cssi/SciSciGPT-SciSciNet huggingface dataset:
The science pendulum: From programmatic to incremental-and back?

The climate in which scientific research is conducted changes over time, and in recent years there has been a shift from a positive view of programmatic science to a more negative evaluation that its contribution to scientific progress is only incremental. In this special issue focusing on the tools of a programmatic approach—replication, reliability and reproducibility—I reflect on changes in scientific practice over my research career, considering some factors contributing to changes in emphasis and highlighting potential pitfalls, particularly in terms of the impact on scientific progress and future scientists. In concluding, I suggest that, as members of the scientific community, we can influence current scientific practices in our day-to-day roles as authors, reviewers, investigators, editors, employers, and educators.
Innovative New Apps and Uses for the Accounting Classroom

ABSTRACT: New instructional technologies provide educators with opportunities for student engagement and collaboration. As technology evolves, educators will spend more time identifying and testing new platforms. This instructional resource paper reviews several recent innovative technologies by providing brief descriptions, pricing, and current and potential uses. More specifically, this paper examines Doceri and DisplayNote in detail. My results from analyzing exam scores and course grades identified that the use of Doceri improves overall course performance in an introductory managerial accounting class. Poll Everywhere is an audience response system using mobile phones, Twitter, and the web in place of clickers. Student surveys suggest that the use of the Poll Everywhere app encourages questions and class discussions. Students perceived they participated more, and the class provided more illustrative examples with the utilization of the Poll Everywhere app. Top Hat is a cloud-based classroom and stude...
Linkage Mapping and Comparative Genomics of Red Drum (Sciaenops ocellatus) Using Next-Generation Sequencing

Developments in next-generation sequencing allow genotyping of thousands of genetic markers across hundreds of individuals in a cost-effective manner. Because of this, it is now possible to rapidly produce dense genetic linkage maps for nonmodel species. Here, we report a dense genetic linkage map for red drum, a marine fish species of considerable economic importance in the southeastern United States and elsewhere. We used a prior microsatellite-based linkage map as a framework and incorporated 1794 haplotyped contigs derived from high-throughput, reduced representation DNA sequencing to produce a linkage map containing 1794 haplotyped restriction-site associated DNA (RAD) contigs, 437 anonymous microsatellites, and 44 expressed sequence-tag-linked microsatellites (EST-SSRs). A total of 274 candidate genes, identified from transcripts from a preliminary hydrocarbon exposure study, were localized to specific chromosomes, using a shared synteny approach. The linkage map will be a useful resource for red drum commercial and restoration aquaculture, and for better understanding and managing populations of red drum in the wild.
Feline urine metabolomic signature: characterization of low-molecular-weight substances in urine from domestic cats.

ObjectivesThis aim of this study was to characterize the composition and content of the feline urine metabolome.MethodsEight healthy domestic cats were acclimated at least 10 days before starting t...
Palliative efficacy and local control of conventional radiotherapy for lung metastases.

Background: The lung is a common site of metastasis, and conventionally fractionated radiotherapy (CFRT) is commonly used to treat such metastases, usually to palliate symptoms. However, no data exists to quantify palliation or local control (LC) of CFRT for secondary lung tumors. We aimed to describe the palliative effect of CFRT for lung metastases at our institution, and compare its LC with that of stereotactic body radiation therapy (SBRT). Methods: 182 patients received 190 courses of RT for lung metastases (99 CFRT, 91 SBRT). We characterized the proportion of CFRT patients who experienced palliation, the durability of palliative effect, and cumulative incidence of local failure (LF) using competing-risks regression. We also performed an exploratory comparison of LF between CFRT and SBRT. Results: In CFRT patients, cumulative incidence of LF at 6 months and 1 year was 32% and 43%, respectively. Rate of initial palliation was 74%. Palliation rates for the most common indications were as follows: hemoptysis 86% (25/29), cough 71% (12/17), airway obstruction 66% (25/38), pain 64% (7/11). Of patients who reported palliation, 6-month and 1-year cumulative incidence of symptom recurrence was 52% and 65%, respectively. In SBRT patients, LF at 6 months and 1 year was 5.8% and 19.5%, respectively. Conclusions: CFRT effectively alleviates a variety of symptoms in lung metastases, supporting its continued use in palliation of metastatic disease. However, subsequent local progression and symptom relapse are common with CFRT. As SBRT is associated with higher rates of LC, this may be preferred in eligible patients with more favorable prognosis.
Abstract 105: Racial Differences in Health Status, Clinical Characteristics and Treatment Patterns Among Patients With Peripheral Artery Disease: Insights From the PORTRAIT Registry

