Hundred photon microwave ionization of Rydberg atoms in a static electric field

We present analytical and numerical results for the microwave excitation of nonhydrogenic atoms in a static electric field when up to 1000 photons are required to ionize an atom. For small microwave fields, dynamical localization in photon number leads to exponentially small ionization while above quantum delocalization border ionization goes in a diffusive way. For alkali atoms in a static field the ionization border is much lower than in hydrogen due to internal chaos.Comment: revtex, 4 pages, 5 figure

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory

Neurotensin Receptor 3/Sortilin Contributes to Tumorigenesis of Neuroendocrine Tumors Through Augmentation of Cell Adhesion and Migration

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels of NTSR3/sortilin were noted in the majority of human clinical NETs (n = 21) by immunohistochemical analyses compared with normal tissues (n = 12). Expression of NTS and NTSR3/sortilin was also noted in all tested NET cell lines. In addition, small interfering RNA–mediated knockdown of NTSR3/sortilin decreased cell number without alteration of cell cycle progression and apoptosis induction in NET cell lines BON and QGP-1. Moreover, silencing of NTSR3/sortilin significantly suppressed cell adhesion and cell migration with inhibition of focal adhesion kinase and Src phosphorylation in the NET cells. Our results demonstrate increased expression of NTSR3/sortilin in NET patient tissues and a critical role of NTSR3/sortilin on NET cell adhesion and migration suggesting that NTSR3/sortilin contributes to NET tumorigenesis

Influence of goals on modular brain network organization during working memory

IntroductionTop-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM.MethodsHere, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity–a measure of brain sub-network segregation–that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant).ResultsFirst, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance.DiscussionThese results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM

Differential Expression and Tumorigenic Function of Neurotensin Receptor 1 in Neuroendocrine Tumor Cells

Neurotensin (NTS), localized predominantly to the small bowel, stimulates the growth of a variety of cancers, including neuroendocrine tumors (NETs), mainly through its interaction with the high-affinity NTS receptor 1 (NTSR1). Here, we observed increased expression of NTSR1 in almost all tested clinical NET samples, but not in normal tissues. Through RT-PCR analysis, we found that the expression of NTSR1 and NTSR2 was either variable (NTSR1) or absent (NTSR2) in human NET cell lines. In contrast, NTSR3 and NTS were expressed in all NET cells. Treatment with 5-aza-2\u27-deoxycytidine, a demethylating agent, increased levels of NTSR1 and NTSR2 suggesting that DNA methylation contributes to NTSR1/2 expression patterns, which was confirmed by methylation analyses. In addition, we found that knockdown of NTSR1 decreased proliferation, expression levels of growth-related proteins, and anchorage-independent growth of BON human carcinoid cells. Moreover, stable silencing of NTSR1 suppressed BON cell growth, adhesion, migration and invasion. Our results show that high expression of NTSR1 is found in clinical NETs and that promoter methylation is an important mechanism controlling the differential expression of NTSR1 and silencing of NTSR2 in NET cells. Furthermore, knockdown of NTSR1 in BON cells suppressed oncogenic functions suggesting that NTSR1 contributes to NET tumorigenesis

Exploring youth and caregiver preferences for asthma education video content

This study examines: 1) whether youth and their caregivers have different preferences for asthma education video topics and 2) if education topic preferences vary by youth and caregiver sociodemographic characteristics

A learning health systems approach to integrating electronic patient-reported outcomes across the health care organization

