Canonical Melnikov theory for diffeomorphisms

We study perturbations of diffeomorphisms that have a saddle connection between a pair of normally hyperbolic invariant manifolds. We develop a first-order deformation calculus for invariant manifolds and show that a generalized Melnikov function or Melnikov displacement can be written in a canonical way. This function is defined to be a section of the normal bundle of the saddle connection. We show how our definition reproduces the classical methods of Poincar\'{e} and Melnikov and specializes to methods previously used for exact symplectic and volume-preserving maps. We use the method to detect the transverse intersection of stable and unstable manifolds and relate this intersection to the set of zeros of the Melnikov displacement.Comment: laTeX, 31 pages, 3 figure

Dominant B-cell epitopes from cancer/stem cell antigen SOC2 recognized by serum samples from cancer patients

Cataloged from PDF version of article.Human sex determining region Y-box 2 (SOX2) is an important transcriptional factor involved in the pluripotency and stemness of human embryonic stem cells. SOX2 plays important roles in maintaining cancer stem cell activities of melanoma and cancers of the brain, prostate, breast, and lung. SOX2 is also a lineage survival oncogene for squamous cell carcinoma of the lung and esophagus. Spontaneous cellular and humoral immune responses against SOX2 present in cancer patients classify it as a tumor-associated antigen (TAA) shared by lung cancer, glioblastoma, and prostate cancer among others. In this study, B-cell epitopes were predicted using computer-assisted algorithms. Synthetic peptides based on the prediction were screened for recognition by serum samples from cancer patients using ELISA. Two dominant B-cell epitopes, SOX2:52-87 and SOX2:98-124 were identified. Prostate cancer, glioblastoma and lung cancer serum samples that recognized the above SOX2 epitopes also recognized the full-length protein based on Western blot. These B-cell epitopes may be used in assessing humoral immune responses against SOX2 in cancer immunotherapy and stem cell-related transplantation

Correlative analysis of structure and chemistry of LixFePO4 platelets using 4D-STEM and X-ray ptychography

Lithium iron phosphate (LixFePO4), a cathode material used in rechargeable Li-ion batteries, phase separates upon de/lithiation under equilibrium. The interfacial structure and chemistry within these cathode materials affects Li-ion transport, and therefore battery performance. Correlative imaging of LixFePO4 was performed using four-dimensional scanning transmission electron microscopy (4D-STEM), scanning transmission X-ray microscopy (STXM), and X-ray ptychography in order to analyze the local structure and chemistry of the same particle set. Over 50,000 diffraction patterns from 10 particles provided measurements of both structure and chemistry at a nanoscale spatial resolution (16.6-49.5 nm) over wide (several micron) fields-of-view with statistical robustness.LixFePO4 particles at varying stages of delithiation were measured to examine the evolution of structure and chemistry as a function of delithiation. In lithiated and delithiated particles, local variations were observed in the degree of lithiation even while local lattice structures remained comparatively constant, and calculation of linear coefficients of chemical expansion suggest pinning of the lattice structures in these populations. Partially delithiated particles displayed broadly core-shell-like structures, however, with highly variable behavior both locally and per individual particle that exhibited distinctive intermediate regions at the interface between phases, and pockets within the lithiated core that correspond to FePO4 in structure and chemistry.The results provide insight into the LixFePO4 system, subtleties in the scope and applicability of Vegards law (linear lattice parameter-composition behavior) under local versus global measurements, and demonstrate a powerful new combination of experimental and analytical modalities for bridging the crucial gap between local and statistical characterization.Comment: 17 pages, 4 figure

Kernel techniques for adaptive Monte Carlo methods

We introduce a general kernel-informed Monte Carlo algorithm family for fast sampling from Bayesian posterior distributions. Our focus is on the highly challenging Big Models regime, where posteriors often exhibit strong nonlinear correlations and the evaluation of the target density (and its gradient) is either analytically intractable or computationally expensive. To construct efficient sampling schemes in these cases, application of adaptive MCMC methods learning the target geometry becomes critical. We present how kernel methods can be embedded into the adaptive MCMC paradigm enabling to construct rich classes of proposals with attractive convergence and mixing properties. Our ideas are exemplified for three popular sampling techniques: Metropolis-Hastings, Hamiltonian Monte Carlo and Sequential Monte Carlo