Background: Despite the higher prevalence and excess morbidity associated with peripheral arterial disease (PAD) in blacks, as compared with whites, little is known about racial differences in clin...
BHP Billiton Group: Long-Term Debt (a)

BHP Billiton Group issued two tranches of long-term debt in March 2009. Details and terms of those debt issues are provided. The case can be used to illustrate the accounting for long-term debt and publicly traded corporate bonds. Excerpt UVA-C-2317 Rev. Oct. 24, 2011 BHP Billiton Group: Long-Term Debt (A) The historically low interest rate environment characterizing the years 2008–10 led many international companies to tap the world's corporate bond markets. Companies large and small, investment grade and junk, were rushing to strengthen their balance sheets and lock in attractive rates. Worldwide corporate bond sales in 2009 totaled a record $ 3 trillion. Yields on 10-year U.S. Treasuries had fallen below 3.5%, approximately half the yields of a decade earlier, and were trending lower (Exhibit 1). The BHP Billiton Group (BHP), headquartered in Melbourne, Australia, was one of the many companies to issue new debt in 2009 under these favorable debt-market conditions. BHP Billiton Group BHP was the world's largest natural-resources company, and its many diversified businesses produced aluminum, copper, coal, iron ore, gold, lead, silver, and diamonds. Its operations spanned the globe, with the heaviest concentration in Asia and Europe (Exhibit 2). The company had an employee and contractor base spread across more than 25 countries totaling almost 100,000. Revenues exceeded $ 50 billion, and its market capitalization approximated $ 144 billion. . . .
Size and Seasonal Change in Dimensions

Temperatures in the bodies of birds and mammals are specifically established and regulated to within a few degrees. Heat is produced by metabolism that, except in hibernation, does not normally fall below a basal level. As temperature of the environment changes, the various components of overall insulation vary the escape of metabolic heat in a manner that regulates the body temperature. Basal metabolic rates are related to size and they show no relation to climates. One component of overall insulation, the fur, is limited in thickness by the short stature of the small mammals, and the overall insulation of these small mammals is correspondingly limited. Among arctic mammals the size of a fox (Alopex lagopus), greater than 4 kg), fur and overall insulation suffice to maintain normal body temperature in any arctic weather.
Hermeneutic Modes, Ancient and Modern

The history of philosophy is first of all a matter of interpreting texts. But texts, as we know, can be interpreted in a variety of ways. Whoever studies or teaches or writes the history of philosophy uses some interpretive mode, and a first philosophic problem for the history of philosophy is to determine the number and nature of interpretive modes. Since we like to call the art of interpretation hermeneutics, we may call this the problem of hermeneutic modes. This is the problem that we will here address.
Immunologic Approach to Therapy in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progresssive neurodegenerative disorder of aging characterized clinically by the loss of memory (especially of recent events), intellect and cognitive functions. The etiology and the pathogenesis of AD is unknown, and there is no effective treatment available. However, some good hypotheses are presently being investigated (see ref. #1–3). These include speculations that AD is caused by: (a) an infectious agent, perhaps a virus; (b) abnormal function of immune system or immunoincompetence; (c) genetic predisposition as in ‘familial’ AD; (d) disturbance of brain biochemistry (neurotransmitters, neuropeptides and/or neurotropic factors); and (e) exposure to toxic substances like aluminum. Current immune studies have shown abnormalities of both cell-mediated and humoral immunity, supporting an immune hypothesis in the pathogenesis of AD or at least in a subset of immune origin (4–6), especially since clinical as well as genetic heterogeneity (7) exists among patients presented with this disease. One possible immune mechanism may involve autoimmunity perhaps secondary to a virus infection (i.e. a humoral immune response to body’s own constituents, specifically brain antigens in the case of AD). Relevant of this hypothesis is a recent observation which showed a temporal link of a unconventional virus infection in AD; this was shown based upon the transmissibility of Creutzfeldt-Jacob disease (CJD)-like histopathology in the hamsters inoculated intracerebrally with buffy coat cells (white blood cells) of the blood from AD patients (8). This paper describes the rationale for the development of therapy with immunomodulating agents.
Arctic sea ice thickness, volume, and multiyear ice coverage: Losses and coupled variability (1958-2018)

