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

Inclusive Place-Making in Spartanburg, SC: Amplifying Latinx Voices through Community-Based Research

In response to a growing local interest in “place-making” work, our team developed and carried out a research project centered on the ideas of inclusive place, community, and health, with a focus on the inclusion of the growing Latinx community in the Spartanburg area. The project is a first step in what we imagine to be a long arc of community-based research and is in response to the desire of community collaborators for better information to inform their decision-making, particularly with regard to inclusion of Latinx residents. The long-term arc of the research will be shaped by ideas from community partners related to inclusivity; thriving and welcoming community spaces; health equity; and food access and is adaptable to a focus on particular areas or demographics within Spartanburg County. The goal of the present phase of research was to generate qualitative data (1) to inform the implementation of upcoming community projects; (2) to be available to community leaders as a complement to existing quantitative data about areas related to the research focus; (3) to inform the scope, design, and methods of other groups interested in doing related research work, including program evaluation or assessment. Our qualitative approach has sought to respect the “Don’t do anything for us without us” imperative for inclusive community work and aims to create a way to include and amplify the voices of those who will be affected by coming community projects, in informing the implementation of those projects

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

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

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

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

Investigation of 76Se(18O, 17O)75Se and 76Se(18O, 19F)75As transfer reactions at 15 MeV/u in a multi-channel approach within the NUMEN project

. - A full-comprehensive study of heavy-ion induced nuclear reac-tions is a powerful tool to characterize nuclear mean-field features as well as few-nucleon correlations in low-lying nuclear states. In this context, the investigation of 76Se(18O,17O)75Se and 76Se(18O,19F)75As transfer reactions was performed with the NUMEN project, aiming at providing data-driven information to constrain nu-clear structure models for the 76Se nucleus. This nucleus is under investigation since it is the daughter nucleus of 76Ge in the neutrinoless double beta decay (0 nu 1313) pro-cess. The experiment was performed at INFN-LNS where the 18O beam impinged the 76Se target and the reaction ejectiles were momentum analyzed by the MAGNEX magnetic spectrometer

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

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