cssi/SciSciGPT-SciSciNet huggingface dataset:
Diabetes, Fasting Glucose Levels, and Risk of Ischemic Stroke and Vascular Events: Findings from the Northern Manhattan Study (NOMAS)

OBJECTIVE —There is insufficient randomized trial data to support evidence-based recommendations for tight control of fasting blood glucose (FBG) among diabetic subjects in primary stroke prevention. We explored the relationship between FBG among diabetic subjects and risk of ischemic stroke in a multiethnic prospective cohort. RESEARCH DESIGN AND METHODS —Medical and social data and FBG values were collected for 3,298 stroke-free community residents: mean age ± SD was 69 ±10 years; 63% were women, 21% were white, 24% were black, and 53% were Hispanic; and follow-up was 6.5 years. Baseline FBG levels were categorized: 1 ) elevated FBG: history of diabetes and FBG ≥126 mg/dl (7.0 mmol/l); 2 ) target FBG: history of diabetes and FBG 3 ) no diabetes/reference group. Cox models were used to calculate hazard ratios (HRs) and 95% CI for ischemic stroke and vascular events. RESULTS —In the Northern Manhattan Study, 572 participants reported a history of diabetes and 59% ( n = 338) had elevated FBG. Elevated FBG among diabetic subjects was associated with female sex ( P P = 0.01), or no insurance ( P = 0.03). We detected 190 ischemic strokes and 585 vascular events. Diabetic subjects with elevated FBG (HR 2.7 [95% CI 2.0–3.8]) were at increased risk of stroke, but those with target FBG levels (1.2 [0.7–2.1]) were not, even after adjustment. A similar relationship existed for vascular events: elevated FBG (2.0 [1.6–2.5]) and target FBG (1.3 [0.9–1.8]. CONCLUSIONS —This prospective cohort study provides evidence for the benefits of tighter glucose control for primary stroke prevention.
On some Schrodinger and wave equations with time dependent potentials

The existence and uniqueness of solutions in the initial value problem for Schrodinger and wave equations in the presence of a (large) time dependent potential is studied. The usual Strichartz estimates for such linear evolutions are shown to hold true with optimal assumptions on the potentials. As a byproduct, one obtains a counterexample to the two dimensional double endpoint inhomogeneous Strichartz estimate.
Dysregulation of the fibroblast growth factor system in major depression

In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.
Global time optimal motions of robotic manipulators in the presence of obstacles

A practical method to obtain the global time optimal motions of robotic manipulators is presented. This method takes into account the nonlinear manipulator dynamics, actuator constraints, joint limits, and obstacles. Previously developed methods of optimizing manipulator motions along given paths and a local path optimization are utilized. A set of best paths is obtained first in a global search over the manipulator workspace, using graph search and hierarchical pruning techniques. These paths are used as initial conditions for a continuous path optimization to yield the global optimal motion. Examples of optimized motions of a six-degree-of-freedom manipulator, operating in a three-dimensional space with obstacles, are presented. >
A Social Values Analysis of Self–Other Differences in Decision Making Involving Risk

Three experiments tested our social values analysis of self–other differences in decision making under risk. In Experiment 1, we showed that people make riskier decisions for others in domains where risk taking is valued but not in those where risk is not valued. Experiment 2 documented that it is considered more inappropriate to make a risk-averse decision for another person than for oneself in situations where risk is valued. Experiment 3 showed that self–other differences in decision making occur even when there are no self–other differences in prediction and for decisions made for a typical student as well as for a friend. We use these results to argue that decision making for others is based predominantly on the perceived value placed on risk, leading to a norm for how to decide for others in situations where such a social value exists.
Autophagy and Intestinal Homeostasis

Nutrient absorption is the basic function that drives mammalian intestinal biology. To facilitate nutrient uptake, the host's epithelial barrier is composed of a single layer of cells. This constraint is problematic, as a design of this type can be easily disrupted. The solution during the course of evolution was to add numerous host defense mechanisms that can help prevent local and systemic infection. These mechanisms include specialized epithelial cells that produce a physiochemical barrier overlying the cellular barrier, robust and organized adaptive and innate immune cells, and the ability to mount an inflammatory response that is commensurate with a specific threat level. The autophagy pathway is a critical cellular process that strongly influences all these functions. Therefore, a fundamental understanding of the components of this pathway and their influence on inflammation, immunity, and barrier function will facilitate our understanding of homeostasis in the gastrointestinal tract.
Mantle helium in ground waters of eastern North America: Time and space constraints on sources

