cssi/SciSciGPT-SciSciNet huggingface dataset:
Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF.

Eosinophils contribute to immune regulation and wound healing/fibrosis in various diseases, including asthma. Growing appreciation for the role of activin A in such processes led us to hypothesize that eosinophils are a source of this transforming growth factor-s superfamily member. Tumor necrosis factor-α (TNF) induces activin A by other cell types and is often present at the site of allergic inflammation along with the eosinophil-activating common s (sc) chain-signaling cytokines (interleukin (IL)-5, IL-3, granulocyte-macrophages colony-stimulating factor (GM-CSF)). Previously, we established that the combination of TNF plus a sc chain-signaling cytokine synergistically induces eosinophil synthesis of the remodeling enzyme matrix metalloproteinase-9. Therefore, eosinophils were stimulated ex vivo by these cytokines and in vivo through an allergen-induced airway inflammatory response. In contrast to IL-5+TNF or GM-CSF+TNF, the combination of IL-3+TNF synergistically induced activin A synthesis and release by human blood eosinophils. IL-3+TNF enhanced activin A mRNA stability, which required sustained signaling of pathways downstream of p38 and extracellular signal-regulated kinase mitogen-activated protein kinases. In vivo, following segmental airway allergen challenge of subjects with mild allergic asthma, activin A mRNA was upregulated in airway eosinophils compared with circulating eosinophils, and ex vivo, circulating eosinophils tended to release more activin A in response to IL-3+TNF. These data provide evidence that eosinophils release activin A and that this function is enhanced when eosinophils are present in an allergen-induced inflammatory environment. Moreover, these data provide the first evidence for posttranscriptional control of activin A mRNA. We propose that an environment rich in IL-3+TNF will lead to eosinophil-derived activin A, which has an important role in regulating inflammation and/or fibrosis.
Abstract 4381: High efficacy of T-LAK cell-originated protein kinase inhibitor in acute myeloid leukemia with FLT3-ITD mutation

The internal tandem duplication (FLT3-ITD) a gain-of-function mutation of FLT3, is associated with poor outcome in acute myeloid leukemia (AML). The use of FLT3 inhibitors currently undergoing clinical investigation has not yet improved overall survival. Therefore, novel therapies are needed. T-LAK cell-originated protein kinase (TOPK), a serine-threonine protein kinase, is highly expressed and associated with an aggressive cancer phenotype, but is hardly detectable in normal tissues. Here, we investigate TOPK in AML and demonstrate that it is highly expressed in most AML cell lines and some primary blasts, but is not detected in CD34+ cells of healthy donors. MV4-11 and U937 cells transfected with TOPK-siRNA showed significant decrease in cell viability (∼70%, P Treatment of 10 AML cell lines with OTS514 showed that FLT3 mutated cell lines were significantly more sensitive (IC5020nM). Annexin/PI staining showed 80% and 70% increase in apoptosis in FLT3-ITDmut cells (MV4-11 and MOLM13) treated with OTS514 (40nM; 48hrs). In contrast, only 40% and 10% apoptosis was observed in FLT3wt cells (U937 and KG1, respectively) treated under the same conditions. Additionally, cell cycle analysis in cells treated with OTS514 (20nM; 24 and 48 hrs) showed a dramatic decrease of S phase (∼98%; P = 0.003) in MV4-11 but only 70% (P Importantly, OTS514 treatment decreased cell viability and increased cell differentiation and apoptosis in primary blasts from pts relapsed after FLT3 inhibitor treatment (AC220). Furthermore, using a MV4-11-engrafted mouse model, we found that mice treated with 7.5mg/kg IV every day for 3 weeks survived significantly longer than vehicle treated mice (median survival 46 vs 29, P In conclusion, TOPK inhibitor exhibits preferential activity in FLT3-ITDmut AML, partially via inhibition of FLT3 expression. Thus, OTS514 represents new targeted therapy for this adverse risk subset of AML. Citation Format: Houda Alachkar, Martin Mutonga, Jae-Hyun Park, Gregory Malnassy, Alex Woods, Gordana Raca, Olatoyosi M. Odenike, Naofumi Takamatsu, Takashi Miyamoto, Shoji Hisada, Yo Matsuo, Wendy Stock, Yusuke Nakamura. High efficacy of T-LAK cell-originated protein kinase inhibitor in acute myeloid leukemia with FLT3-ITD mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4381. doi:10.1158/1538-7445.AM2015-4381
Strain Hardening Behaviors of Fe-11Mn-4Al-0. 2C Steels

A new quenching-tempering heat treatment method was adopted for the Fe-11Mn coldrolled steels which yielded a duplex microstructure consisting of ferrite and austenite when the samples were quenched in the range of 700 ~ 800 ℃,leading to good combinations of tensile strength(920 ~ 1 150 MPa) and elongation(35% ~ 65%).The volume fraction of austenite of the cold-rolled samples before and after the tensile tests was analyzed through XRD,and it was evidenced that TRIP effects occurred during the deformation.The strain hardening behavior during the tensile tests was studied.It proved that the optimized amount of ferrite and grain size of austenite made the TRIP effects occur at the appropriate time,therefore excellent mechanical properties were obtained.
Epidemiological Analysis of Notifiable Infectious Diseases in Hongze County from 2004 to 2008

