cssi/SciSciGPT-SciSciNet huggingface dataset:
Clumped isotope constraints on equilibrium carbonate formation and kinetic isotope effects in freezing soils

Abstract The clumped and stable isotope (Δ47, δ18O, and δ13C) composition of pedogenic (soil) carbonates from cold, arid environments may be a valuable paleoclimate archive for climate change-sensitive areas at high latitudes or elevations. However, previous work suggests that the isotopic composition of cold-climate soil carbonates is susceptible to kinetic isotope effects (KIE). To evaluate the conditions under which KIE occur in cold-climate soil carbonates, we examine the Δ47, δ18O, and δ13C composition of soil carbonate pendants from Antarctica (Dry Valleys, 77°S), the High Arctic (Svalbard 79°N), the Chilean and Argentinian Andes, and the Tibetan plateau (3800–4800 m), and compare the results to local climate and water δ18O records. At each site we calculate the expected equilibrium soil carbonate Δ47 and δ18O values and estimate carbonate Δ47 and δ18O anomalies (observed Δ47 or δ18O minus the expected equilibrium Δ47 or δ18O). Additionally, we compare the measured carbonate δ13C to the expected range of equilibrium soil carbonate δ13C values. To provide context for interpreting the Δ47 and δ18O anomalies, the soil carbonate results are compared to results for sub-glacial carbonates from two different sites, which exhibit large Δ47 anomalies (up to −0.29‰). The Antarctic and 4700 masl Chilean Andes samples have negative Δ47 anomalies and positive δ18O anomalies consistent with KIE due to rapid bicarbonate dehydration during cryogenic carbonate formation. In contrast, the lower elevation Chilean Andes, Argentinian Andes, Tibetan Plateau and High Arctic results are consistent with equilibrium, summer carbonate formation. We attribute the differences in Δ47 and δ18O anomalies to variations in inter-cobble matrix grain size and its effects on the effective soil pore space, permeability (hydraulic conductivity), moisture, and bicarbonate dehydration rate. The Antarctic and 4700 masl Chilean Andean soils have coarse-grained matrices that facilitate rapid bicarbonate dehydration. In contrast, the lower elevation Chilean Andes, Argentinian Andes, High Arctic and Tibetan Plateau soils have finer-grained matrices that decrease the soil pore space, soil permeability and CO2 gas flux, promoting equilibrium carbonate formation. The sub-glacial carbonate samples yield highly variable Δ47 and δ18O anomalies, and we propose that the differences between the two glacier sites may be due to variations in local sub-glacial drainage conditions, pCO2, and pH. Our findings suggest that carbonates from soils with coarse-grained matrices may exhibit KIE in cold climates, making them poor paleoclimate proxies. Soils with fine-grained matrices are more likely to yield equilibrium carbonates suitable for paleoclimate reconstructions regardless of climate. Paleosol matrix grain size should therefore be taken into account in the evaluation of carbonate stable and clumped isotope values in paleoclimate studies.
Bending of biomimetic scale covered beams under discrete non-periodic engagement

Abstract Covering elastic substrates with stiff biomimetic scales significantly alters the bending behavior via scales engagement. This engagement is the dominant source of nonlinearity in small deflection regime. As deformation proceeds, an initially linear bending response gives way to progressive stiffening and thereafter a geometrically dictated ‘locked’ configuration. However, investigation of this system has been carried out until date using assumption of periodic engagement even after scales contact. This is true only under the most ideal loading conditions or if the scales are extremely dense akin to a continuum assumption on the scales. However, this is not true for a practical system where scales are more discrete and where loading can alter periodicity of engagement. We address this nonlinear problem for the first time in small deflection and rotation regime. Our combined modeling and numerical analysis show that relaxing periodicity better represents the geometry of discrete scales engagement and mechanics of the beam under general loading conditions and allows us to revisit the nonlinear behavior. We report significant differences from predictions of periodic models in terms of predicting the behavior of scales after engagement. These include the difference in the angular displacement of scales, normal force magnitudes along the length, moment curvature relationship as well as a distinct nature of the locking behavior. Therefore, non-periodicity is an important yet unexplored feature of this problem, which leads to insights, absent in previous investigations. This opens way for developing the structure-property-architecture framework for design and optimization of these topologically leveraged solids.
Mesothelioma Carcinogenesis: In Vivo Models