Mantle helium in continental environments is generally considered to be the result of active volcanism and/or active extension. The latest episodes of volcanism in northeastern North America are the track of the New England hotspot (95–190 Ma) and the closure of the Iapetus sea (before 300 Ma). Thus, the identification of mantle helium in young ground waters of central New England is counter to the conventional wisdom. On the basis of evaluation of helium evolution in emplaced magmas, we postulate an “aged” mantle source for the excess helium component in ground waters of central New England that is either (1) a local, near-surface–emplaced, gas-rich magma that has retained significant volatiles (e.g., in fluid inclusions) or (2) a deeply emplaced gas-rich magma with high initial 2 He/ 4 He (10 −5 ) and helium transport (with dispersion) through the crust over time. This gas-rich initial condition may support the concept of a volatile-enriched mantle wedge and thus explain the increased buoyancy flux of the New England hotspot as it traversed eastern North America, as has been suggested by others.
Quality of Life After Coronary Artery Bypass Surgery: Past Progress and Future Directions

Historically, morbidity and mortality have been the primary outcome measures in coronary artery bypass research. Limited health care resources have led to greater emphasis on cost as a primary outcome mea sure. These are each important measures, but they fail to directly assess what patients care about, which is their overall quality of life (QOL). When QOL is used as an outcome in medical research, it should encompass at a minimum the following domains: physical status, mental function, social interaction, and disease-specific measure. Fortunately, QOL assessment instruments already exist that are reliable, valid, and sensitive to change. This article describes how QOL is defined, what instruments are available, how they have been devel oped, and how they are selected. Next, QOL in the coronary artery bypass literature is reviewed. This in cludes both the large randomized trials as well as studies focusing solely on QOL. Finally, future directions for QOL as an outcome measure are examined.
Educators' Perceptions of Collaborative Planning Processes for Students With Disabilities

As schools emphasize accountability and academic progress for all students, professional collaboration is a critical aspect of planning accommodations and interventions that address the learning needs of diverse learners. To better understand collaborative processes, the authors investigated the nature of a collaborative planning experience for pairs of special and general education teachers. Teachers were taught the curriculum, rules, instruction, materials, and environment collaboration process (M. A. Prater, 2003) in which teachers compared the demands of the general education classroom with the strengths and limitations of the individual student. Results indicate that sharing common philosophies about educating students with disabilities is an important aspect of successful collaborative planning. Teachers who expressed common philosophies about educating students with disabilities completed the process together. The teachers who did not express similar philosophies completed the process separately.
Hyperclique pattern discovery

Existing algorithms for mining association patterns often rely on the support-based pruning strategy to prune a combinatorial search space. However, this strategy is not effective for discovering potentially interesting patterns at low levels of support. Also, it tends to generate too many spurious patterns involving items which are from different support levels and are poorly correlated. In this paper, we present a framework for mining highly-correlated association patterns called hyperclique patterns. In this framework, an objective measure called h-confidence is applied to discover hyperclique patterns. We prove that the items in a hyperclique pattern have a guaranteed level of global pairwise similarity to one another as measured by the cosine similarity (uncentered Pearson's correlation coefficient). Also, we show that the h-confidence measure satisfies a cross-support property which can help efficiently eliminate spurious patterns involving items with substantially different support levels. Indeed, this cross-support property is not limited to h-confidence and can be generalized to some other association measures. In addition, an algorithm called hyperclique miner is proposed to exploit both cross-support and anti-monotone properties of the h-confidence measure for the efficient discovery of hyperclique patterns. Finally, our experimental results show that hyperclique miner can efficiently identify hyperclique patterns, even at extremely low levels of support.
Reliable service discovery for network-centric systems

This paper describes a service-oriented architecture for network-centric operations that supports Reliable Service Discovery (RSD). We analyze several complementary mechanisms for improving the reliability of the service discovery process. These include distributed service registries with replication of registry entries, periodic revalidation of registry data with propagation of registry updates, and adaptive reconfiguration of the registry topology in response to changes in network membership and connectivity. We derive properties for each of these mechanisms that lead to optimal performance in the resourceconstrained environments typical of mobile ad hoc networks (MANETs). We then outline directions for further research, including a concept of adaptive intelligent registry proxies that can opportunistically employ peer-to-peer caching and sharing of registry information when it is appropriate from both the system perspective and the individual client perspective.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Factors Affecting the Perception of Interobject Distances in Virtual Environments

