Canine Dominance Aggression

Each year, millions of dogs are taken to humane shelters across the United States. Of these dogs, it has been estimated that 15-20 million of them are euthanized. The majority of these animals are taken to shelters for some sort of behavioral problem, and by far, the most common behavioral problem found in dogs is aggressiveness. Canine aggression can be defined as an inappropriate threat, challenge, or attack by a dog against another dog, animal, or person in a given situation. It is important to realize that not all canine aggression is inappropriate-remember, one of the reasons dogs were originally domesticated was for protection. When a dog attacks visitors or family members, however, it is an inappropriate response. For all aggressive dogs, it is very important to determine the appropriateness of the behavior. Was the dog threatened, or was the aggressiveness really unprovoked

Competition between Carrier Injection and Structural Distortions in Electron‐Doped Perovskite Nickelate Thin Films

The discovery of superconductivity in doped infinite‐layer nickelate thin films has brought increased attention to the behavior of the doped perovskite phase. Despite this interest, the majority of existing studies pertain to hole‐doped perovskite rare‐earth nickelate thin films, while most electron‐doping studies have been performed on bulk materials so far. To tackle this imbalance, a detailed study that addresses doping of NdNiO$_{3}$ thin films using A‐site substitution is presented, using Pb as a dopant and taking advantage of its valence‐skipping nature. Through a combination of complementary techniques including X‐ray diffraction, transport measurements, X‐ray absorption spectroscopy, electron energy‐loss spectroscopy and scanning transmission electron microscopy, the valence of Pb in the Nd$_{1−x}$Pb$_{x}$NiO$_{3}$ structure is confirmed to be 4+, and the behavior of the doped thin films is found to be controlled by a competition between carrier injection and structural distortions, which respectively reduce and increase the metal‐to‐insulator transition temperature. This work provides a systematic study of electron doping in NdNiO$_{3}$, demonstrating that A‐site substitution with Pb is an appropriate method for such doping in perovskite rare‐earth nickelate systems

Competition between Carrier Injection and Structural Distortions in Electron-Doped Perovskite Nickelate Thin Films

The discovery of superconductivity in doped infinite-layer nickelate thin films has brought increased attention to the behavior of the doped perovskite phase. Despite this interest, the majority of existing studies pertain to hole-doped perovskite rare-earth nickelate thin films, while most electron-doping studies have been performed on bulk materials so far. To tackle this imbalance, a detailed study that addresses doping of NdNiO thin films using A-site substitution is presented, using Pb as a dopant and taking advantage of its valence-skipping nature. Through a combination of complementary techniques including X-ray diffraction, transport measurements, X-ray absorption spectroscopy, electron energy-loss spectroscopy and scanning transmission electron microscopy, the valence of Pb in the NdPbNiO structure is confirmed to be 4+, and the behavior of the doped thin films is found to be controlled by a competition between carrier injection and structural distortions, which respectively reduce and increase the metal-to-insulator transition temperature. This work provides a systematic study of electron doping in NdNiO, demonstrating that A-site substitution with Pb is an appropriate method for such doping in perovskite rare-earth nickelate systems

First events from the CNGS neutrino beam detected in the OPERA experiment

The OPERA neutrino detector at the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in appearance mode, through the study of nu_mu to nu_tau oscillations. The apparatus consists of a lead/emulsion-film target complemented by electronic detectors. It is placed in the high-energy, long-baseline CERN to LNGS beam (CNGS) 730 km away from the neutrino source. In August 2006 a first run with CNGS neutrinos was successfully conducted. A first sample of neutrino events was collected, statistically consistent with the integrated beam intensity. After a brief description of the beam and of the various sub-detectors, we report on the achievement of this milestone, presenting the first data and some analysis results.Comment: Submitted to the New Journal of Physic

Asteroids' physical models from combined dense and sparse photometry and scaling of the YORP effect by the observed obliquity distribution

The larger number of models of asteroid shapes and their rotational states derived by the lightcurve inversion give us better insight into both the nature of individual objects and the whole asteroid population. With a larger statistical sample we can study the physical properties of asteroid populations, such as main-belt asteroids or individual asteroid families, in more detail. Shape models can also be used in combination with other types of observational data (IR, adaptive optics images, stellar occultations), e.g., to determine sizes and thermal properties. We use all available photometric data of asteroids to derive their physical models by the lightcurve inversion method and compare the observed pole latitude distributions of all asteroids with known convex shape models with the simulated pole latitude distributions. We used classical dense photometric lightcurves from several sources and sparse-in-time photometry from the U.S. Naval Observatory in Flagstaff, Catalina Sky Survey, and La Palma surveys (IAU codes 689, 703, 950) in the lightcurve inversion method to determine asteroid convex models and their rotational states. We also extended a simple dynamical model for the spin evolution of asteroids used in our previous paper. We present 119 new asteroid models derived from combined dense and sparse-in-time photometry. We discuss the reliability of asteroid shape models derived only from Catalina Sky Survey data (IAU code 703) and present 20 such models. By using different values for a scaling parameter cYORP (corresponds to the magnitude of the YORP momentum) in the dynamical model for the spin evolution and by comparing synthetics and observed pole-latitude distributions, we were able to constrain the typical values of the cYORP parameter as between 0.05 and 0.6.Comment: Accepted for publication in A&A, January 15, 201

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US)

Kinase inhibitors for the treatment of inflammatory and autoimmune disorders

Drugs targeting inhibition of kinases for the treatment of inflammation and autoimmune disorders have become a major focus in the pharmaceutical and biotech industry. Multiple kinases from different pathways have been the targets of interest in this endeavor. This review describes some of the recent developments in the search for inhibitors of IKK2, Syk, Lck, and JAK3 kinases. It is anticipated that some of these compounds or newer inhibitors of these kinases will be approved for the treatment of rheumatoid arthritis, psoriasis, organ transplantation, and other autoimmune diseases

Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype

Purpose Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach. Methods Whole-genome copy-number findings in patients with melanoma predisposition syndrome congenital melanocytic nevus were extrapolated to a sporadic melanoma cohort. Functional effects of duplications in PPP2R3B were investigated using immunohistochemistry, transcriptomics, and stable inducible cellular models, themselves characterized using RNAseq, quantitative real-time polymerase chain reaction (qRT-PCR), reverse phase protein arrays, immunoblotting, RNA interference, immunocytochemistry, proliferation, and migration assays. Results We identify here a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. This encodes PR70, a regulatory unit of critical phosphatase PP2A. Duplications increase expression of PR70 in human nevus, and increased expression in melanoma tissue correlates with survival via a nonimmunological mechanism. PPP2R3B overexpression induces pigment cell switching toward proliferation and away from migration. Importantly, this is independent of the known microphthalmia-associated transcription factor (MITF)-controlled switch, instead driven by C21orf91. Finally, C21orf91 is demonstrated to be downstream of MITF as well as PR70. Conclusion This work confirms the power of a rare disease approach, identifying a previously unreported copy-number change predisposing to melanocytic neoplasia, and discovers C21orf91 as a potentially targetable hub in the control of phenotype switching