Large-scale changes in Arctic sea ice thickness, volume and multiyear sea ice (MYI) coverage with available measurements from submarine sonars, satellite altimeters (ICESat and CryoSat-2), and satellite scatterometers are summarized. The submarine record spans the period between 1958 and 2000, the satellite altimeter records between 2003 and 2018, and the scatterometer records between 1999 and 2017. Regional changes in ice thickness (since 1958) and within the data release area of the Arctic Ocean, previously reported by Kwok and Rothrock (2009 Geophys. Res. Lett. 36 L15501), have been updated to include the 8 years of CryoSat-2 (CS-2) retrievals. Between the pre-1990 submarine period (1958–1976) and the CS-2 period (2011–2018) the average thickness near the end of the melt season, in six regions, decreased by 2.0 m or some 66% over six decades. Within the data release area (~38% of the Arctic Ocean) of submarine ice draft, the thinning of ~1.75 m in winter since 1980 (maximum thickness of 3.64 m in the regression analysis) has not changed significantly; the mean thickness over the CS-2 period is ~2 m. The 15 year satellite record depicts losses in sea ice volume at 2870 km3/decade and 5130 km3/decade in winter (February–March) and fall (October–November), respectively: more moderate trends compared to the sharp decreases over the ICESat period, where the losses were weighted by record-setting melt in 2007. Over the scatterometer record (1999–2017), the Arctic has lost more than 2 × 106 km2 of MYI—a decrease of more than 50%; MYI now covers less than one-third of the Arctic Ocean. Independent MYI coverage and volume records co-vary in time, the MYI area anomalies explain ~85% of the variance in the anomalies in Arctic sea ice volume. If losses of MYI continue, Arctic thickness/volume will be controlled by seasonal ice, suggesting that the thickness/volume trends will be more moderate (as seen here) but more sensitive to climate forcing.
Understanding Molecular Testing in Patients Affected by Hematologic Disorders

The rapid development of molecular testing has transformed diagnostic approaches to hematologic disorders. Morphologic examination and complete blood counts still have a fundamental role to overall indicate the nature of the hematologic disorder; however, molecular testing now serves in a pivotal role in the clinical care of patients with hematologic malignancies, hemoglobinopathies, and congenital hematological disorders for precise diagnosis. Over the last several decades, laboratory diagnostic approaches have grown to be more rapid, sensitive, and accurate to enable a quicker and more complete diagnosis. In this chapter, we review the basis of these new nucleotide-based molecular techniques and their application in hematologic disorders.
Light-Harvesting in Porous Crystalline Compositions: Where We Stand toward Robust Metal–Organic Frameworks

Molecular assemblies in metal–organic frameworks (MOFs) have the potential to be considered as functional artificial light-harvesting (LH) system with features similar to the natural LH machinery. ...
Knee extensor torque and BMI differently relate to sit-to-stand strategies in obesity.

Abstract Background Obesity alters whole body kinematics during activities of daily living such as sit-to-stand (STS), but the relative contributions of excess body mass and decreased relative strength are unknown. Methods Three-dimensional motion analysis data was collected on 18 obese subjects performing sit-to-stand (chair height: 52 cm). Isometric knee extensor strength was measured at 900 knee flexion. Forward stepwise linear regression was used to determine the association between the independent variables BMI and the knee extensor torque with the dependent variables: foot position and trunk kinematics. Findings BMI, but not knee extensor torque, was inversely related to shank angle and positively related to stance width. Relative knee extensor torque, but not BMI, was inversely associated with initial trunk angle, peak trunk flexion angle, and peak trunk extension velocity (r2 = 0.470–0.495). BMI was positively associated with peak trunk flexion velocity, but no other parameters of trunk kinematics. In the final regression model, BMI was the primary predictor (r2 = 0.423) and relative knee extensor strength served as a secondary predictor (r2 = 0.118) of peak trunk flexion velocity. Interpretation BMI and knee extensor strength differently contribute to sit-to-stand performance strategies in obese subjects. Muscle strength may be an important determinant of whole-body kinematics during activities of daily living such as STS.
Statistical outbreak detection by joining medical records and pathogen similarity.

