Challenges in identifying cancer genes by analysis of exome sequencing data.

Massively parallel sequencing has permitted an unprecedented examination of the cancer exome, leading to predictions that all genes important to cancer will soon be identified by genetic analysis of tumours. To examine this potential, here we evaluate the ability of state-of-the-art sequence analysis methods to specifically recover known cancer genes. While some cancer genes are identified by analysis of recurrence, spatial clustering or predicted impact of somatic mutations, many remain undetected due to lack of power to discriminate driver mutations from the background mutational load (13-60% recall of cancer genes impacted by somatic single-nucleotide variants, depending on the method). Cancer genes not detected by mutation recurrence also tend to be missed by all types of exome analysis. Nonetheless, these genes are implicated by other experiments such as functional genetic screens and expression profiling. These challenges are only partially addressed by increasing sample size and will likely hold even as greater numbers of tumours are analysed

Internet Censorship Circumvention Technology Use in Human Rights Organizations: An Exploratory Analysis

Using an organizational informatics approach, this study explores the implications of human rights organizations’ use of censorship circumvention technologies. Through qualitative analyses of data collected through in-depth interviews, the research examines the factors influencing the use of circumvention technologies and the organizational effects of their use. The outcomes include a revised model of censorship circumvention technology use as well as a new model situating human rights organizations and their audiences in bidirectional information flows. The research provides recommendations for practice as well as insight for organizational informatics and information systems security research in the areas of protective technologies, awareness, detection, and physical security

Thermal Design of Astrobee Perching Arm

This paper presents the thermal design of actuators in the perching arm of Astrobee robot that will operate inside the International Space Station (ISS) starting in 2019. Since the crew's safety is of the utmost importance on the ISS, all materials used in the Astrobee robot should meet the touch temperature requirements according to the ISS safety standards to protect crew from skin burns by controlling the exposure temperature. The Astrobee perching arm consists of 2-DOF (Degrees-of-Freedom)- arm servo motors and 1-DOF gripper DC motor, which are capable of overheating in the stalled condition. Thermal properties of two types of actuators are verified by monitoring the touch temperature in worst-case operations with no thermal protection. Then, the proper thermal protection designs have been conducted and installed to guarantee the safety in all conditions

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment

Background: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. Results: We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. Conclusions: This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers

Sudden Collections Coordinators: When You Don’t Know What You Don’t Know

As new librarians enter the profession with varying levels of education and experience concerning library collection management, they may find themselves suddenly assigned the responsibility of coordinating collection activities within a subject area or for their entire library. From understanding terminology to working with acquisitions departments and from communicating with vendors to assessing resources, there is much to be learned in a short period of time. This paper will provide perspectives from five librarians at the George A. Smathers Libraries at the University of Florida (UF): the senior associate dean responsible for collections, the chair of the Acquisitions & Collections Services Department, an experienced collection coordinator, and two relatively new subject librarians who were recently asked to coordinate collection decisions for their respective areas (Humanities and Health Sciences). As one of the new collection coordinators came to subject librarianship from a specialized academic background and the other from a degree in library science, both newly promoted collection coordinators will present the unique difficulties faced in coming to collection coordination from their different educational backgrounds. This paper will address the large learning curve required when suddenly promoted to collection coordinator, including the steps of building a strong connection with acquisitions, developing vendor relations, and tracking collection development at the department level, while making suggestions for learning more along the way

Halothane hepatitis with renal failure treated with hemodialysis and exchange transfusion

A 38-year-old white female, hepatitis B antigen negative, developed fluminating hepatic failure associated with oliguria and severe azotemia after two halothane anesthesia and without exposure to other hepatotoxic drugs or blood transfusions. She was treated with multiple hemodialysis and exchange blood transfusion. The combined treatment corrected the uremic abnormalities and improved her level of consciousness. The liver and kidney function gradually improved, and she made a complete recovery, the first recorded with hepatic and renal failure under these post-anesthetic conditions. Further evaluation of this combined treatment used for this patient is warranted. © 1974 The Japan Surgical Society

A remarkably unsymmetric hexairon core embraced by two high-symmetry tripodal oligo-α-pyridylamido ligands

Oligo-α-pyridylamides offer an appealing route to polyiron complexes with short Fe-Fe separations and large room temperature magnetic moments. A derivative of tris(2‐aminoethyl)amine (H6tren) containing three oligo-α-pyridylamine branches and thirteen nitrogen donors (H6L) reacts with [Fe2(Mes)4] to yield an organic nanocage built up by two tripodal ligands with interdigitated branches (HMes = mesitylene). The nanocage has crystallographic D3 symmetry but hosts a remarkably unsymmetric hexairon-oxo core, with a central Fe5(μ5-O) square pyramid, two oxygen donors bridging basal sites, and an additional Fe center residing in one of the two tren-like pockets. Bond Valence Sum (BVS) analysis, Density Functional Theory (DFT) calculations, and electrochemical data were then used to establish the protonation state of oxygen atoms and the formal oxidation states of the metals. To this purpose, a specialized set of BVS parameters was devised for Fe2+-N3- bonds with nitrogen donors of oligo-α-pyridylamides. This allowed us to formulate the compound as [Fe6O2(OH)(H3L)L], with nominally four FeII and two FeIII ions. Mössbauer spectra indicate that the compound contains two unique FeII sites, identified as a pair of closely spaced hydroxo-bridged metal ions in the central Fe5(μ5-O) pyramid, and a substantially valence-delocalized FeII2FeIII2 unit. Broken-symmetry DFT calculations predict strong ferromagnetic coupling between the two iron(II) ions, leading to a local S = 4 state that persists to room temperature and explaining the large magnetic moment measured at 300 K. The compound behaves as a single-molecule magnet, with magnetization dynamics detectable in zero static field and dominated by an Orbach-like mechanism with Ueff/kB = 49(2) K and τ0 = 4(2)·10−10 s

Multifocal Adult Rhabdomyoma of the Head and Neck Manifestation in 7 Locations and Review of the Literature

Background. Adult rhabdomyoma is a rare benign tumour with the differentiation of striated muscle tissue, which mainly occurs in the head and neck region. Twenty-six cases of multifocal adult rhabdomyoma are documented in the literature. Method. We report a 55-year-old male with simultaneous diagnosis of 7 adult rhabdomyomas and review the literature of multifocal adult rhabdomyoma. Result. Review of the literature revealed 26 cases of multifocal adult rhabdomyoma, of which only 7 presented with more than 2 lesions. Mean age at diagnosis was 65 years with a male to female ratio of 5.5 : 1. Common localizations were the parapharyngeal space (36%), larynx (15%), submandibular (14%), paratracheal region (12%), tongue (11%), and floor of mouth (9%). Besides the known radiological features of adult rhabdomyoma, our case showed FDG-uptake in (18) F-FDG PET/CT. Conclusion. This is the first case of multifocal adult rhabdomyoma published, with as many as 7 simultaneous adult rhabdomyomas of the head and neck

A global transcriptional network connecting noncoding mutations to changes in tumor gene expression.

Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88% of tumors, suggesting widespread impact of noncoding mutations in cancer