Objective To comprehension the epidemic characteristics of notif iable infectious diseases from 2004 to 2008 in Hongze County, Jiangsu Province, and to provide the basis for the formulation of targeted prevention and control meansures.Methods The data of directy onlone reporting and annual report of notif iable infectious diseases were counted and analyzed with descriptive epidemiology.Results 3418 cases of notif iable infectious diseases were reported from 2004 to 2008 in Hongze country.There was 0 case of Category A .There were 2162 cases in 15 kinds of notif iable infectious diseases belonged to Category B.There were 442 cases in 4 kinds belonged to Category C.The tuberculosis is one of the most commom and vulnerable diseases, accounting for 43.15% of the various infectious diseases.Viral hepatitis accounted for 24.58%, mumps accounted for 14.66%, gonorrhea accounted for 3.72% and bacillary dysentery accounted for 3.42%.Conclusion Tuberculosis, hepatitis, mumps, gonorrhea, bacillary dysentery was the focus of prevention and control.
Erythropoietin stimulates phosphorylation of eIF-4E and identification of a 37-kD phosphoprotein that binds mRNA caps in erythroblasts

To explore the mechanism of erythropoietin action on differentiation of erythroblasts, we have examined its effect on regulating phosphorylation of the 25-kD mRNA cap binding protein (eIF-4E). Erythroblasts from the spleens of mice infected with the anemia strain of Friend virus (FVA cells) were studied. Erythropoietin stimulated phosphorylation of eIF-4E in FVA cells within 30 minutes, and this effect was maximal at 60 minutes. Phosphoamino acid analysis and tryptic phosphopeptide map analysis of eIF-4E isolated from both control and erythropoietin-treated cells identified a predominant phosphopeptide containing phosphoserine. However, when cells were incubated with 1 muM okadaic acid, eIF-4E was phosphorylated on both serine and threonine residues and three additional tryptic phosphopeptides were detected. We also identified a 37-kD phosphoprotein (pp37) that bound specifically to the m7GTP cap structure and coimmunoprecipitated with eIF-kD protein was phosphorylated on both serine and threonine residues. These results indicate that phosphorylation of eIF-4E is a target in erythropoietin-initiated signal transduction events and that this phosphorylation precedes observable effects of erythropoietin on macromolecular biosynthesis. Although of pp37 remains to be studied, it may represent a developmentally regulated mRNA cap binding protein.
Laparoscopic Repair of Abdominal Wall Hernias

The hernia is approached from within the peritoneum, reduced, and repaired with an intraperitoneal onlay of permanent mesh. This mesh is then secured to the abdominal wall with transfascial fixation sutures placed through the entire abdominal wall. The mesh overlaps the healthy fascia by at least 5 cm in every direction.
Diet and Breeding Seasonality among a Population of Sharp-Tailed Munias, Lonchura striata, in Malaysia

From April 1975 through March 1977, the food habits and breeding seasonality of a population of Sharp-tailed Munias (Lonchura striata) were studied in northwestern peninsular Malaysia. The abundance of munias on the study area varied in accordance with the 6-month rice-growing cycle there. The population peaked in March and September when juvenile birds were most numerous and when rice was most plentiful. Field observations and stomach analyses showed that the munias ate rice and the green filamentous alga, Spirogyra, almost exclusively. The primary periods of algae eating occurred in January and June-August, coinciding with the munias' two peak periods of reproductive activity, as determined by gonadal examination. Ap- parently munias on the study area ate Spirogyra as a source of protein to enable them to become physiologically ready for breeding, much as other tropical bird species eat insects. Thus, unlike other species, Sharp-tailed Munias' breeding seasonality is determined by manmade cycles of rice cultivation rather than by natural cycles of rain and insect abundance. Received 25 June 1979, accepted 9 October 1979. THE Sharp-tailed Munia (Lonchura striata) is a small (10-12 g), rather nondescript estrildid distributed from India through Indochina to the Malay Peninsula and Su- matra. In Malaysia it is one of several bird species that regularly causes considerable damage to the rice crop. In lowland rice-growing regions, this species is very abun- dant and nests in close association with humans, favoring small fruit trees and garden shrubs as nest sites. The species is monogamous and both parents share in the nesting duties (Avery 1978). Sharp-tailed Munias are not restricted to the low- lands; they also frequent scrub, orchards, plantations, river banks, roadsides, forest trails, and jungle clearings, ranging from sea level to elevations of 2,000 m (Medway and Wells 1976). The purpose of this study was to examine the food habits and time of breeding among Sharp-tailed Munias in relation to local rice-growing practices. I know of no previous field studies of this species, although a domesticated race, the Bengalese Finch, has been studied extensively in captivity (e.g. Eisner 1960, 1963; Slater 1967; Suzuki 1977). Wells (1966) examined the molt and gonadal cycles of three other Malaysian species of Lonchura and concluded that they have adopted a nomadic, opportunistic breeding strategy that ensures at least part of the population is ready to breed whenever environmental conditions permit. The results presented here suggest that the population of L. striata I studied was sedentary, had two distinct breeding seasons annually that coincided with local rice seasons, and exploited per- iodic blooms of protein-rich algae to supplement the breeding season diet.
Zinc Oxide Based Plasmonic Multilayer Resonator: Localized and Gap Surface Plasmon in the Infrared