Knowledge of the factors and mechanisms responsible for cancer induction rests largely on the development of animal models. In these models, both benign and malignant tumors, as well as preneoplastic lesions, can be induced by proper experimental designs and with appropriate controls, and their analogy to human pathology can be determined. The animal models can be used to test and identify agents (chemical, physical, or biologic) that are capable of carcinogenic activity, and to investigate their mechanisms. In addition, species and strains of laboratory animals with specific genetic susceptibility to specific types of spontaneous or induced tumors can be identified. Recently, genetic manipulation has given rise to transgenic or gene-deleted (knockout) animals, which can reveal selective molecular pathways to carcinogenesis. The study of in vivo animal models of carcinogenesis has sometimes followed the indications of the evidence derived from studies of human epidemiology, especially for occupational and environmental carcinogens. On the other hand, with the systematic development of animal bioassays, many experimentally identified active carcinogens have been subsequently shown to be human carcinogens in epidemiologic studies. Bioassays of potential carcinogenic agents in animal models, previously carried out on a smaller scale, became more systematic in the past 40 years, and they provided a basis for public health measures and primary cancer prevention. The choice of animal biossays depends on our knowledge of the underlying mechanisms of carcinogenesis for different classes of carcinogens. For example, knowledge of the biochemical pathways of metabolic activation of many organic carcinogens in human and animal tissues determined the selection of metabolically competent animal models and corresponding modes of administration. In turn, the animal models have provided an indispensable tool for the study of pathogenetic mechanisms of carcinogenesis, and for the investigation of inhibitory factors (chemoprevention).
Triaging Acute Care Patients During a Disaster

The elderly are at increased risk for poor outcomes both during and following disasters. Some of this excess morbidity and mortality can be avoided by public health planning that takes into consideration the unique needs of our aging population. However the scope of some disasters may be such that, demand for resources exceeds supplies. When this happens, resources must be allocated in a legal and ethical way to do the greatest good for the greatest number. Triage policies should be specific, transparent, objective, and explicit. Triage should only be invoked as a last resort when all possible avenues of resource procurement have been exhausted. Prior health status, prognosis, and age may be considered when making triage decisions. To avoid secondary illness or injury, frail individuals who do not require emergency care should be triaged to safe areas where they can receive psychosocial and medical support services until they can be reunited with their families.
Atomic Spectroscopy, Forensic Science Applications

Standard and emerging atomic spectroscopy and mass spectrometry techniques for criminal and nuclear forensic analyses are presented with general figures of merit for each technique. The use of multielement and isotopic fingerprinting for determining associations between samples and characterizing sample origin and history is addressed along with factors influencing measurement uncertainty. Examples of elemental and isotopic analysis are presented for glass, bullet lead, and nuclear material forensics.
Better to overestimate than to underestimate others’ feelings: Asymmetric cost of errors in affective perspective-taking

Abstract Accurately assessing other people’s perspective in general, and other people’s emotional responses in particular, is essential for successful social interaction. However, substantial research finds that accurate perspective taking is the exception rather than the norm. Although errors in perspective taking are common, little is known about their consequences. Is it worse to overestimate or to underestimate other people’s emotional responses? Seven experiments find that underestimating the intensity of other people's emotional responses leads to more negative evaluations than overestimating others’ emotions (Experiments 1–5). These results replicate across emotional valence and across observers and targets and occur because people believe that underestimation is indicative of lower effort and empathy in trying to understand the target. Additional experiments identify moderators of these effects, including stereotypical emotions and socially undesirable emotions (Experiments 6–7). The cost of errors in affective perspective taking is asymmetric, leading to important implications for social coordination.
Use of an Online Diet Goal-Setting Tool: Relationships With Gestational Weight Gain.

Abstract Objectives To describe (1) the use of a diet goal-setting tool in a self-directed online intervention aimed at promoting a healthy lifestyle, and (2) the association of tool use with gestational weight gain (GWG). Design Cross-sectional analysis of data from the intervention group in a randomized effectiveness trial. Setting An urban county in the northeastern US. Participants A total of 898 healthy pregnant women aged 18–35 years with body mass indexes of (BMI) ≥18.5 and Main Outcome Measures Physical, sociodemographic, and psychosocial characteristics; use of tool features; and GWG. Analysis Frequencies, chi-square tests of independence, and regression analysis. Results Use of the online dietary tool was 45.1% completed the assessment, 35.3% set a goal, and 22.6% engaged in self-monitoring. Among women with normal BMI, setting ≥2 goals and engaging in self-monitoring were significantly (P Conclusions and Implications Although online diet goal setting is a potentially effective weight management tool for pregnant women with normal BMI, findings suggest that it may not be for higher-BMI women. Additional research is needed to explain this finding.
Linking regions between helices in bacteriorhodopsin revealed.