Two experiments collectively explored four factors that may influence people's judgments of exocentric (interobject) distances in virtual environments. Participants freely navigated in a simple virtual environment and repeatedly made magnitude estimations of exocentric distances. Distances were generally overestimated. An exponential model (Stevens' power law) fit the data, and exponent estimates were generally less than unity. Geometric field of view (GFOV) and the presence of error-corrective feedback were found to have the strongest effect on accuracy. In fact, distance perception was nearly veridical when made with an 80 deg. GFOV and when receiving feedback. Display type (head-mounted versus desktop) and the presence of additional perspective cues were less influential.
Insertion of dGMP and dAMP during in vitro DNA synthesis opposite an oxidized form of 7,8-dihydro-8-oxoguanine

Oxidative damage to DNA bases commonly resultsin the formation of oxidized purines, particularly 7,8-dihydro-8-oxoguanine (8-oxoG) and 7,8-dihydro-8-oxoadenine (8-oxoA), the former being a well-known mutagenic lesion. Since 8-oxoG is readily subject to further oxidation compared with normal bases, the insertion of a base during DNA synthesis opposite an oxidized form of 8-oxoG was investigated in vitro. A synthetic template containing a single 8-oxoG lesion was first treated with different one-electron oxidants or under singlet oxygen conditions and then subjected to primer extension catalyzed by Klenow fragment exo- (Kf exo-), calf thymus DNA polymerase alpha (pol alpha) or human DNA polymerase beta (pol beta). Consistent with previous reports, dAMP and dCMP are inserted selectively opposite 8-oxoG with all three DNA polymerases. Interestingly, oxidation of 8-oxoG was found to induce dAMP and dGMP insertion opposite the lesion by Kf exo- with transient inhibition of primer extension occurring at the site of the modified base. Furthermore, the lesion constitutes a block during DNA synthesis by pol alpha and pol beta. Experiments with an 8-oxoA-modified template oligonucleotide show that both 8-oxoA and an oxidized form of 8-oxoA direct insertion of dTMP by Kf exo-. Mass spectrometric analysis of 8-oxoG-containing oligonucleotides before and after oxidation with IrCl62-are consistent with oxidation of primarily the 8-oxoG site, resulting in formation of a guanidinohydantoin moiety as the major product. No evidence for formation of abasic sites was obtained. These results demonstrate that an oxidized form of 8-oxoG, possibly guanidinohydantoin, may direct misreading and misinsertion of dNTPs during DNA synthesis. If such a process occurred in vivo, it would represent a point mutagenic lesion leading to G-->T and G-->C transversions. However, the corresponding oxidized form of 8-oxoA primarily shows correct insertion of T during DNA synthesis with Kf exo-.
SPECIES DISCRIMINATION AND MORPHOLOGICAL RELATIONSHIPS OF KANGAROO RATS (DIPODOMYS) BASED ON THEIR DENTITION

Fossils of the Heteromyidae usually are distinguished using quantitative dental characters because of a lack of diagnostic qualitative characters. However, utility of these characters in addressing taxonomic questions is unclear. Teeth of 19 extant species of kangaroo rats (Dipodomys) were measured to determine if quantitative characters provided reliable separation of taxa and to what extent morphometric analyses revealed meaningful higher level relationships. A discriminant analysis correctly allocated >70% of specimens to their a priori species groups. Dimensions that were best able to separate taxa, as judged from a canonical variate analysis, were lengths of premolars and 1st lower molar. Squared Mahalanobis distances, canonical variate analysis, principal component analysis, cluster analysis, and minimum spanning trees supported morphological groupings including: D. nelsoni and D. spectabilis; D. compactus and D. ordii; D. merriami and D. nitratoides; and the 5 species D. agilis, D. heermanni, D. panamintinus, D. simulans, and D. stephensi. D. deserti and D. elator differed in their dental morphology from all other taxa. Overall, results closely paralleled those of previous workers, suggesting that quantitative dental characters can reliably distinguish heteromyid taxa and perhaps help elucidate higher level taxonomic relationships.
Fiscal Decentralization in Bulgaria's Early Transition

The paper reviews Bulgaria's inter-governmental finances and the process of fiscal decentralization during the early transition (1990-95) from centrally planned to a market economy. The paper discusses salient features and reform issues in tax assignments, inter-governmental relations, expenditure assignments, sub-national borrowing, and transfers. Based on Bulgaria's experience, the paper draws implications for other countries in transition from socialism.
Les préfaces des traducteurs des Anciens Canadiens: transformation du message