Using alternative plasmonic materials, we experimentally demonstrate gap plasmon resonances in metal–insulator–metal nanostructures in the near- and mid-infrared wavelength regions utilizing gallium doped zinc oxide as the metallic component and undoped zinc oxide as the dielectric. We show that similar to metal–insulator–metal resonators previously demonstrated with noble metals, the layered transparent conducting oxide nanodisks support gap surface plasmon resonances characterized by highly confined electromagnetic fields in the dielectric gap. Such resonances can be tailored to desired values by varying the dielectric-layer thickness. Utilizing these observed gap plasmon resonance, we examine the potential of our structure for sensing applications by measuring the surface enhanced infrared absorption of an octadecanethiol layer. The layered nanostructure can detect very weak absorption resonances in nanoscale volumes of absorbing material deposited over the nanodisk resonator.
Current NEXRAD Cannot Reliably Enable Safe Flight Around Heavy Weather

ABSTRACTObjective: We wished to assess whether current-generation in-cockpit looping Next-Generation Radar (NEXRAD) can reliably enable safe flight around severe (“heavy”) convective weather.Background: Numerous studies suggest that estimating the closest point of approach (CPA) to heavy weather is difficult, and that current in-cockpit NEXRAD may be intrinsically inadequate for the task.Method: To investigate theoretically, we first examined the visual information present in looping NEXRAD. This predicted inherent task difficulty. Next, to investigate empirically, we developed a mathematical model of an “ideal storm,” generated a looping NEXRAD-type part-task simulation, and tested 21 general aviation (GA) pilots to measure effects of weather system depth (19 vs. 40 nm), and the opening and closing of gaps at various closure rates between cells (14, 7, 0, 7, 14 kt).Results: For the values tested, weather system depth had no significant effect on clearance from heavy weather (>40 dBZ reflectivity). Howeve...
LANDSAT-8 OPERATIONAL LAND IMAGER CHANGE DETECTION ANALYSIS

This paper investigated the potential utility of Landsat-8 Operational Land Imager (OLI) for change detection analysis and mapping application because of its superior technical design to previous Landsat series. The OLI SVM classified data was successfully classified with regard to all six test classes (i.e., bare land, built-up land, mixed trees, bushes, dam water and channel water). OLI support vector machine (SVM) classified data for the four seasons (i.e., spring, autumn, winter, and summer) was used to change detection results of six cases: (1) winter to spring which resulted reduction in dam water mapping and increases of bushes; (2) winter to summer which resulted reduction in dam water mapping and increase of vegetation; (3) winter to autumn which resulted increase in dam water mapping; (4) spring to summer which resulted reduction of vegetation and shallow water; (5) spring to autumn which resulted decrease of vegetation; and (6) summer to autumn which resulted increase of bushes and vegetation . OLI SVM classified data resulted higher overall accuracy and kappa coefficient and thus found suitable for change detection analysis.
Quality of Pharmacist-Managed Anticoagulation Therapy in Long-Term Ambulatory Settings: A Systematic Review.

Objective: To perform a systematic review to evaluate the quality of warfarin anticoagulation control in outpatient pharmacist-managed anticoagulation services (PMAS) compared with routine medical care (RMC). Data Sources: MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, and Cochrane CENTRAL, from inception to May 2017. Search terms employed: (“pharmacist-managed” OR “pharmacist-provided” OR “pharmacist-led” OR “pharmacist-directed”) AND (“anticoagulation services” OR “anticoagulation clinic” OR “anticoagulation management” OR “anticoagulant care”) AND (“quality of care” OR “outcomes” OR “bleeding” OR “thromboembolism” OR “mortality” OR “hospitalization” OR “length of stay” OR “emergency department visit” OR “cost” OR “patient satisfaction”). Study Selection and Data Extraction: Criteria used to identify selected articles: English language; original studies (comments, letters, reviews, systematic reviews, meta-analyses, editorials were excluded); warfarin use; outpatient setting; comparison group present; time in th...
The story of Your Life: A Process Perspective On Narrative and Emotion in Adult Development