ABSTRACT Three-dimensional electron-microscopic structural analysis requires the combination of many different tilted views of the same specimen. The relative difficulty of tilting the sample to high angles >60° without introducing severe distortion due to different focal distances across the specimen entails that the observable range of electron diffraction data is often limited to this range of angles. Thus, it is generally not possible to observe the diffraction maxima that lie within the conical region of reciprocal space around the direction perpendicular to the electron microscope grid. The absence of data in this region leads to a predictable distortion in the object, and for ± 60° tilting makes the resolution essentially twice as bad in the direction perpendicular to the grid as it is for the in-plane image. Constrained density map modification and refinement methods can significantly reduce these effects. A method has been developed, tested on model cases, and applied to the electron-microscopic structure determination of bacteriorhodopsin in order to visualize the location of linking regions between helices. Electron-microscopic structural analysis of bacteriorhodopsin (Henderson and Unwin. 1975 Nature [Lond.] 257:28–32.) showed that the molecule consists of seven rods of density each nearly spanning the lipid bilayer. Owing to the distortion introduced by the missing conical region of reciprocal space data, no density was visible for the polypeptide segments linking the α-helices. Density in the refined maps indicates the location of at least five of the extrahelical segments of the polypeptide. The total number of possible ways of interconnecting the helices is reduced from 7! (5,040) to the five most consistent possibilities without recourse to other considerations. In addition, the density for the helical regions is more uniform and cylindrical throughout their length, and the length of the helices increases from 35 to 45 A, close to the membrane thickness of 49 A obtained for membranes dried in vacuo. Only three of the five structures consistent with the location of observed linkers place the seventh helix, onto which the chromophore can be attached by reduction in the light, at a position consistent with the main peak for deuterated retinal in the structure, as derived from neutron diffraction analysis. Two of these models are also consistent with the possible location of some of the reduced chromophore on helix B, at lys 40/41 after reduction in the dark, as well as lys 216 on helix G.
Know thy star, know thy planet: chemo-kinematically characterizing TESS targets

The Transiting Exoplanet Survey Satellite (TESS) has already begun to discover what will ultimately be thousands of exoplanets around nearby cool bright stars. These potential host stars must be well-understood to accurately characterize exoplanets at the individual and population levels. We present a catalogue of the chemo-kinematic properties of 2,218,434 stars in the TESS Candidate Target List using survey data from Gaia DR2, APOGEE, GALAH, RAVE, LAMOST, and photometrically-derived stellar properties from SkyMapper. We compute kinematic thin disc, thick disc, and halo membership probabilities for these stars and find that though the majority of TESS targets are in the thin disc, 4% of them reside in the thick disc and <1% of them are in the halo. The TESS Objects of Interest in our sample also display similar contributions from the thin disc, thick disc, and halo with a majority of them being in the thin disc. We also explore metallicity and [alpha/Fe] distributions for each Galactic component and show that each cross-matched survey exhibits metallicity and [alpha/Fe] distribution functions that peak from higher to lower metallicity and lower to higher [alpha/Fe] from the thin disc to the halo. This catalogue will be useful to explore planet occurrence rates, among other things, with respect to kinematics, component-membership, metallicity, or [alpha/Fe].
Coaching in undergraduate medical education: a national survey

Background: Evidence to support coaching in medical education has grown over the past decade leading educators to search for resources to aid the development of their own coaching programs. A sample of medical schools in the USA were surveyed to describe coaching programs to assist other institutions in the development and implementation of programs.Methods: Participants representing 32 medical schools attending a coaching conference in October 2018 were surveyed via email regarding their undergraduate medical education (UME) coaching programs. The 19-item instrument contained questions on program demographics, program characteristics, coach characteristics, coach training and coach assessment and program evaluation.Results: The response rate was 100% (32/32 programs). Nearly all respondents had a coaching program (53%, 17/32) or were developing one (44%, 14/32) with the majority being implemented in the past five years (82%, 14/17). Professional identity formation (80%, 20/25), professionalism (76%, 19/25), and academic performance (76%, 19/25) were the most commonly identified programmatic goals. The majority of coaches (64%, 16/25) received between 5-25% full time equivalent effort to support their role. Coaches did not formally assess students in any domain at most programs (84%, 21/25) or directly observe their students clinically (76%, 19/25). The majority of programs had formal coach training (88%, 22/25).Conclusion: These results demonstrate that coaching is being used to improve performance, professionalism, and professional identity formation in UME. This sample of coaching programs informs the discussion of coaching in medical education as educators strive to implement effective coaching programs.
Molecular Interrogation to Crack the Case of O‐GlcNAc

The O-linked β-N-acetylglucosamine (O-GlcNAc) modification, termed O-GlcNAcylation, is an essential and dynamic post-translational modification in cells. O-GlcNAc transferase (OGT) installs this modification on serine and threonine residues, whereas O-GlcNAcase (OGA) hydrolyzes it. O-GlcNAc modifications are found on thousands of intracellular proteins involved in diverse biological processes. Dysregulation of O-GlcNAcylation and O-GlcNAc cycling enzymes has been detected in many diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases. Here, recent advances in the development of molecular tools to investigate OGT and OGA functions and substrate recognition are discussed. New chemical approaches to study O-GlcNAc dynamics and its potential roles in the immune system are also highlighted. It is hoped that this minireview will encourage more research in these areas to advance the understanding of O-GlcNAc in biology and diseases.
Homology-directed repair involves multiple strand invasion cycles in fission yeast