En 1863, Philippe Aubert de Gaspe publie Les Anciens Canadiens, roman qui deviendra le premier succes commercial du territoire aujourd’hui designe comme le Quebec. Au cours de l’histoire, cette œuvre sera traduite vers l’anglais a trois reprises. Fait notable, les retraductions des Anciens Canadiens sont accompagnees de prefaces redigees par les traducteurs. Dans sa preface, Charles G.D. Roberts, traducteur de la version anglaise publiee en 1890, vante les merites de l’œuvre d’Aubert de Gaspe, en plus d’expliquer que le roman est d’interet pour les Canadiens Anglais, car il leur permet de mieux comprendre leurs compatriotes francophones. Notons, toutefois, que Roberts ne fait aucunement mention de la premiere traduction. De son cote, Jane Brierley, auteure de la derniere traduction (1996), prend elle-meme l’initiative de produire une nouvelle version anglaise du roman. Dans sa preface, elle explique qu’une retraduction de l’ouvrage d’Aubert de Gaspe etait necessaire, car les deux traductions precedentes, dont elle offre l’analyse textuelle, n’etaient pas adequates. Elle affirme egalement que, forte d’avoir traduit les deux autres ouvrages de Gaspe, elle a su developper pour cet auteur une voix anglaise appropriee. Ainsi, nous mettrons en lumiere les notions clefs soulevees dans chacune des prefaces. A premiere vue, Roberts semble plutot mettre l’accent sur l’importance historique de l’œuvre de Gaspe et l’interet qu’elle represente pour les anglophones, alors que Brierley, pour sa part, justifie la necessite d’une retraduction. Il va sans dire qu’au su de leur lectorat potentiel, les deux traducteurs ont des preoccupations bien differentes.
Priorities of Care Among Older Adults in the Emergency Department: A Cross-sectional Study.

Objectives Emergency departments (EDs) are an increasingly important site of care for older adults, but little is known about the priorities of emergency care in this population. We sought to describe and rank priorities of care among older adults receiving care in the ED. Methods We conducted a cross-sectional study of cognitively intact patients aged 65 years and older receiving care in two U.S. EDs. Participants provided up to three open-ended responses to a single question asking what would make their ED visit successful, useful, or valuable. A literature review and patient responses were used to generate priority categories and larger metacategories. Each response was then assigned to one of the categories by independent reviewers. We report the percentage of patients identifying a priority in each category and metacategory and the relative weight of each category based on the frequency and order of priorities provided by patients. Results A total of 185 participants provided 351 priorities. Twenty-four categories and seven metacategories were identified. Sixty-two percent (N = 114) of participants reported at least one priority in the "evaluation, treatment, and outcomes" metacategory. Of these, the most common priorities included treatment of the medical problem (n = 37, 20%), accurate diagnosis (n = 36, 19%), competent staff and provider (n = 28, 15%), and desirable health outcome (n = 24, 13%). The second and third most common metacategories were "timely care" (n = 67, 36%), and "service" (n = 38, 21%). Nineteen patients (10%) expressed a desire to be discharged; one patient (1%) expressed a desire for admission. The ranking of weighted priorities were identical to the unweighted rank order by frequency. Conclusions Among a sample of cognitively intact older ED patients, the most common priorities were related to the accuracy and efficiency of the medical evaluation. These priorities should be considered by those attempting to improve the emergency care of older adults.
Cytologic survey for squamous cancer of the cervix in Honolulu, 1949-1962.

Abstract Over twelve years' experience in a free service laboratory sponsored by the Hawaii Cancer Society in Honolulu has been reviewed, with a detailed study of the squamous lesions of the cervix detected in that laboratory.
A Systematic Review of Self-Management Interventions for Inflammatory Bowel Disease.

Purpose To conduct a systematic review of self-management interventions for adults with inflammatory bowel disease (IBD) to (a) describe self-management skills in the interventions and (b) describe the effects of the interventions on the health-related outcomes measured. Design Systematic review of self-management interventions for adults with IBD using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methods The search was conducted using Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Proquest databases. Search terms were inflammatory bowel disease OR Crohn* disease OR ulcerative colitis AND self-management. We also used additional limits (adults ≥18 years of age and published in English). The self-management skills were organized according to Lorig and Holman's five self-management skills. Findings Six reports met the inclusion criteria. One intervention contained all five of the self-management skills. Most interventions contained two skills. Four studies demonstrated positive effects of self-management on disease activity. Two interventions revealed positive effects on disease-specific health-related quality of life (HRQOL), and one intervention revealed positive effects on generic HRQOL. One study showed positive effects of symptoms. Conclusions The interventions reviewed varied in the approaches, theoretical perspectives, self-management skills, and outcomes measured. Additional research is needed to understand which are the active components of self-management. Clinical Relevance Support for self-management skills is an important component of nursing care for people with IBD.
MnII/III Complexes as Promising Redox Mediators in Quantum-Dot-Sensitized Solar Cells