Abstract We present a statistical inference model for the detection and characterization of outbreaks of hospital associated infection. The approach combines patient exposures, determined from electronic medical records, and pathogen similarity, determined by whole-genome sequencing, to simultaneously identify probable outbreaks and their root-causes. We show how our model can be used to target isolates for whole-genome sequencing, improving outbreak detection and characterization even without comprehensive sequencing. Additionally, we demonstrate how to learn model parameters from reference data of known outbreaks. We demonstrate model performance using semi-synthetic experiments.
Modeling the Factors of User Success in Online Debate

Debate is a process that gives individuals the opportunity to express, and to be exposed to, diverging viewpoints on controversial issues; and the existence of online debating platforms makes it easier for individuals to participate in debates and obtain feedback on their debating skills. But understanding the factors that contribute to a user's success in debate is complicated: while success depends, in part, on the characteristics of the language they employ, it is also important to account for the degree to which their beliefs and personal traits are compatible with that of the audience. Friendships and previous interactions among users on the platform may further influence success. In this work, we aim to better understand the mechanisms behind success in online debates. In particular, we study the relative effects of debaters' language, their prior beliefs and personal traits, and their social interactions with other users. We find, perhaps surprisingly, that characteristics of users' social interactions play the most important role in determining their success in debates although the best predictive performance is achieved by combining social interaction features with features that encode information on language use during the debate.
Over 100-THz bandwidth selective difference frequency generation at LaAlO3/SrTiO3 nanojunctions.

The ability to combine continuously tunable narrow-band terahertz (THz) generation that can access both the far-infrared and mid-infrared regimes with nanometer-scale spatial resolution is highly promising for identifying underlying light-matter interactions and realizing selective control of rotational or vibrational resonances in nanoparticles or molecules. Here, we report selective difference frequency generation with over 100 THz bandwidth via femtosecond optical pulse shaping. The THz emission is generated at nanoscale junctions at the interface of LaAlO3/SrTiO3 (LAO/STO) that is defined by conductive atomic force microscope lithography, with the potential to perform THz spectroscopy on individual nanoparticles or molecules. Numerical simulation of the time-domain signal facilitates the identification of components that contribute to the THz generation. This ultra-wide-bandwidth tunable nanoscale coherent THz source transforms the LAO/STO interface into a promising platform for integrated lab-on-chip optoelectronic devices with various functionalities. A nanojunction structure developed by researchers in the US can generate tunable terahertz radiation over a wide bandwidth. Terahertz radiation, occupying the upper end of microwave and lower end of infrared, causes atoms and molecules to resonate, revealing useful information about the physical structure of matter. However, terahertz radiation is difficult to generate. Lu Chen and co-workers in Jeremy Levy’s group at the University of Pittsburgh used an atomic force microscope to create nano-sized junctions between lanthanum aluminate and strontium titanate. By shining two frequencies of laser light onto a voltage-biased nanojunction, they could produce radiation at the difference of the two frequencies as high as 100 terahertz. Because the nanojunction can both generate and detect terahertz radiation, it could be used to manipulate and observe nanoscale objects such as quantum dots or individual molecules.
Research on the structures and application scenarios of medium voltage AC-DC hybrid distribution network

AC-DC hybrid distribution network refers to the distribution network with AC-DC conversion power electronic devices such as converters and inverters. Compared with the traditional AC distribution network, AC-DC hybrid distribution network is more suitable to connect high penetration DGs and DC loads. This paper summarized the advantages and typical structures of medium voltage AC-DC hybrid distribution network along with their characteristics, then the application scenarios of medium voltage AC-DC distribution network are categorized and their suitable structures are analyzed.
Finding a minimum feedback arc set in reducible flow graphs

