interaction. That is, the emotional design regulates the emotional interaction between the individual and the product (e.g., robot). Robot design has been a growing area whereby robots are interacting directly with humans in which emotions are essential in the interaction. Therefore, this paper aims, through a non-systematic literature review, to explore the application of emotional design, particularly on Human-Robot Interaction. Robot design features (e.g., appearance, expressing emotions and spatial distance) that affect emotional design are introduced. The chapter ends with a discussion and a conclusion.info:eu-repo/semantics/acceptedVersio