Publisher Summary Adult development is one of the few fields in American psychology that has traditionally embraced the collection and analysis of individual's narrative accounts of their lives. This chapter discusses newer perspectives on the relationship of these narratives to adult development. It suggests that an individual's narrative accounts play a major role in the construction and understanding of these stages. By drawing on a personological theory of identity and social construction theories of both narrative and affect, the chapter describes different process approaches that demonstrate how life stories reveal and define the developmental and affective challenges of adult life. Each of these approaches has generated a new body of empirical research that has broadened and deepened understanding of the psychosocial “stages” of identity, intimacy, generativity, and ego integrity.
End-of-Life Care/Pain Management/Palliative

Palliative care is specialized medical care for individuals living with serious and often terminal illness. It employs an interdisciplinary approach to provide relief from the symptoms and stress of a serious illness. The goal of palliative care is to improve quality of life for both the patient and the family. Symptoms, such as shortness of breath, constipation, nausea, and pain in addition to other symptoms, are closely managed to help relieve suffering and discomfort. Hospice care is a type of palliative care, but not all palliative care is hospice care. There are four levels of hospice care. General physicians should be equipped to deliver basic palliative care and initiate advance care planning.
Hodgkin’s and Non-Hodgkin’s Lymphoma

Delineation and field setup for radiation therapy for both Hodgkin’s and ­non-Hodgkin’s lymphoma depend on the origin of the disease, the use and response to systemic chemotherapy, as well as the extent of disease.
Flocked fabrics and structures

Flocked articles are manufactured by various flocking techniques. Fiber coating (flocking) involves applying flock fibers on uncured adhesive-coated substrate surfaces by applying an electrostatic driving force on charged flock fibers. Flock fibers are finely cut natural or manufactured synthetic fibers with electrically conductive surface finishes. Flocked materials and products are applied in numerous fields such as upholstery, toys and crafts, jewelry display backings, the clothing industry, the automotive industry, carpets and technical textiles, because of their visual, technical and economical advantages. This chapter discusses electrostatic flocking theory, flock fiber preparation, flocking adhesives, flocking processes, flocked products and market trends.
Exercise Testing in Cardiac Rehabilitation

Functional exercise testing provides important physiologic information in patients in whom the diagnosis of ischemic heart disease has already been established. Peak workload, hemodynamic response to exercise, and ischemic threshold can all be quantified precisely, and these data can be utilized in the formulation of an individualized exercise prescription.
Gustation and Olfaction: The Importance of Place and Time

Animals can smell odors from the external environment or from their mouth via two routes: orthonasal and retronasal, respectively. Little is known about how the brain processes orthonasal and retronasal odors associated with taste, but a new study has revealed an important role for the gustatory cortex in such odor processing.
Characterizing and Simulating the Movement of Late-Instar Gypsy Moth (Lepidoptera: Erebidae) to Evaluate the Effectiveness of Regulatory Practices.

The European gypsy moth, Lymantria dispar L., is an invasive insect in North America that feeds on over 300 species of trees and shrubs and occasionally causes extensive defoliation. One regulatory practice within quarantine zones to slow the spread of this insect recommends that wood products (e.g., logs, pulpwood) originating from quarantine areas are staged within 100 foot-radius buffer zones devoid of host vegetation before transport outside the quarantine boundary. Currently, there are little data underpinning the distance used. We conducted field experiments in Wisconsin to assess buffer zone efficacy in reducing risk of larval gypsy moth encroachment on wood staging areas. We released late-instar gypsy moth larvae in groups around the perimeter of a 100-ft radius zone and tracked their movements for 10-h periods using harmonic radar and tested whether host vegetation staged around the perimeter or food availability before release altered movement patterns. Three larvae moved over 300 ft in 10 h, but 93% of larvae moved 100 ft in radius, <4% of larvae reached the center. This percentage decreased as zone size increased. Implications of these results for the regulatory practices of the gypsy moth quarantine are discussed.
Equilibrium Effects of Superstition in the Housing Market

We investigate the interaction of product quality differentiation and consumer preference heterogeneity in durable goods markets, focusing on the effects of secondary market liquidity and consumer heterogeneity on equilibrium prices. We build an infinite-horizon dynamic model of the apartments housing market that captures the above features. Some apartments are considered lucky, and some consumers are superstitious. Lucky apartments are valued more highly than non-lucky ones only by superstitious consumers. Results show that the difference between the lucky apartment price and the non-lucky apartment price becomes smaller when the secondary market becomes less liquid and when consumers’ preference heterogeneity becomes more persistent as opposed to time-varying.
Past or present spirituality? Predicting mental health outcomes in older adults

Although the relationship between current religion/spirituality (R/S) and health outcomes is well-established, we know very little about the extent to which R/S experiences across a lifetime affect...
Gravitational waves from Population III binary black holes formed by dynamical capture