Abstract We present a polynomial-time algorithm for finding a minimum weight feedback arc set (FAS) in arc-weighted reducible flow graphs and for finding a minimum weight feedback vertex set (FVS) in vertex-weighted reducible flow graphs. The algorithm has time complexity O(mn 2 log ( n 2 m )) , where n is the number of vertices and m is the number of arcs in the reducible flow graph. For unweighted reducible flow graphs, the algorithm for FAS has time complexity O( min (mn 5 3 , m 2 )) . We also show that any algorithm that solves the FAS problem or the vertex-weighted FVS problem on reducible flow graphs has time complexity at least that of finding a minimum cut in a flow network, for which the best algorithm currently known has time complexity Θ(mn log ( n 2 m )) for networks with arbitrary capacities, and Θ( min (mn 2 3 , m 3 2 )) for networks with unit capacities. Our results establish several connections between the FAS problem on reducible flow graphs and the minimum cut-maximum flow problem on flow networks.
Near- (2020) and long-term (2030–2035) costs of automated, electrified, and shared mobility in the United States

Abstract Revolutions in shared mobility services, vehicle electrification, and automated vehicle technology will affect urban traffic patterns, energy use and CO2 emissions, the automotive industry, public transportation, and more. This paper examines the monetary costs of these innovations for users in the near-term (approximately 2020) and how they may evolve in the long-term (approximately 2030–2035). We estimate traveler costs for light duty vehicle trips on a per-mile basis, and investigate their sensitivity to vehicle powertrain, vehicle size, travel mode and intensity of vehicle use, and DC charging assumptions. To highlight differences between human and automated driving, we consider only autonomous vehicle scenarios in the long-term. We document three main findings. First, as battery costs continue to drop over the next decade, private battery electric vehicles will become more cost-competitive with internal combustion vehicles; and in high-mileage ridesourcing applications, electric vehicles will be much more cost-competitive. Second, near-term ridesourcing trips will likely remain about 4–5 times the per-mile cost of driving one's own car, while pooled trips cut this factor to around 3. Third, in the long-term automated vehicles may make ridesourcing cheaper than driving one's own vehicle. Even if the manufacturing cost of automated vehicles remains high, this cost will be minor when amortized over a service life of 400,000 miles. These findings are unchanged even with significant variations in assumed future battery and automation costs, electricity (charging) cost, vehicle insurance and maintenance cost, and ridesourcing providers' overhead rates.
Nonpharmacological Treatment of Army Service Members with Chronic Pain Is Associated with Fewer Adverse Outcomes After Transition to the Veterans Health Administration.

Potential protective effects of nonpharmacological treatments (NPT) against long-term pain-related adverse outcomes have not been examined. To compare active duty U.S. Army service members with chronic pain who did/did not receive NPT in the Military Health System (MHS) and describe the association between receiving NPT and adverse outcomes after transitioning to the Veterans Health Administration (VHA). A longitudinal cohort study of active duty Army service members whose MHS healthcare records indicated presence of chronic pain after an index deployment to Iraq or Afghanistan in the years 2008–2014 (N = 142,539). Propensity score-weighted multivariable Cox proportional hazard models tested for differences in adverse outcomes between the NPT group and No-NPT group. NPT received in the MHS included acupuncture/dry needling, biofeedback, chiropractic care, massage, exercise therapy, cold laser therapy, osteopathic spinal manipulation, transcutaneous electrical nerve stimulation and other electrical manipulation, ultrasonography, superficial heat treatment, traction, and lumbar supports. Primary outcomes were propensity score-weighted proportional hazards for the following adverse outcomes: (a) diagnoses of alcohol and/or drug disorders; (b) poisoning with opioids, related narcotics, barbiturates, or sedatives; (c) suicide ideation; and (d) self-inflicted injuries including suicide attempts. Outcomes were determined based on ICD-9 and ICD-10 diagnoses recorded in VHA healthcare records from the start of utilization until fiscal year 2018. The propensity score-weighted proportional hazards for the NPT group compared to the No-NPT group were 0.92 (95% CI 0.90–0.94, P < 0.001) for alcohol and/or drug use disorders; 0.65 (95% CI 0.51–0.83, P < 0.001) for accidental poisoning with opioids, related narcotics, barbiturates, or sedatives; 0.88 (95% CI 0.84–0.91, P < 0.001) for suicide ideation; and 0.83 (95% CI 0.77–0.90, P < 0.001) for self-inflicted injuries including suicide attempts. NPT provided in the MHS to service members with chronic pain may reduce risk of long-term adverse outcomes.
Net flux of glucose, lactate, volatile fatty acids, and nitrogen metabolites across the portal-drained viscera and liver of pregnant ewes.