Homology-directed repair of DNA double-strand breaks (DSBs) can be a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely through a preference for synthesis-dependent strand annealing (SDSA). While genetic studies highlight a key role for the RecQ helicase BLM/Rqh1 (in human and S. pombe cells, respectively) in promoting non-crossover repair, how homology-directed repair mechanism choice is orchestrated in time and space is not well understood. Here, we develop a microscopy-based assay in living fission yeast to determine the dynamics and kinetics of an engineered, site-specific interhomologue repair event. We observe highly efficient homology search and homology-directed repair in this system. Surprisingly, we find that the initial distance between the DSB and the donor sequence does not correlate with the duration of repair. Instead, we observe that repair is likely to involve multiple site-specific and Rad51-dependent co-localization events between the DSB and donor sequence, suggesting that efficient interhomologue repair in fission yeast often involves multiple strand invasion events. By contrast, we find that loss of Rqh1 leads to successful repair through a single strand invasion event, suggesting that multiple strand invasion cycles reflect ongoing SDSA. However, failure to repair is also more likely in rqh1Δ cells, which could reflect increased strand invasion at non-homologous sites. This work has implications for the molecular etiology of Bloom syndrome, caused by mutations in BLM and characterized by aberrant sister chromatid crossovers and inefficient repair.
De Buenos Aires a Santa María. La (no) escritura de Juan María Brausen como artificio de construcción y escapatoria

This article analyses the ambiguous process of literary invention carried out by Juan Maria Brausen, Juan Carlos Onetti’s novel The Brief Life (1950) protagonist, to disrupt the space and time dimension of the city he lives in, Buenos Aires, relocating himself to Santa Maria, the city he builds in his imagination as an outcome of the failure in trying to write a film script. The article proves and substantiates the conclusion that Juan Maria Brausen’s subjectivity as a failed writer, which allows him to break the limits between reality and introspective hallucination, consist of the following philosophical principles: i) the platonic methexis; ii) the primary and secondary imagination; iii) the Condition and the Persona, the sensitive drive and the formal drive; iv) the Spirit, the oscillation and the image; v) the will of creation; vi) the ideas as infinite, independent, unceasingly moving, godlike thoughts; and vii) the primeval joy.
Surgical stabilization of rib fractures is associated with improved survival but increased acute respiratory distress syndrome.

Abstract Background How the surgical stabilization of rib fractures after trauma affects the development of acute respiratory distress syndrome and impacts survival has yet to be determined in a large database. We hypothesized that surgical stabilization of rib fractures would not decrease the incidence of acute respiratory distress syndrome. Methods The National Trauma Data Bank was queried for all traumatic rib fractures in 2016. Patients were divided into groups with single rib fractures, multiple rib fractures, and flail chest. Nonoperative therapy was compared with stabilization of rib fractures of 1 to 2 ribs or 3+ ribs. Results There were 114,972 total patients with rib fractures meeting inclusion criteria, with 5,106 (4.4%) having flail chest, 24,726 (21.5%) having single rib fractures, and 85,140 (74.1%) having multiple rib fractures. Those with flail chest (15.9%) were most likely to get rib plating in comparison to multiple rib fractures (0.9%) and single rib fractures (0.2%); P Conclusion The increased risk of acute respiratory distress syndrome should be considered in the preoperative assessment for stabilization of rib fractures.
Atypical Cells in Peritoneal Cleft: A Pitfall in Diagnosis of Colorectal Adenocarcinoma.

Atypical cells in peritoneal clefts are usually either reactive mesothelial cells or pT4 colonic adenocarcinoma in colon specimen removed for primary colon cancer. However, rarely if ever are these...
Semantic standards of external exposome data

An individual's health and conditions are associated with a complex interplay between the individual's genetics and his or her exposures to both internal and external environments. Much attention has been placed on characterizing of the genome in the past; nevertheless, genetics only account for about 10% of an individual's health conditions, while the remaining appears to be determined by environmental factors and gene-environment interactions. To comprehensively understand the causes of diseases and prevent them, environmental exposures, especially the external exposome, need to be systematically explored. However, the heterogeneity of the external exposome data sources (e.g., same exposure variables using different nomenclature in different data sources, or vice versa, two variables have the same or similar name but measure different exposures in reality) increases the difficulty of analyzing and understanding the associations between environmental exposures and health outcomes. To solve the issue, the development of semantic standards using an ontology-driven approach is inevitable because ontologies can (1) provide a unambiguous and consistent understanding of the variables in heterogeneous data sources, and (2) explicitly express and model the context of the variables and relationships between those variables. We conducted a review of existing ontology for the external exposome and found only four relevant ontologies. Further, the four existing ontologies are limited: they (1) often ignored the spatiotemporal characteristics of external exposome data, and (2) were developed in isolation from other conceptual frameworks (e.g., the socioecological model and the social determinants of health). Moving forward, the combination of multi-domain and multi-scale data (i.e., genome, phenome and exposome at different granularity) and different conceptual frameworks is the basis of health outcomes research in the future.
Dynamics of COVID-19 Mortality and Social Determinants of Health: A Spatiotemporal Analysis of Exceedance Probabilities.