Introduction: Foundational to a learning health system (LHS) is the presence of a data infrastructure that can support continuous learning and improve patient outcomes. To advance their capacity to drive patient-centered care, health systems are increasingly looking to expand the electronic capture of patient data, such as electronic patient-reported outcome (ePRO) measures. Yet ePROs bring unique considerations around workflow, measurement, and technology that health systems may not be poised to navigate. We report on our effort to develop generalizable learnings that can support the integration of ePROs into clinical practice within an LHS framework. Methods: Guided by action research methodology, we engaged in iterative cycles of planning, acting, observing, and reflecting around ePRO use with two primary goals: (1) mobilize an ePRO community of practice to facilitate knowledge sharing, and (2) establish guidelines for ePRO use in the context of LHS practice. Multiple, emergent data collection activities generated generalizable guidelines that document the tangible best practices for ePRO use in clinical care. We organized guidelines around thematic areas that reflect LHS structures and stakeholders. Results: Three core thematic areas (and 24 guidelines) emerged. The theme of governance reflects the importance of leadership, knowledge management, and facilitating organizational learning around best practice models for ePRO use. The theme of integration considers the intersection of workflow, technology, and human factors for ePROs across areas of care delivery. Lastly, the theme of reporting reflects critical considerations for curating data and information, designing system functions and interactions, and presentation of ePRO data to support the translation of knowledge to action. Conclusions: The guidelines produced from this work highlight the complex, multidisciplinary nature of implementing change within LHS contexts, and the value of action research approaches to enable rapid, iterative learning that leverages the knowledge and experience of communities of practice

Effect of Laparoscopic Adjustable Gastric Banding on Metabolic Syndrome and Its Risk Factors in Morbidly Obese Adolescents

We examined the effect of laparoscopic adjustable gastric banding (LAGB) on weight loss, inflammatory markers, and components of the Metabolic Syndrome (MeS) in morbidly obese adolescents and determined if those with MeS lose less weight post-LAGB than those without. Data from 14–18 yr adolescents were obtained at baseline, 6 and 12 months following LAGB. Significant weight loss and improvements in MeS components were observed 6 months and one year following LAGB. The incidence of MeS declined 56.8% after 6 months and 69.6% after 12 months. There was no significant difference in amount of weight lost post-LAGB between those with and without MeS at either timepoint. Correlations between change in weight parameters and components of MeS in those with and without MeS at baseline were examined and found to vary by diagnostic category. LAGB is effective for short-term improvement in weight, inflammatory markers, and components of MeS in morbidly obese adolescents

c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae.

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization

G2A Signaling Dampens Colitic Inflammation via Production of IFN-γ

Proinflammatory consequences have been described for lysophosphatidylcholine, a lipid product of cellular injury, signaling via the G protein–coupled receptor G2A on myeloid and lymphoid inflammatory cells. This prompted the hypothesis that genetic deletion of G2A would limit intestinal inflammation in a mouse model of colitis induced by dextran sodium sulfate. Surprisingly, G2A2/2 mice exhibited significantly worsened colitis compared with wild-type mice, as demonstrated by disease activity, colon shortening, histology, and elevated IL-6 and IL-5 in colon tissues. Investigation of inflammatory cells recruited to inflamed G2A2/2 colons showed significantly more TNF-a+ and Ly6ChiMHCII2 proinflammatory monocytes and eosinophils than in wild-type colons. Both monocytes and eosinophils were pathogenic as their depletion abolished the excess inflammation in G2A2/2 mice. G2A2/2 mice also had less IFN-g in inflamed colon tissues than wild-type mice. Fewer CD4+ lymphocytes were recruited to inflamed G2A2/2 colons, and fewer colonic lymphocytes produced IFN-g upon ex vivo stimulation. Administration of IFN-g to G2A2/2 mice during dextran sodium sulfate exposure abolished the excess colitic inflammation and reduced colonic IL-5 and eosinophil numbers to levels seen in wild-type mice. Furthermore, IFN-g reduced the numbers of TNF-a+ monocyte and enhanced their maturation from Ly6ChiMHCII2 to Ly6CintMHCII+ . Taken together, the data suggest that G2A signaling serves to dampen intestinal inflammation via the production of IFN-g, which, in turn, enhances monocyte maturation to a less inflammatory program and ultimately reduces eosinophil-induced injury of colonic tissues