Our objective for this study was to determine the pattern of nutrient flux across the portal-drained viscera (PDV) and liver in ewes with varying numbers of fetuses. Catheters were placed in the hepatic portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta of ewes. Blood flow and net nutrient release across the PDV and liver were determined before exposure to rams. Ewes were then mated, which resulted in two ewes not pregnant and in six ewes with single and 11 ewes with twin lambs. Additional measurements were taken 103, 82, 61, 39, 19, and 6 d before parturition. Net PDV glucose release did not differ from zero (-.4 +/- 8.4 mmol/h; P = .58). In ewes with singles, premating net hepatic glucose release was 34.4 +/- 2.4 mmol/h, and 19 d before parturition it was 46.2 +/- 3.8 mmol/h. In ewes with twins, premating net hepatic glucose release was 36.8 +/- 2.7 mmol/h, and 19 d before parturition it was 47.4 +/- 2.8 mmol/h. Net PDV lactate release did not differ with litter size (P = .58) or days from parturition (P = .14; 9.7 +/- 4.6 mmol/h). Net lactate uptake by the liver increased in pregnant ewes as the pregnancy progressed (P < .001). The hepatic extraction ratio for lactate increased in late pregnancy (P = .02). Net PDV and hepatic release of acetate and propionate were not different with litter size or days from parturition. Hepatic extraction ratios of VFA did not differ with litter size or day from parturition. The patterns of change in hepatic metabolite fluxes are similar to the patterns of change in gravid uterus metabolite uptake. Hepatic lactate uptake seems to be regulated during pregnancy.
On becoming a doctoral student: Chinese doctoral students’ socialization of capital and habitus in academia

This study examines Chinese international doctoral students’ academic socialization into TESOL discourses and communities. Rooted in the academic discourse socialization theory, complemented by the...
Stereophonic Frequency Modulation using MATLAB: An Undergraduate Research Project

Frequency modulation (FM) is used worldwide for high-fidelity broadcast radio communication. This paper presents a MATLAB implementation of a stereophonic FM transmitter and receiver. Simulations are performed to measure the performance of the stereophonic FM receiver in the presence of additive white Gaussian noise (AWGN). A stereophonic FM signal with pre-detection SNR values from 0 to 60 dB, in increments of 10 dB, is demodulated using a discriminator. Post-detection SNR values are determined, and performance characteristics are examined for above and below threshold modes of FM operation. The simulations show that the receiver reliably demodulates the message signal for pre-detection SNR values greater than 30 dB. Degradation of the signal occurs at and below 20 dB with a complete loss of signal at 0 dB (below threshold mode). A 15 dB post-detection SNR gain occurs at 60 dB pre-detection SNR.
Adaptive Modulation Regenerator and Distance Aware Algorithm for Dynamic Routing in Elastic Optical Networks

The Elastic Optical Network is a technology that offers versatile conversion of modulation format, allowing for more effective use of spectrum resources compared to the traditional fixed grid in WDM networks. Additionally, the content-oriented services offered by geographically distributed data centres raise a need for cost-effective and scalable data delivery. In this paper, we discuss Routing, Modulation and Spectrum Allocation (RMSA) in content-oriented networks, based on the Elastic Optical Network. We propose a new adaptive modulation, regenerator and distance-aware algorithm. Our findings discover an interesting trade-off between the request blocking and regenerator use.
Should I Stay or Leave?: Exploring the Relationship between Reverse Transfer and Degree Attainment

This research aims to explore the relationship between reverse transfer and degree attainment by addressing the following questions: 1) What are the predictors of reverse transfer? 2) Does reverse ...
LIGHTNING TALK: Creating Higher Order Assignments In Art-Writing Intensive Courses

Session LOCATION: George's (3rd Floor of the Johnson Center) For this study, I looked at syllabi and assignment sheets from art-writing intensive courses collected by the Writing Across the Curriculum Department at George Mason University in order to discover how they ask students to think about their writing goals. Using Bloomâs Taxonomy to evaluate the language used to describe courses and writing assigned, I determined most writing-intensive courses are utilizing the higher levels of Bloomâs Taxonomy, requiring rigorous assignments and addressing high order concerns.
Brain-selective mTOR inhibitors as potential therapeutics for glioblastoma multiforme