ABSTRACT Purpose To determine the association of social factors with Covid-19 mortality and identify high-risk clusters. Methods Data on Covid-19 deaths across 3,108 contiguous U.S. counties from the Johns Hopkins University and social determinants of health (SDoH) data from the County Health Ranking and the Bureau of Labor Statistics were fitted to Bayesian semi-parametric spatiotemporal Negative Binomial models, and 95% credible intervals (CrI) of incidence rate ratios (IRR) were used to assess the associations. Exceedance probabilities were used for detecting clusters. Results As of October 31, 2020, the median mortality rate was 40.05 per 100, 000. The monthly urban mortality rates increased with unemployment (IRRadjusted:1.41, 95% CrI: 1.24, 1.60), percent Black population (IRRadjusted:1.05, 95% CrI: 1.04, 1.07), and residential segregation (IRRadjusted:1.03, 95% CrI: 1.02, 1.04). The rural monthly mortality rates increased with percent female population (IRRadjusted: 1.17, 95% CrI: 1.11, 1.24) and percent Black population (IRRadjusted:1.07 95% CrI:1.06, 1.08). Higher college education rates were associated with decreased mortality rates in rural and urban counties. The dynamics of exceedance probabilities detected the shifts of high-risk clusters from the Northeast to Southern and Midwestern counties. Conclusions Spatiotemporal analyses enabled the inclusion of unobserved latent risk factors and aid in scientifically grounded decision-making at a granular level.
Office, Central, and Ambulatory Blood Pressure for Predicting First Stroke in Older Adults: A Community-Based Cohort Study

Hypertension is the most prevalent modifiable risk factor for stroke. Office blood pressure (BP) measurements may have limitations in defining the impact of hypertension on stroke. Our aim was to compare the stroke risk for office, central, and ambulatory BP measurements in a predominantly older population-based prospective cohort. Participants in the CABL study (Cardiovascular Abnormalities and Brain Lesions; n=816; mean age, 70.8±9.0 years; 39.8% men) underwent applanation tonometry of the radial artery for central BP and 24-hour ambulatory BP monitoring. During a follow-up of 9.6±3.1 years, stroke occurred in 76 participants (9.3%). Among office BP variables, only diastolic BP was associated with stroke in multivariable competing risk model (P=0.016). None of the central BP variables showed a significant association with stroke. Conversely, all ambulatory systolic and diastolic BP variables were significantly associated with stroke after adjustment for clinical confounders (all P<0.005). In an additional multivariable competing risk model including both ambulatory systolic and diastolic BP values obtained at the same time of the day, diastolic BP was more strongly associated with stroke than systolic BP in 24-hour, daytime, and nighttime periods (all P<0.05). Therefore, in a predominantly older population-based cohort, office diastolic BP was weakly associated with incident stroke; no central BP variable was prognostic of stroke. However, all ambulatory systolic and diastolic BP values were significantly associated with stroke in multivariable competing risk analyses. Moreover, ambulatory diastolic BP was a stronger predictor of stroke than ambulatory systolic BP.
Video directly observed therapy for patients receiving office-based buprenorphine - A pilot randomized controlled trial.

Abstract Background We conducted a pilot study to assess feasibility of using video directly-observed therapy (DOT) for patients initiating buprenorphine to evaluate whether it is associated with better opioid use disorder (OUD) outcomes when compared to treatment-as-usual (TAU). Methods Pilot randomized controlled trial of adult patients with OUD initiating buprenorphine treatment (n = 78) at two sites (Seattle, WA and Boston, MA) from January 2019 to May 2020. Intervention was video DOT using a HIPAA-compliant smartphone application to record taking daily buprenorphine. Study smartphones, text reminders to upload a video, and calendar summaries of video DOT adherence were provided. Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days). Results Of 78 enrolled, 20 (26 %) were female; 29 (37 %) non-white; and 31 (40 %) homeless. The mean (standard deviation) percentage of doses confirmed by video was 31 % (34 %). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50 % (95 % CI: 40–63 %) in the intervention arm versus 64 % (95 % CI: 55–74 %) among controls; RR = 0.78 (95 % CI: 0.60–1.02, p = 0.07). Engagement at week 12 was 69 % (95 % CI: 56–86 %) v. 82 % (95 % CI: 71–95 %) in the intervention vs. TAU arms, respectively; RR = 0.84 (95 % CI: 0.65–1.10, p = 0.20). Conclusions The video DOT intervention did not result in improvements in illicit opioid use and treatment engagement compared to TAU. The study was limited by low rates of intervention use. Trial registration ClinicalTrails.gov, NCT03779997 , Registered on December 19, 2018.
Synthesis and biological evaluation of selective survivin inhibitors derived from the MX-106 hydroxyquinoline scaffold.