We use cosmological hydrodynamic simulations to study the gravitational wave (GW) signals from high-redshift binary black holes (BBHs) formed by dynamical capture (ex-situ formation channel). We in particular focus on BHs originating from the first generation of massive, metal-poor, so-called Population~III (Pop~III) stars. An alternative (in-situ) formation pathway arises in Pop~III binary stars, whose GW signature has been intensively studied. In our optimistic model, we predict a local GW event rate density for ex-situ BBHs (formed at z>4) of ~0.04 /(yr Gpc^3). This is comparable to or even higher than the conservative predictions of the rate density for in-situ BBHs ~0.01-0.1 /(yr Gpc^3), indicating that the ex-situ formation channel may be as important as the in-situ one for producing GW events. We also evaluate the detectability of our simulated GW events for selected planned GW instruments, such as the Einstein Telescope (ET). For instance, we find the all-sky detection rate with signal-to-noise ratios above 10 to be <100 per year for the xylophone configuration of ET. However, our results are highly sensitive to the sub-grid models for BBH identification and evolution, such that the GW event efficiency (rate) is reduced by a factor of 4 (20) in the pessimistic case. The ex-situ channel of Pop III BBHs deserves further investigation with better modeling of the environments around Pop III-seeded BHs.
Symmetry-preserving WENO-type reconstruction schemes in Lagrangian hydrodynamics

Abstract WENO (Weighted essentially non-oscillatory)-type reconstruction schemes are used to work as a limiter that preserves cylindrical symmetry for radial shock flows on an equal-angle polar mesh in Lagrangian hydrodynamics. These WENO-type limiters are tested with a high-order Lagrangian discontinuous Galerkin (DG) hydrodynamic method. In order to guarantee the compactness of the underlying DG methods, for strong shock problems, canonical WENO and Hermite WENO reconstructions are used for second-order DG(P1) and third-order DG(P2) respectively, using the known DG solution for the target cell as the central stencil. A salient feature of Hermite WENO lies in taking advantage of available information, namely the derivatives that are evolved with the DG method. With a local orthonormal basis or a local characteristic decomposition, the WENO-type reconstruction schemes can guarantee the cylindrical symmetry for Lagrangian hydrodynamics. A suite of challenging test problems are calculated to demonstrate the accuracy and robustness of these WENO-type schemes.
Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis

Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.
TRPM channels mediate learned pathogen avoidance following intestinal distention

Upon exposure to harmful microorganisms, hosts engage in protective molecular and behavioral immune responses, both of which are ultimately regulated by the nervous system. Using the nematode Caenorhabditis elegans, we show that ingestion of Enterococcus faecalis leads to a fast pathogen avoidance behavior that results in aversive learning. We have identified multiple sensory mechanisms involved in the regulation of avoidance of E. faecalis. The G-protein coupled receptor NPR-1-dependent oxygen-sensing pathway opposes this avoidance behavior, while an ASE neuron-dependent pathway and an AWB and AWC neuron-dependent pathway are directly required for avoidance. Colonization of the anterior part of the intestine by E. faecalis leads to AWB and AWC mediated olfactory aversive learning. Finally, two transient receptor potential melastatin (TRPM) channels, GON-2 and GTL-2, mediate this newly described rapid pathogen avoidance. These results suggest a mechanism by which TRPM channels may sense the intestinal distension caused by bacterial colonization to elicit pathogen avoidance and aversive learning by detecting changes in host physiology.
A Simple Reward-free Approach to Constrained Reinforcement Learning.

In constrained reinforcement learning (RL), a learning agent seeks to not only optimize the overall reward but also satisfy the additional safety, diversity, or budget constraints. Consequently, existing constrained RL solutions require several new algorithmic ingredients that are notably different from standard RL. On the other hand, reward-free RL is independently developed in the unconstrained literature, which learns the transition dynamics without using the reward information, and thus naturally capable of addressing RL with multiple objectives under the common dynamics. This paper bridges reward-free RL and constrained RL. Particularly, we propose a simple meta-algorithm such that given any reward-free RL oracle, the approachability and constrained RL problems can be directly solved with negligible overheads in sample complexity. Utilizing the existing reward-free RL solvers, our framework provides sharp sample complexity results for constrained RL in the tabular MDP setting, matching the best existing results up to a factor of horizon dependence; our framework directly extends to a setting of tabular two-player Markov games, and gives a new result for constrained RL with linear function approximation.
DNA Double-strand Break Signaling Is a Therapeutic Target in Head and Neck Cancer.

BACKGROUND Head and neck cancer (HNC) is common worldwide. Given poor outcomes for patients with HNC, research into targeted therapies is needed. Ataxia telangiectasia mutated (ATM) is a DNA damage kinase which is activated by double-strand DNA breaks. We tested the effects of a novel ATM inhibitor on HNC cell lines and xenografts. MATERIALS AND METHODS p53-Binding protein 1 and phosphorylated ATM were localized in cultured cells by immunofluorescence microscopy. Protein expression was determined by western blot. Tumor xenografts were established by injecting HNC lines into immunocompromised mice. Tumor sections were characterized by immunohistochemistry. Apoptotic cells were determined by terminal transferase-mediated dUTP nick-end labeling assay. RESULTS ATM inhibition increased double-strand DNA breaks at replication foci in HNC cell lines. ATM inhibition affected cell-cycle regulatory protein expression, blocked cell-cycle progression at the G2/M phase and resulted in apoptosis. CONCLUSION ATM inhibition may be therapeutically useful in treating HNC.
How to Talk About Sentencing Policy--and Not Disparity