4485 Glioblastoma multiforme (GBM) is one of the most common primary CNS tumors and remains essentially universally fatal despite aggressive therapy. Many GBM cells have loss of PTEN function which confers increased activity of PI3K/Akt pathway. This in turn activates the mTOR, thereby increasing translation of a number of key proteins required for cell cycle progression. PTEN-deficiency in GBM has been associated with the poor prognosis of the disease. Inhibition of mTOR resulting in cell cycle arrest and apoptosis is therefore a rational approach for the development of novel anticancer therapeutics for this devastating disease. Three analogues of rapamycin, CCI-779, RAD001 and AP23573 are currently in clinical trials as potential anticancer agents. These rapamycin analogues are structurally very close to rapamycin with only a single ester or ether substitution at the C40 hydroxyl, and thus share many biological similarities to rapamycin, including some poor metabolic stability and pharmacokinetic drawbacks. A recent publication of CCI-779 Phase II study in patients with recurrent GBM suggests the agent is not effective, probably due to its poor penetration into the central nervous system (CNS) ( Investigational New Drugs 23, 357–361, 2005). We report here a series of novel rapamycin analogues generated by genetically engineered biosynthesis with significantly improved pharmaceutical properties as well as potent anticancer activities. Among this structurally diverse set of rapamycin analogues, we have identified compounds that have up to 4-fold increased water solubility, >100-fold increased Caco-2 permeability, 30-fold reduced efflux ratio and significantly increased metabolic stability over rapamycin. For example, BC210 has low nanomolar inhibitory potency against mTOR and exhibits potent anticancer activities in various in vitro and in vivo assays. It is not a substrate of P-gp and has a good oral bioavailability. Of particular importance is the effective penetration of the blood-brain barrier by BC210. When given i.v. 3 mg/kg in mice, it ‘accumulates’ in the brain resulting in the brain to blood ratio of 1.6 which is unique among all known rapamycin analogues. This unique pharmacokinetic property of BC210 makes the compound a highly promising candidate as a potential therapeutic for the treatment of GBM, either alone or in combination with other anticancer therapeutics. Structure-activity relationship, pharmacological characterisation and in vivo evaluation in an orthotopic in vivo GBM model of this series of novel mTOR inhibitors will be discussed.
Cyclosporin A in der Dermatologie

Die klassischen Immunsuppressiva Glukokortikosteroide und Azathioprin hemmen die Zellteilung aller Elemente des Immunsystems sowie die Produktion von Zytokinen. Das ist ein relativ breit gefachertes Spektrum von Wirkungen. Im Gegensatz dazu inhibiert Cyclosporin A (CsA) selektiv die adaptative Immunantwort, vorrangig den T-Zellschenkel, bis zu einem gewissen Grade aber auch davon unabhangig den B-Zellschenkel. Daneben verursacht es dosisabhangig eine Reihe von nicht-immunologischen Nebenwirkungen, deren genaue Kenntnis Voraussetzung fur den therapeutischen Einsatz dieses auserordentlich interessanten Medikaments ist.
Recreation Expenditures and Opportunity Theory: The Case of Illinois.

With the exception of measures reflecting travel distance, travel time, or travel cost, the literature devoted to the understanding and prediction of the economic impact of recreation has oversimplified the characterization of the spatial or locational aspects of the distribution of opportunities facing decision makers. In this paper, the relative effects of site characteristics are compared to the spatial context within which recreators make destination choices in accounting for variations in per person per day expenditures. The results show that for a large portion of Illinois households the agglomerative effects and contextual effects of spatial structure are the principal factors influencing per person per day expenditure levels.
Self-perceived competence and social acceptance of children who stutter