The advancement of quantum dot sensitized solar cell (QDSSC) technology depends on optimizing directional charge transfer between light absorbing quantum dots, TiO2, and a redox mediator. The nature of the redox mediator plays a pivotal role in determining the photocurrent and photovoltage from the solar cell. Kinetically, reduction of oxidized quantum dots by the redox mediator should be rapid and faster than the back electron transfer between TiO2 and oxidized quantum dots to maintain photocurrent. Thermodynamically, the reduction potential of the redox mediator should be sufficiently positive to provide high photovoltages. To satisfy both criteria and enhance power conversion efficiencies, we introduced charge transfer spin-crossover MnII/III complexes as promising redox mediator alternatives in QDSSCs. High photovoltages ∼1 V were achieved by a series of Mn poly(pyrazolyl)borates, with reduction potentials ∼0.51 V vs Ag/AgCl. Back electron transfer (recombination) rates were slower than Co(bpy)3, wher...
Demonstration of gate control of spin splitting in a high-mobility InAs/AlSb two-dimensional electron gas

Control of zero-field spin splitting is realized in a dual-gated high-quality InAs-AlSb two-dimensional electron gas. Magnetotransport experiments showed clean Shubnikov--de Haas oscillations down to low magnetic fields, and the gate-tuned electron mobility exceeded $700\phantom{\rule{0.16em}{0ex}}000\phantom{\rule{0.16em}{0ex}}\mathrm{c}{\mathrm{m}}^{2}/\mathrm{V}\phantom{\rule{0.16em}{0ex}}\mathrm{s}$. A clear beating effect was observed in magnetoresistance oscillations at large potential asymmetry between gates. Beat patterns due to zero-field spin splitting and other classes of transverse magnetoresistance oscillations were distinguished by temperature-dependent magnetoresistance measurements. Analysis of the magnetoresistance oscillations indicated that the zero-field spin splitting could be tuned via the Rashba effect while keeping the two-dimensional electron gas charge density constant.
Repair of dissection of the thoracic aorta. Evaluation of false lumen utilizing computed tomography.

During the period 1975 to 1980, 21 patients with thoracic aortic dissections underwent surgical treatment. The operative technique was resection and tube graft replacement of the segment of the aorta containing the entry point into the false channel. Eleven Type A and 10 Type B dissections were resected. The hospital survival rate was 95%. The single operative death occurred in a patient with an acute Type A dissection. Three patients had total resection of the dissected segment; three had clotted false lumina; five had distal anastomosis to true and false lumina; and 10 had distal anastomosis to the true lumen only, with proximal entry into the false lumen obliterated by incorporating both intimal and adventitial walls in a single suture line. The late survival rate was 95% (mean 32 months, range 8 to 63 months). No late ruptures occurred. Computed tomography (CT) with contrast enhancement was used to evaluate the aorta and any residual false lumen at follow-up. Seven of eight patients in whom obliteration was attempted and CT scans performed demonstrated persistence of false lumen perfusion; in six of the eight, preoperative angiograms were adequate for evaluation of false lumen runoff. Major vessels arose from the false lumen in all cases, except in the one patient in whom obliteration was later successful. This report demonstrates that there is persistence of false lumen perfusion in patients in whom obliteration is attempted, and the mechanism of this persistence is the presence of major vessel runoff. It suggests that the mechanism by which long-term survival is achieved is by resection of the segment of aorta containing the entry site, which is frequently the site of subsequent enlargement and rupture, rather than obliteration of the false channel.
Run-time support for parallel programs