I had difficulty deciding what to speak about in this keynote address. First, I want to talk about why I don’t want to discuss sentencing disparity, why this is an issue far, far less important than issues of sentencing fairness, of proportionality, of what works to address crime. Disparity-speak has sucked the air out of all interesting and meaningful discussion of criminal justice reform for the past several decades. Second, I want to recount one case that dramatizes why the debate on sentencing disparity is beside the point, why we need to talk about real problems of real offenders. Now, of course, sentencing disparity is important even though I don’t want to talk about it. We tell the same disparity stories over and over again. The chair of the United States Sentencing Commission, a very distinguished judge, spoke to my Harvard Comparative Sentencing class this past week, recounting the usual narrative.1 During the Vietnam War era, federal judges were obliged to sentence convicted draft
Fixed prey cue preferences among Dusky Pigmy Rattlesnakes (Sistrurus miliarius barbouri) raised on different long-term diets

Chemoreception is often crucial to the interaction between predators and their prey. Investigating the mechanisms controlling predator chemical preference gives insight into how selection molds traits directly involved in ecological interactions between species. In snakes, prey cue preferences are influenced by both direct genetic control and experience-based plasticity. We assessed prey preference in a group of Dusky Pigmy Rattlesnakes that had eaten only mice or lizards over a 5 year period to test whether genetics or plasticity primarily determine the preference phenotype. Our results provide evidence for genetic determination of preference for lizard chemical cues in pigmy rattlesnakes. Snakes preferred the scent of lizards, regardless of their initial diet, and the response to mouse scent did not differ from the water-only control. We discuss these findings in light of previous studies that manipulated snake diets over shorter timescales.
Biopsychosocial predictors of pain among women recovering from surgery for endometrial cancer.

Abstract Objective This study investigated post-surgical changes in pain among endometrial cancer patients, as well as the extent to which emotional distress and inflammatory and regulatory cytokine levels were associated with pain. Methods Women ( N =71) who underwent surgery for endometrial cancer completed questionnaires assessing pain intensity and interference, depression, and anxiety at 1week, 4weeks, and 16weeks post-surgery. Participants also provided a blood sample for the analysis of a panel of 7 cytokines at the same time points. Results Participants showed significant declines in pain intensity and pain interference from 1week to 4weeks post-surgery, after which pain remained stable. After adjusting for time since surgery, surgery type, adjuvant therapy, disease stage, age, and BMI, mixed-effects linear regression models indicated that greater depression and anxiety were associated with both greater pain intensity and interference. Higher levels of circulating IL-6 were also correlated with greater pain intensity, but not interference. Fixed-effects linear regression models indicated that temporal variation in depression, anxiety, and IL-6 within individual patients was associated with corresponding changes in pain. Pain symptoms were maximal when anxiety, depression, and IL-6 were highest. No other cytokines were associated with changes in pain. Conclusion These findings indicate that depression, anxiety, and IL-6 may exacerbate pain during the recovery period following surgery for a gynecologic malignancy. Targeting these psychological processes and the proinflammatory cytokine IL-6 in women with more severe and persistent pain may help to reduce suffering and improve post-surgical recovery.
Dynamically Controlling Node-Level Parallelism in Hadoop

Hadoop is a widely used large scale data processing framework. Applications run in Hadoop as containers, the concurrency of which affects completion time of an application as well as system resource usage. When there are too many concurrent containers, resource bottlenecks occur and when there too few, system resources are underutilized. The default and best practice settings underutilize resources which results in longer application completion times. In this work, we develop an approach to dynamically change the parallelism for concurrent containers to suit an application. Our approach ensures efficient utilization of resources and avoids bottlenecks for all types of MapReduce applications. Our approach improves performance of MapReduce applications by as much as 28% and 60% respectively when compared to the best practice and default settings.
LBO Financial Model

In leveraged buyout (LBO) financial model, transactions are typically companies in mature industries that have stable and growing cash flow that can be used to service large debt obligations and, potentially, pay dividends to the financial buyers. In addition, targets usually have low capital expenditures, low leverage, and assets that can be sold. Management of the target company will be asked to grow the company's market share and improve margins, creating growth in free cash flow. An LBO analysis includes cash flow projections, terminal value projections (the price at which a financial buyer thinks the company can be sold in 3 to 7 years), present value determination (the price that a financial buyer will pay for a company today), and the analysis solves for the IRR of the investment (the discount rate applied). LBO models require an assumption of a minimum IRR required by financial buyers, based on risks associated with the investment and market conditions. The model solves for the purchase price that creates this targeted IRR. Basically, the LBO analysis answers the question: What is the highest purchase price that can be paid for a company in order to earn a compound annual rate of return that meets the investor's risk-adjusted return requirement? The LBO analysis considers whether there is enough projected cash flow to operate the company and also pay debt principal and interest payments. In addition, the analysis determines if there is sufficient cash flow to pay dividends at some point to the private equity investor. An ability to retire debt and pay dividends results in a higher IRR.
Electrophysiology Tool Construction