Abstract The survivin (BIRC5) expression is very low in normal differentiated adult tissues, but it is one of the most widely upregulated genes in tumor cells. The overexpression of survivin in many cancer types has been positively correlated with resistance to chemotherapy, tumor metastasis, and poor patient survival. Survivin is considered to be a cancer specific biomarker and serves as a potential cancer drug target. In this report, we describe the design and syntheses of a series of novel selective survivin inhibitors based on the hydroxyquinoline scaffold from our previously reported lead compound MX-106. The best compound identified in this study is compound 12b. In vitro, 12b inhibited cancer cell proliferation with an average IC50 value of 1.4 μM, using a panel of melanoma, breast, and ovarian cancer cell lines. The metabolic stability of 12b improved over MX-106 by 1.7-fold (88 vs 51 min in human microsomes). Western blot analyses demonstrated that treatments with 12b selectively decreased survivin protein levels, but negligibly affected other closely related members in the IAP family proteins, and strongly induced cancer cell apoptosis. In vivo, compound 12b effectively inhibited melanoma tumor growth when tested using a human A375 melanoma xenograft model. Further evaluation using an aggressive, orthotopic ovarian cancer mouse model showed that 12b was highly efficacious in suppressing both primary tumor growth in ovaries and tumor metastasis to multiple peritoneal organs. Collectively, results in this study strongly suggest that the hydroxyquinoline scaffold, represented by 12b and our earlier lead compound MX-106, has abilities to selectively target survivin and is promising for further preclinical development.
The Challenge of the Future

The presentation will focus primarily on Marketing and Branding Forms organizations and groups who are interested in competing in the future. The seven slides that pertain to the Shuttle program briefly describe the Oribital Processing Facilities and other important facilities, how big the Shuttle is in comparison to a D-9, and engine information. I talk about my role in the program through the Forms Management program and then move into the Marketing and Branding portion.
Actin Doesn’t Do the Locomotion: Secretion Drives Cell Polarization

Cell polarity refers to the asymmetry in cell shape resulting from asymmetrical protein distribution within a cell in order to serve a specialized cell function or directional cell division. Mechanisms of cell polarization are conserved through evolution and are achieved by conserved multiprotein complexes. Recent advances have revealed that protein transport plays a key role in both the mechanisms and the regulation of cell polarity.
RIP: Routing Information Protocol: A Routing Protocol Based on the Distance-Vector Algorithm

This chapter analyzes the performance of the routing information protocol (RIP) model. A router in the network needs to look at the packet's destination address and determines which output port serves as the best choice to get the packet to the address. It is observed that the router makes this decision by consulting a forwarding table. Routing algorithms are required to build the routing tables and hence, forwarding tables. The basic problem of routing is to find the lowest-cost path between any two nodes. Routing is achieved in most practical networks by running routing protocols among the nodes. The protocols provide a distributed, dynamic way to solve the problem of finding the lowest-cost path in the presence of link and node failures and changing edge costs. One of the main classes of routing algorithms is the distance-vector algorithm. Each node constructs a vector containing the distances to all other nodes and distributes that vector to its immediate neighbors. A router also sends an update message whenever a triggered update from another router causes it to change its routing table.
Data and Methods to Facilitate Delivery System Reform: Harnessing Collective Intelligence to Learn from Positive Deviance

Researchers often focus on the data and methods to assess policy changes, but data and methods can also be policy tools. To improve, health care systems need mechanisms and incentives for continually gathering, assessing, and acting on data. This requires (1) more comprehensive data, (2) converting data into information, and (3) incentives to apply that information. Restructured economic incentives can encourage clinicians to increase value (higher quality and/or lower cost) for their patients. While necessary, incentives are not sufficient—information is also needed. Incentives can lead clinicians to demand better information. Much of the necessary data is already used in patient care and billing; some additional variables will come directly from patients. The notion builds on two concepts: collective intelligence and positive deviance. The former characterizes knowledge gained from observing the behavior of many independent actors adapting to changing situations. Positive deviants are those who achieve far better results than expected. By rewarding positive deviants, rather than trying to identify and “correct” those who are problematic, providers will voluntarily identify themselves and their methods for achieving superior outcomes.
Basic CP Theory: Search

Constraint programming (CP) is based on the fundamental idea that the resolution of hard optimization problems is best approached by the combination of a declarative model specification and the writing of a search procedure. The search procedure explores the underlying search space while taking advantage of the pruning derived from the declarative model. The search is a fundamental ingredient to exploit the specificities of problems that are difficult or near impossible to capture through the declarative model. The flexibility it provides lead to marked successes for truly challenging problems in scheduling, bounded program verification, test generation, and distributed systems, to name just a few. This article offers a gentle introduction to search in CP, what it can do, and how it is used. Keywords: constraint programming; optimization; algorithms; search strategy; heuristics
Phosphorus bioavailability in the chick: effects of protein source and calcium level.