The emergence of commercial multiprocessors has prompted computer scientists to take a closer look at parallel programming. Apart from the intrinsic limitations to parallelism imposed by algorithms, the key problem in developing a high-performance parallel programming system is the design of efficient run-time support code. This dissertation explores the issues related to the design and implementation of efficient run-time support code for parallel programs. These programs are written in procedural or imperative languages and are targeted to a shared-memory multiprocessor. The programming paradigms considered include both implicit and explicit program parallelism. Implicit parallelism is addressed in the form of parallel loops. In the case of explicit parallelism, new language constructs are presented that allow the denotation of parallel procedures. The design of efficient run-time support for these parallel programs is introduced as a microtasking run-time system. Two different microtasking run-time systems are described, one being a baseline system capable of supporting parallel loops, and the second being a more complex system capable of supporting both parallel loops and parallel procedures. An approach for interfacing this second run-time system design with existing multiprocessor operating systems is also provided. Three important factors that limit the performance of parallel programs are also studied: (1) load balancing; (2) run-time scheduling and synchronization; and (3) cache consistency overhead. Their impact on the performance of several parallel programs is assessed under a variety of conditions. Highly accurate interpreter-driven simulation of actual parallel program binaries is used to provide data for this study. The variables for these experiments include the algorithm used for run-time scheduling and the technique employed to enforce cache consistency. The experiments show that with appropriate language semantics, run-time scheduling and synchronization can be very efficient, leaving load balancing and cache consistency as the major sources of overhead. However, the tests also show that the parallel procedure programming model in some cases eliminates the negative effects of load imbalance. Furthermore, the tests indicate that the overhead associated with the more complex parallel procedure run-time system is equivalent to the baseline run-time system.
Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers.

// Milan Radovich 1,2,* , Patrick J. Kiel 1,2,* , Stacy M. Nance 1 , Erin E. Niland 1 , Megan E. Parsley 1 , Meagan E. Ferguson 1 , Guanglong Jiang 2 , Natraj R. Ammakkanavar 2 , Lawrence H. Einhorn 2 , Liang Cheng 2 , Mehdi Nassiri 2 , Darrell D. Davidson 2 , Daniel A. Rushing 2 , Patrick J. Loehrer 2 , Roberto Pili 2 , Nasser Hanna 2 , J. Thomas Callaghan 2 , Todd C. Skaar 2 , Paul R. Helft 2 , Safi Shahda 2 , Bert H. O’Neil 2 and Bryan P. Schneider 1,2 1 Indiana University Health Precision Genomics Program, Indianapolis, IN, USA 2 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA * These authors have contributed equally to this work Correspondence to: Bryan P. Schneider, email: // Keywords : precision medicine, personalized medicine, genomics, next-generation sequencing Received : June 07, 2016 Accepted : June 09, 2016 Published : July 15, 2016 Abstract Patients and Methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014–October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs . 3 of 57 (5.3%) treated with non-genomically guided therapy ( p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy ( p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs . 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.
Single-cell RNA-seq technology lends a hand into HSC ontogeny

Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the “panjunctional sarcoplasmic reticulum” hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.
Abstract 3857: Pharmacological reactivation of the tumor suppressor protein phosphatase 2A as a novel approach for the treatment of breast cancer

PP2A is a phosphatase that is functionally dysregulated and inactivated in over 50% of all breast cancers independent of histological type. While much attention has focused on oncogenic kinases as targets for cancer treatment, therapeutic targeting of phosphatases, the key negative regulators of these same signaling pathways, has remained largely unexplored. Starting with the observation that tricyclic neuroleptic drugs exert anticancer effects, our laboratory reverse engineered these drugs to generate a novel series of compounds that retain the anti-proliferative effects and favorable pharmacokinetic properties but are devoid of the undesirable central nervous system pharmacology of the parent drugs. It was subsequently demonstrated that these first generation novel derivatives exert anticancer effects in cell culture and xenograft models of cancer (without overt toxicity) by modulation of critical oncogenic signaling pathways. Recently, it was determined that the molecular basis of the actions of these novel derivatives is the activation of PP2A. Comprehensive profiling for activity in a panel of 240 cancer cell lines has shown that these first-in-class small molecule activators of PP2A (SMAPs) have significant anti-proliferative activity in breast cancer cell lines, and studies have been extended to disease relevant in vivo models (patient derived xenograft, GEMM, and traditional xenograft models). PP2A9s ability to negatively regulate a diverse set of oncogenic drivers in breast cancer means SMAPs are able to exert their effects through multiple biological mechanisms, swiftly disrupting cellular energetics and metabolism, inducing apoptosis and inhibiting proliferation. This will be exhibited through a variety of biological assays evaluating cell growth, apoptosis and changes in cellular metabolism. Target engagement assessed via western blotting demonstrates inhibition of PP2A targets critical for mediating SMAP activity, notably c-MYC and AKT. As a result, this research demonstrates SMAPs have potent activity in a wide variety of breast cancer contexts where response to current therapies is modest and limited by the development of treatment resistance. Thus, SMAPs may be a viable treatment option for high-risk populations of patients who do not respond to the current standard of care. This research strives to demonstrate that therapeutic reactivation of PP2A may represent a novel approach for breast cancer treatment and that these molecules may favorably impact the lives of women suffering from breast cancer. Citation Format: Caroline C. Farrington, Xiaoyan Wang, Mahnaz Janghorban, Juan Liang, Analisa Difeo, Rosalie Sears, Goutham Narla. Pharmacological reactivation of the tumor suppressor protein phosphatase 2A as a novel approach for the treatment of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3857.
Non-Adiabatic Photoprocesses of Fundamental Importance toChemistry: From Electronic Relaxation of DNA Bases to IntramolecularCharge Transfer in Electron Donor-Acceptor Molecules