One-neutron transfer reaction in the 18^{18}O + 48^{48}Ti collision at 275 MeV

The present article reports new data on the $^{48}$Ti($^{18}$O,$^{17}$O)$^{49}$Ti reaction at 275 MeV incident energy as part of the systematic research pursued within the NUMEN project. Supplementary measurements of the same reaction on $^{16}$O and $^{27}$Al targets were also performed in order to estimate the background arising from the use of a composite target (TiO$_{2}$ + $^{27}$Al). These data were analyzed under the same theoretical framework as those obtained with the titanium target in order to reinforce the conclusions of our analysis. Differential cross-section angular distribution measurements for the $^{17}$O$^{8+}$ ejectiles were performed in a wide angular range by using the MAGNEX large acceptance magnetic spectrometer. The experimental results were analyzed within the distorted-wave and coupled-channels Born Approximation frameworks. The optical potentials at the entrance and exit channels were calculated in a double folding approach adopting the S\~ao Paulo potential, and the spectroscopic amplitudes for the projectile and target overlaps were obtained from large-scale shell model calculations. The differential cross-sections are well-described by the theoretical calculations, where a weak coupling to collective excitations of projectile and target is inferred. The sensitivity of transfer cross-sections on different model spaces adopted in nuclear structure calculations, is also discussed

Novel Exon of Mammalian ADAR2 Extends Open Reading Frame

Background: The post-transcriptional processing of pre-mRNAs by RNA editing contributes significantly to the complexity of the mammalian transcriptome. RNA editing by site-selective A-to-I modification also regulates protein function through recoding of genomically specified sequences. The adenosine deaminase ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2 function in mice leads to a phenotype of epilepsy and premature death. Although A-to-I RNA editing is known to be subject to developmental and cell-type specific regulation, there is little knowledge regarding the mechanisms that regulate RNA editing in vivo. Therefore, the characterization of ADAR expression and identification of alternative ADAR variants is an important prerequisite for understanding the mechanisms for regulation of RNA editing and the causes for deregulation in disease. Methodology/Principal Findings: Here we present evidence for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by 49 amino acids through the utilization of an exon located 18 kilobases upstream of the previously annotated first coding exon and driven by a candidate alternative promoter. Interestingly, the 49 amino acid extension harbors a sequence motif that is closely related to the R-domain of ADAR3 where it has been shown to function as a basic, single-stranded RNA binding domain. Quantitative expression analysis shows that expression of the novel ADAR2 splice variant is tissue specific being highest in the cerebellum

One-proton transfer reaction for the O 18 + Ti 48 system at 275 MeV

Single-nucleon transfer reactions are processes that selectively probe single-particle components of the populated many-body nuclear states. In this context, recent efforts have been made to build a unified description of the rich nuclear spectroscopy accessible in heavy-ion collisions. An example of this multichannel approach is the study of the competition between successive nucleon transfer and charge exchange reactions, the latter being of particular interest in the context of single and double beta decay studies. To this extent, the one-proton pickup reaction Ti48(O18,F19)Sc47 at 275 MeV was measured for the first time, under the NUMEN experimental campaign. Differential cross-section angular distribution measurements for the F19 ejectiles were performed at INFN-LNS in Catania by using the MAGNEX large acceptance magnetic spectrometer. The data were analyzed within the distorted-wave and coupled-channels Born approximation frameworks. The initial and final-state interactions were described adopting the São Paulo potential, whereas the spectroscopic amplitudes for the projectile and target overlaps were derived from shell-model calculations. The theoretical cross sections are found to be in very good agreement with the experimental data, suggesting the validity of the optical potentials and the shell-model description of the involved nuclear states within the adopted model space

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

The NUMEN heavy ion multidetector for a complementary approach to the neutrinoless double beta decay

Neutrinos are so far the most elusive known particles, and in the last decades many sophisticated experiments have been set up in order to clarify several questions about their intrinsic nature, in particular their masses, mass hierarchy, intrinsic nature of Majorana or Dirac particles. Evidence of the Neutrinoless Double-Beta Decay (NDBD) would prove that neutrinos are Majorana particles, thus improving the understanding of the universe itself. Besides the search for several large underground experiments for the direct experimental detection of NDBD, the NUMEN experiment proposes the investigation of a nuclear mechanism strongly linked to this decay: the Double Charge Exchange reactions (DCE). As such reactions share with the NDBD the same initial and final nuclear states, they could shed light on the determination of the Nuclear Matrix Elements (NMEs), which play a relevant role in the decay. The physics of DCE is described elsewhere in this issue, while the focus of this paper will be on the challenging experimental apparatus currently under construction in order to fulfil the requirements of the NUMEN experiment. The overall structure of the technological improvement to the cyclotron, along with the newly developed detection systems required for tracking and identifying the reaction products and their final excitation level are described