Three experiments utilizing 1,104 broiler cockerels were conducted to establish optimum dietary conditions for the determination of phosphorus (P) bioavailability. The reference P source was KH2PO4. A response-surface design and purified diets containing casein as the protein source were utilized in Exp. 1 Various levels of calcium (Ca) and P supported near-maximal gain in tibia ash. Optimal gain in tibia ash was attained at 1.8% Ca and .55% total (highly available) P. Regression equations describing the gain in tibia ash in response to added P from KH2PO4 for diets in Exp. 2 that contained casein and isolated soybean protein had different (P less than .05) slopes. Diets moderately limiting in available P exhibited reduced gain in tibia ash content if more than 1.4% total Ca was present. A corn-soybean meal diet was utilized in Exp. 3. Partitioning of tibia ash gain into effects due to basal diet, added P from KH2PO4, or P from the test ingredient was investigated. Sunflower meals containing 42 or 28% crude protein were evaluated for P bioavailability. The P content of the meals was 21.6 and 22.7% available, respectively. The fiber of the sunflower hull did not interfere with P availability. Selection of diet ingredients is discussed with respect to the development of P bioavailability values for use in practical diets.
Impact and mitigation of ionospheric anomalies on ground‐based augmentation of GNSS

[1] This paper describes the impact that extreme ionospheric spatial gradients occurring during severe ionospheric storms have on Global Navigation Satellite System Ground Based Augmentation Systems and how the U.S. Local Area Augmentation System (LAAS) mitigates the integrity risk due to these events. Gradients in slant ionospheric delay of as large as 425 mm/km over baselines of 40–100 km have been observed in the United States during ionospheric storms since April 2000 by both the U.S. Wide Area Augmentation System and the network of Continuously Operating Reference Stations receivers. Because ionospheric gradients affecting a LAAS site may not be observed by the LAAS Ground Facility (LGF) before users are affected, a simulation-based method has been developed to determine, in near real time, which potential LAAS user geometries would be unacceptably threatened by a hypothetical worst-case ionosphere gradient. Geometries of this type are made unavailable to LAAS users by having the LGF inflate the broadcast ionospheric-gradient sigma, which increases the Vertical Protection Level of the unacceptable geometries so that they exceed the allowed Vertical Alert Limit; thus ensuring user safety.
Rapid free-breathing dynamic contrast-enhanced MRI using motion-resolved compressed sensing

Compressed sensing is a powerful rapid imaging approach for Magnetic Resonance Imaging (MRI) and has been applied to many clinical applications. In this work, we propose a new use of sparsity in addition to speed. In particular, we present a novel way of handling respiratory motion using compressed sensing for dynamic contrast-enhanced MRI. The proposed technique, called XD-GRASP (eXtra-Dimensional Golden-angle RAdial Sparse Parallel MRI), sorts the continuously acquired radial k-space data into undersampled contrast phases at multiple respiratory motion states using the self-navigation properties of radial imaging and employs a multidimensional compressed sensing reconstruction to exploit sparsity along both contrast-enhancement and respiratory motion dimensions. XD-GRASP improves image quality and also enables to track respiratory motion during contrast enhancement, which can potentially be of clinical value.
CHARACTERIZATION OF CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE IV : ROLE IN TRANSCRIPTIONAL REGULATION

We have characterized Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV), expressed using the baculovirus/Sf9 cell system, to assess its potential role in Ca2+-dependent transcriptional regulation. CaM kinase IV was strongly inhibited in vitro by KN-62, a specific CaM kinase inhibitor which suppresses Ca2+-dependent transcription of several genes, so we tested whether CaM kinase IV could stimulate transcription. Co-transfection of COS-1 cells by cDNA for CaM kinase IV gave 3-fold stimulation of a reporter gene expression, whereas co-transfection with CaM kinase II gave no transcriptional stimulation. Since this transcriptional response was mediated by phosphorylation of cAMP responsive element-binding protein (CREB), we determined the kinetics and site specificities of CaM kinases IV and II for phosphorylating CREB in vitro. CaM kinases IV and II and cAMP kinase (protein kinase A) all had similar Km values for CREB (1-5 microns), but the Vmax of CaM kinase IV was 40-fold lower than those of CaM kinase II and protein kinase A. Although all three kinases phosphorylated Ser133 in CREB, CaM kinase II also gave equal phosphorylation of a second site which was not Ser98. The two CREB phosphorylation sites were separately 32P-labeled, and the abilities of protein phosphatases 1, 2A, and 2B (calcineurin) to dephosphorylate them were tested. Our results show that all three phosphatases could dephosphorylate both sites, and calcineurin was a stronger catalyst for dephosphorylating site 1 (Ser133) than for site 2. These results indicate that CaM kinase IV may be important in Ca2+-dependent transcriptional regulation through phosphorylation of Ser133 in CREB. The fact that CaM kinase II phosphorylates another site in addition to Ser133 in CREB raises the possibility that this second phosphorylation site may account for the suppressed phosphorylation site may account for the suppressed ability of CaM kinase II to enhance transcription through the CRE/CREB system. In addition multiple protein phosphatases, including calcineurin, may exert a modulatory effect on transcription depending on which site they dephosphorylate.
NORCAL-WMP: 13 Flight Days on 7 Days, 1978