Substituent effects on ultrafast electronic relaxation (internal conversion) of nucleobases and intramolecular charge transfer in electron donor-acceptor (EDA) molecules, containing benzonitrile and diphenylacetylene moieties, have been investigated using laser spectroscopy and simple ab initio methods. The results demonstrate the central role biradical states play in the nonadiabatic energy- and charge-transfer dynamics. Specifically, subpicosecond internal conversion characteristic of the naturally occurring nucleobases is effectively extinguished by covalent modification that prevents the out-of-plane deformation of the π π* singlet state into the twisted ethene-like structure of the biradical state. Similarly, the covalently modified EDA molecules, in which the biradical (π σ*) state of bent geometry lies substantially above the optically prepared ππ* state, do not exhibit intramolecular charge transfer even in highly polar solvents
Sleep Quantity and Quality during Acute Concussion: A Pilot Study.

STUDY OBJECTIVES: A number of subjective and objective studies provide compelling evidence of chronic postconcussion changes in sleep, yet very little is known about the acute effects of concussion on sleep quality and quantity. Therefore, the purpose of this prospective pilot study was to use actigraphy to examine the changes in sleep quality and quantity acutely following concussion at home rather than in a hospital or sleep laboratory. METHODS: Seventeen young adults (7 with acute concussion, 10 controls) were recruited for this study. All participants completed two 5-day testing sessions separated by 30 days from intake (controls) or day of injury (concussion). Participants wore actigraphs and kept a sleep journal. Sleep parameter outcomes included nighttime total sleep time (nTST), 24-h total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE). The coefficient of variation (CV) for each sleep parameter was computed for each session. RESULTS: nTST and TST CV was significantly greater in the concussion group. There is the additional indication that individuals with a concussion may require and obtain more sleep shortly after injury and subsequently have a shorter duration of sleep at 1 mo postinjury. This pattern was not seen in the measures of sleep quality (WASO, SE). CONCLUSION: Individuals with a concussion demonstrated increased nighttime sleep duration variability. This increase persisted at 1 mo postinjury and may be associated with previously documented self-reports of poor sleep quality lasting months and years after a concussion. Additionally, this increase may predispose individuals to numerous negative health outcomes if left untreated. Language: en
Hip Hop, Food Justice, and Environmental Justice

Until this book there has been little written about how food and ecology play a role in the school-to-prison pipeline. The school-to-prison pipeline is a systematic process which pushes out certain youth from school and into the juvenile justice system through discriminating policies. Most social justice activists and scholars throughout the USA focus on structural changes in the school and juvenile justice systems, such as eliminating high-stakes tests, the overrepresentation of Youth of Color in special education, school suspension, surveillance and police in schools, police brutality toward youth, mass incarceration of Youth of Color, abuse of medication, hiring more staff that are representative of the identities of the students, critical multiculturalism in the curriculum, professional development of teachers, and harsh sentencing (Nocella II, A. J., Parmar, P, & Stovall, D. (Eds.). From education to incarceration: Dismantling the school-to-prison pipeline. New York: Peter Lang Publishing, 2014).
Interactive iBook-Based Patient Education in a NeuroTrauma Clinic.