This protocol documents the construction of a custom microscope stage system currently in widespread use by a wide variety of investigators. The current design and construction of this stage is the result of multiple iterations, integrating input from a number of electrophysiologists working with a variety of preparations. Thus, this tool is a generally applicable solution, suitable for a wide array of end-user requirements; its flexible design facilitates rapid and easy configuration, making it useful for multi-user microscopes, as individual researchers can reconfigure the stage system or have their own readily replaceable stage plates. Furthermore, the stage can be manufactured using equipment typically found in small research machine shops, and by keeping the various parts on hand, machinists can quickly satisfy new requests and/or modifications for a wide variety of applications.
Modeling methodology for elastomer dynamics

As engineering applications of elastomers increase in complexity, knowledge of the behavior of these materials, and the ability to predict these behaviors, becomes increasingly valuable. Elastomers exhibit a complex variety of mechanical properties, including nonlinear constitutive laws, strong damping and hysteresis (loss of kinetic and potential energy, respectively), and the dependence of strain on its history. Most current models for rubber-like materials assume a form of the strain energy function (SEF), such as a cubic Mooney-Rivlin form or an Ogden form. While these methods can produce good results, they are only applicable to static behavior, and they ignore hysteresis and damping. We discuss a dynamic partial differential equation (PDE) formulation based on large deformation theory elasticity as an alternative approach to the SEF formulation. Models using the PDE formulation are presented for both simple extension and generalized simple shear.
The Schr\"odinger equation and its generalized analogs derived by the quantum hydrodynamic representation

The derivation of the Schrodinger-like equations from the system of equations of the quantum hydrodynamic analogy (QHA) is analyzed in presence of fluctuations. If in absence of fluctuation each QHA solution can be tracked back to the equivalent one of the Schrodinger problem, in presence of fluctuations the work shows that the ensemble of solution of the QHA equations is wider than the Schrodinger one and the tracking-back procedure from the QHA problem to the original Schrodinger equation is not generally possible. The break-down of the mathematical correspondence is inspected and correlated to the characteristics of the states. Finally, the paper shows that if the form of Schrodinger equation is generalized, the QHA stochastic case as well as its classical limit can be translated into a Schrodinger-like representation.
The Potential of High‐throughput Metagenomic Sequencing of Aquatic Bacterial Communities to Estimate the Postmortem Submersion Interval

Human remains can be discovered in freshwater or marine ecosystems, circumstances where insects and other invertebrates have infrequently been used for understanding the time of postmortem submersion. In this study, the identification and succession of epinecrotic bacterial communities on vertebrate remains were described during decomposition in a temperate headwater stream during two seasons (summer and winter). Bacterial communities were characterized with 454 pyrosequencing and analyzed at phyletic and generic taxonomic resolutions. There was a significant increase in genera richness over decomposition during both seasons. Additionally, multivariate statistical modeling revealed significant differences in bacterial communities between seasons at both taxonomic resolutions and siginificant genera differences among sampling days within each season, suggesting a succession of these communities. These data are the first to describe aquatic bacterial succession using high-throughput metagenomic sequencing on vertebrate remains submerged in a freshwater habitat, and provide initial evidence for their potential use in forensic investigations.
A Variational Level Set Approach to Segmentation and Bias Correction of Images with Intensity Inhomogeneity

This paper presents a variational level set approach to joint segmentation and bias correction of images with intensity inhomogeneity. Our method is based on an observation that intensities in a relatively small local region are separable, despite of the inseparability of the intensities in the whole image caused by the intensity inhomogeneity. We first define a weighted K-means clustering objective function for image intensities in a neighborhood around each point, with the cluster centers having a multiplicative factor that estimates the bias within the neighborhood. The objective function is then integrated over the entire domain and incorporated into a variational level set formulation. The energy minimization is performed via a level set evolution process. Our method is able to estimate bias of quite general profiles. Moreover, it is robust to initialization, and therefore allows automatic applications. The proposed method has been used for images of various modalities with promising results.
S-Nitrosylation at the Interface of Autophagy and Disease

In this issue of Molecular Cell, Sarkar et al. (2011) provide the first evidence for involvement of nitric oxide bioactivity in autophagy and suggest new insight into the role of aberrant S-nitrosylation in the pathogenesis of neurodegeneration.
Forbearance in leadership: Opportunities and risks involved in cutting followers some slack

Abstract The concept of forbearance in leadership is introduced as an explanation for certain managerial behavior which, despite a superficial appearance of mere leniency, plays an important role in preserving the social fabric of the workplace. A conceptual grounding based on Social Exchange Theory and the managerial stewardship literature is presented, and four categories of forbearance are identified. To apply the concept, the conclusions of an important series of articles on performance appraisal are reconsidered in forbearance terms, rather than from their original political deviance perspective. Opportunities and risks associated with practicing forbearance are described, and theoretical assertions in the form of research propositions are offered.
Relationship between cardiac protein tyrosine phosphorylation and myofibrillogenesis during axolotl heart development.