Thirteen seeding flights on seven days, beginning 11 JAN 1978 released a total of only 1.62 kg of Agl before the Northern California Weather Modification Project (NORCAL-WMP) was suspended on 6 FEB because of heavy rains, and then terminated by its sponsor, the California Department of Water Resources (DWR). This report summarizes a detailed study, flight by flight, of this very limited operation (Court, 1978). Precipitation immediately downwind from the seeding was slightly greater than at surrounding gages, although the actual amounts were too small for any practical significance.
Generic robotic and motion control API based on GISC-Kit technology and CORBA communications

This paper presents a generic robot and motion control applications programmers interface (API) based on generic intelligent systems control (GISC) technology and CORBA communications. The API provides a generic high-level interface for command sequences between a supervisory control system and devices ranging from one degree of freedom motion devices up to six degree of freedom robotic systems. The API manages distributed robotic control using CORBA communications across numerous platforms ranging from Unix workstations to PCs. The paper presents a description of the API functions and classes used to integrate the Sandia-developed GISC control architecture and commercial CORBA software to support device-independent robotic control.
Arbuscular mycorrhizal colonization of semi-aquatic grasses along a wide hydrologic gradient.

The effect of soil flooding on arbuscular-mycorrhizal (AM) fungal colonization of wetland plants was investigated using Panicum hemitomon and Leersia hexandra, two semi-aquatic grasses (Graminaceae) that grow along a wide hydrologic gradient in Carolina bay wetlands of the southeastern US coastal plain. Three related investigations were conducted along the dry-to-wet gradient in these wetlands; a field survey of AM fungal root colonization in eight wetlands, monthly monitoring of colonization patterns in P. hemitomon over a growing season, and an inoculum potential bioassay of soils collected along the gradient. The field survey showed that AM fungal colonization was strongly negatively correlated with water depth, but colonization was present in most root samples. The monthly assessment indicated that AM fungal colonization was lowest in plots that were consistently wet but rose as some plots underwent seasonal drying. The inoculum potential assay of dry, intermediate, and wet soils performed under both dry and saturated conditions showed that soils that were wet for >1 yr had the same ability to form mycorrhizas in bait plants as those that had remained dry. These findings suggested that the lower degree of colonization in wet areas observed in the field survey was because of the presence of surface water rather than low numbers of mycorrhizal propagules in the soil. Overall, the results of these investigations show that flooding is partially but not totally inhibitory to AM fungal colonization of wetland grasses.
Adaptive Multilinear Tensor Product Wavelets

Many foundational visualization techniques including isosurfacing, direct volume rendering and texture mapping rely on piecewise multilinear interpolation over the cells of a mesh. However, there has not been much focus within the visualization community on techniques that efficiently generate and encode globally continuous functions defined by the union of multilinear cells. Wavelets provide a rich context for analyzing and processing complicated datasets. In this paper, we exploit adaptive regular refinement as a means of representing and evaluating functions described by a subset of their nonzero wavelet coefficients. We analyze the dependencies involved in the wavelet transform and describe how to generate and represent the coarsest adaptive mesh with nodal function values such that the inverse wavelet transform is exactly reproduced via simple interpolation (subdivision) over the mesh elements. This allows for an adaptive, sparse representation of the function with on-demand evaluation at any point in the domain. We focus on the popular wavelets formed by tensor products of linear B-splines, resulting in an adaptive, nonconforming but crack-free quadtree (2D) or octree (3D) mesh that allows reproducing globally continuous functions via multilinear interpolation over its cells.
Human Adaptive Evolution at Myostatin (GDF8), a Regulator of Muscle Growth

Myostatin (GDF8) is a negative regulator of muscle growth in mammals, and loss-of-function mutations are associated with increased skeletal-muscle mass in mice, cattle, and humans. Here, we show that positive natural selection has acted on human nucleotide variation at GDF8, since the observed ratio of nonsynonymous:synonymous changes among humans is significantly greater than expected under the neutral model and is strikingly different from patterns observed across mammalian orders. Furthermore, extended haplotypes around GDF8 suggest that two amino acid variants have been subject to recent positive selection. Both mutations are rare among non-Africans yet are at frequencies of up to 31% in sub-Saharan Africans. These signatures of selection at the molecular level suggest that human variation at GDF8 is associated with functional differences.
Global relationship between the proteome and transcriptome of human skeletal muscle

Skeletal muscle is one of the largest tissues in the human body. Changes in mRNA and protein abundance in this tissue are central to a large number of metabolic and other disorders, including, commonly, insulin resistance. Proteomic and microarray analyses are important approaches for gaining insight into the molecular and biochemical basis for normal and pathophysiological conditions. With the use of vastus lateralis muscle obtained from two groups of healthy, nonobese subjects, we performed a detailed comparison of the muscle proteome, obtained by HPLC-ESI-MS/MS, with the muscle transcriptome, obtained using oligonucleotide microarrays. HPLC-ESI-MS/MS analysis identified 507 unique proteins as present in four out of six subjects, while 5193 distinct transcripts were called present by oligonucleotide microarrays from four out of six subjects. The majority of the proteins identified by mass spectrometry also had their corresponding transcripts detected by microarray analysis, although 73 proteins were onl...