BACKGROUND Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Educational interventions may alleviate the burden of TBI for patients and their families. Interactive modalities that involve engagement with the educational material may enhance patient knowledge acquisition when compared to static text-based educational material. OBJECTIVE To determine the effects of educational interventions in the outpatient setting on self-reported patient knowledge, with a focus on iPad-based (Apple, Cupertino, California) interactive modules. METHODS Patients and family members presenting to a NeuroTrauma clinic at a tertiary care academic medical center completed a presurvey assessing baseline knowledge of TBI or concussion, depending on the diagnosis. Subjects then received either an interactive iBook (Apple) on TBI or concussion, or an informative pamphlet with identical information in text format. Subjects then completed a postsurvey prior to seeing the neurosurgeon. RESULTS All subjects (n = 152) significantly improved on self-reported knowledge measures following administration of either an iBook (Apple) or pamphlet (P < .01, 95% confidence interval [CI]). Subjects receiving the iBook (n = 122) performed significantly better on the postsurvey (P < .01, 95% CI), despite equivalent presurvey scores, when compared to those receiving pamphlets (n = 30). Lastly, patients preferred the iBook to pamphlets (P < .01, 95% CI). CONCLUSION Educational interventions in the outpatient NeuroTrauma setting led to significant improvement in self-reported measures of patient and family knowledge. This improved understanding may increase compliance with the neurosurgeon's recommendations and may help reduce the potential anxiety and complications that arise following a TBI.
Evanescent coupling between refillable ring resonators and laser-inscribed optical waveguides.

We investigated theoretically and experimentally the evanescent coupling between photonic waveguides of arbitrary shapes and refillable optical ring resonators on the same chip. The resonator hosts were designed to facilitate whispering gallery modes and etched by using a single-mask standard lithography process, whereas the waveguides were imprinted in the proximity of the ring resonator by using 3D ultrafast laser-writing technology. Finite element analysis in conjunction with coupled-mode theory revealed a coupling Q-factor (QC) of approximately 106. The polymer core ring resonator exhibited a loaded Q-factor (QT) as high as 5.4×104 and a free spectral range (FSR) of 406 pm at a center wavelength of 775 nm. Long-term stability of the ring resonator was repeatedly tested by examining the spectral location of optical resonances and the constancy of Q-factors and FSRs under ambient laboratory conditions for 1 month. We recorded consistent Q-factors and repeatable FSRs for all measurements. Renewability of the polymer core was demonstrated by removing and redepositing the polymer in the cavity, followed by measurements of Q-factors and FSRs. This work promises to enable reconfigurable and renewable photonic devices for on-chip lasers, 3D integrated optical signal processing, chip-scale molecular sensing, and the investigation of new optical phenomena.
Strategic Temporality on Social Media During the General Election of the 2016 U.S. Presidential Campaign

To date, little attention has been paid to the temporal nature of campaigns as they respond to events or react to the different stages of a political election -- what we define as strategic temporality. This article seeks to remedy this lack of research by examining campaign Facebook and Twitter messaging shifts during the 2016 U.S. Presidential general election. We used supervised machine-learning techniques to predict the types of messages that campaigns employed via social media and analyzed time-series data to identify messaging shifts over the course of the general election. We also examined how social media platforms and candidates' party affiliation shape campaign messaging. Results suggest differences exist in the types of campaign messages produced on different platforms during the general election. As election day drew closer, campaigns generated more calls-to-action and informative messages on both Facebook and Twitter. This trend existed in advocacy campaign messages as well, but only on Twitter. Both advocacy and attack tweets were posted more frequently around Presidential and Vice-Presidential debate dates.
Blueprint for an intestinal villus: Species-specific assembly required

Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger-like projections called villi is an important adaptation that ensures the massive surface area for nutrient contact that is required to meet metabolic demands. Each villus projection serves as a functional absorptive unit: it is covered by a simple columnar epithelium that is derived from endoderm and contains a mesodermally derived core with supporting vasculature, lacteals, enteric nerves, smooth muscle, fibroblasts, myofibroblasts, and immune cells. In cross section, the consistency of structure in the billions of individual villi of the adult intestine is strikingly beautiful. Villi are generated in fetal life, and work over several decades has revealed that villus morphogenesis requires substantial "crosstalk" between the endodermal and mesodermal tissue components, with soluble signals, cell-cell contacts, and mechanical forces providing specific dialects for sequential conversations that orchestrate villus assembly. A key part of this process is the formation of subepithelial mesenchymal cell clusters that act as signaling hubs, directing overlying epithelial cells to cease proliferation, thereby driving villus emergence and simultaneously determining the location of future stem cell compartments. Interestingly, distinct species-specific differences govern how and when tissue-shaping signals and forces generate mesenchymal clusters and control villus emergence. As the details of villus development become increasingly clear, the emerging picture highlights a sophisticated local self-assembled cascade that underlies the reproducible elaboration of a regularly patterned field of absorptive villus units. This article is categorized under: Vertebrate Organogenesis > From a Tubular Primordium: Non-Branched Comparative Development and Evolution > Organ System Comparisons Between Species Early Embryonic Development > Development to the Basic Body Plan.