Abstract The axolotl, Ambystoma mexicanum , is a useful system for studying embryogenesis and cardiogenesis. To understand the role of protein tyrosine phosphorylation during heart development in normal and cardiac mutant axolotl embryonic hearts, we have investigated the state of protein tyrosine residues (phosphotyrosine, P-Tyr) and the relationship between P-Tyr and the development of organized sarcomeric myofibrils by using confocal microscopy, two-dimensional isoelectric focusing (IEF)/SDS-polyacrylamide gel electrophoresis (PAGE) and immunoblotting analyses. Western blot analyses of normal embryonic hearts indicate that several proteins were significantly tyrosine phosphorylated after the initial heartbeat stage (stage 35). Mutant hearts at stages 40–41 showed less tyrosine phosphorylated staining as compared to the normal group. Two-dimensional gel electrophoresis revealed that most of the proteins from mutant hearts had a lower content of phosphorylated amino acids. Confocal microscopy of stage 35 normal hearts using phosphotyrosine monoclonal antibodies demonstrated that P-Tyr staining gradually increased being localized primarily at cell–cell boundaries and cell–extracellular matrix boundaries. In contrast, mutant embryonic hearts showed a marked decrease in the level of P-Tyr staining, especially at sites of cell–cell and cell–matrix junctions. We also delivered an anti-phosphotyrosine antibody (PY 20) into normal hearts by using a liposome-mediated delivery method, which resulted in a disruption of the existing cardiac myofibrils and reduced heartbeat rates. Our results suggest that protein tyrosine phosphorylation is critical during myofibrillogenesis and embryonic heart development in axolotls.
NASA Advanced Refrigerator/Freezer Technology Development Project Overview

NASA Lewis Research Center (LeRC) has recently initiated a three-year project to develop the advanced refrigerator/freezer (R/F) technologies needed to support future life and biomedical sciences space experiments. Refrigerator/freezer laboratory equipment, most of which needs to be developed, is enabling to about 75% of the planned space station life and biomedical sciences experiments. These experiments will require five different classes of equipment: three storage freezers operating at −20°C, −70°C and ≤183°C, a −70°C freeze-dryer, and a cryogenic (≤183°C) quick/snap freezer. This project is in response to a survey of cooling system technologies, performed by a team of NASA scientists and engineers. The team found that the technologies, required for future R/F systems to support life and biomedical sciences spaceflight experiments, do not exist at an adequate state of development and concluded that a program to develop the advanced R/F technologies is needed. Limitations on spaceflight system size, mass, and power consumption present a significant challenge in developing these systems. This paper presents some background and a description of the Advanced R/F Technology Development Project, project approach and schedule, general description of the R/F systems, and a review of the major R/F equipment requirements.
Statistical hazard detection using shadows for small robotic landers/hoppers

Small robotic vehicles are limited in mass and computational resources. To enable future missions, new methods that provide hazard detection while reducing the mass and computational load from complex sensors and algorithms will provide cost effective solutions for safe landing. This paper describes a technique for hazard detection using shadows and statistical methods to determine the most likely safe landing aim point during traverse and approach to landing at a new surface location. The number and size of shadows is used to statistically determine the safest locations. This method assumes that higher density of shadows infers greater roughness, and larger shadows infer larger hazards. This simpler statistical shadowing hazard detection technique can be used to enable smaller lander/hopper missions which are restricted in their sensor payloads and which traverse across a planet's surface at low altitudes. This allows hazard detection to begin at large distances and shallow path angles. The low computational resources needed for this technique enables constant reassessment of potential landing sites during the duration of traverse from one location to another. This paper presents analysis showing the performance of this method under varying approach angles. The method for hazard detection is compared to techniques proposed for conventional landers. We discuss how this method can be used for hopper missions.
The impact of standards-based reform: applying Brantlinger's critique of 'hierarchical ideologies'

Brantlinger's [2004b. “Ideologies Discerned, Values Determined: Getting past the Hierarchies of Special Education.” In Ideology and the Politics of (in)Exclusion, edited by L. Ware, 11–31. New York...
Data Selection in Semi-supervised Learning for Name Tagging

We present two semi-supervised learning techniques to improve a state-of-the-art multi-lingual name tagger. For English and Chinese, the overall system obtains 1.7% - 2.1% improvement in F-measure, representing a 13.5% -- 17.4% relative reduction in the spurious, missing, and incorrect tags. We also conclude that simply relying upon large corpora is not in itself sufficient: we must pay attention to unlabeled data selection too. We describe effective measures to automatically select documents and sentences.