Abstract Purpose This study examined self-perceived general competence and social acceptance in young children who stutter (CWS) as compared to children who do not stutter (CWNS), and assessed the extent to which temperament, speech disfluency, language abilities, and home environment both co-vary and predict children's perception of their own competence. Methods Data were collected from 16 CWS and 16 CWNS between the ages of 4; 0 and 5;10. Standardized assessments of perceived competence and social acceptance, temperament, expressive language, receptive language, and home environment were collected from each child, as well as stuttering severity ratings for the CWS. Results Results indicated that CWS and CWNS did not significantly differ in self-perceived general competence or perceived social acceptance. Regression analyses revealed that for CWS and CWNS combined a) surgency and negative affectivity best predicted perceived competence, and (b) negative affectivity and receptive language best predicted perceived social acceptance. For CWS only, stuttering severity was added to the analysis and results revealed that (c) surgency and expressive language best predicted perceived competence, and (d) stuttering severity and receptive language best predicted perceived social acceptance. Results approached significance. Conclusions These findings propose that children's speech and language skills seem to be linked to their perception of peer acceptance, while a tendency for risk taking and a generally positive view of new situations may play an important role for self-perception of overall competence in the world. Further, the results implicate a “normal” self-perception on behalf of the CWS in this study, which mirrors the tendency for young children to view themselves in an overly positive light. This inflated sense of ability may serve as a “buffer” between the child's life events (e.g., stuttering) and social-emotional development. Therefore, determining a child's degree of self-perceived competence could be an important contributing factor to a successful therapeutic outcome.
Investigation of Li-Ion Capacitors’ Cycle Performance

Li-ion capacitors were assembled with an activated carbon cathode and hard carbon/stabilized lithium metal powder (SLMP) anode. The stabilities of cathode and anode were determined by different methods, including the half-cell and full-cell methods. It was found that the highest potential of the activated carbon electrode should be less than 4.5 V vs. Li/Li+ potential; while the lowest potential of hard carbon/SLMP electrode should be greater than 0.1 V vs. Li/Li+ potential. Scanning electron microscopy images showed that the growth rate of the solid electrolyte interface (SEI) layer increased rapidly when the lowest potential of hard carbon/SLMP electrode was less than 0.1 V vs. Li/Li+ potential.
Accelerated lifetime and reliability testing of large-deflection piezoelectric microsystems

This paper reports, for the first time, accelerated lifetime testing and reliability of large displacement piezoelectric micro-electromechanical systems (MEMS) over trillions of cycles. Electrical, mechanical, and piezoelectric properties of cantilevers have been monitored over time and the surface topology has been observed through scanning electron microscopy.
A RULE-BASED PROCESS MODEL FOR COOPERATIVE SOFTWARE PROJECTS. TAILORING AND TESTING A SOFTWARE PROCESS TO BE USED ON THE WEB

Abstract In order to support mediated and coordinated web-based software processes the features for software process tailoring and testing are complemented by basic support functions for cooperative teamwork. Rule-based software process modelling is used to define, tailor and test software processes. The resulting model provides a complete and consistent network of activities, artefacts, roles, agents, and resources. Basic features for artefact sharing, agent notification or activity control are adopted for software team coordination.
Impugning alleged randomness

According to a 1985 issue of New York Times, “The New Jersey Supreme Court today caught up with the Essex County Clerk and a Democrat who has conducted drawings for decades that have given Democrats the top ballot line in the county 40 times out of 41 times.” But the clerk wasn't punished. Here's another case of that sort, from Israel. In the 1980s the Israeli tax authorities encouraged the public to request invoices from plumbers, painters, etc. and send the invoices in; big prices were ruffled off. It turned out that the winner was none other than the Director of Customs and VAT at the time. The operation collapsed but the director wasn't punished. You may be convinced that such lotteries are rigged, but how would you argue that in the court of law? Yes, the probability of the suspicious outcome is negligible. However the probability of any particular outcome is negligible. What can you say? We attempt to furnish you with an argument.
Factor Determinants of Credit Default Swap Spreads

I examine the theoretical determinants for US and European credit default swap spreads. In contrast to previous results, I find that interest rates play a smaller role in determining spreads, and that other equity factors, such as momentum and the Fama-French small-minus-big factor play substantial roles in determining credit default swap spreads. I also allow for coefficients to change over time and find that determinants of credit default swaps spreads change significantly as the volatility of swap spreads rise. Interest rates are found to be significant determinants of the underlying volatility of swap spreads.
Sphingosine Kinase 2 Inhibition and Blood Sphingosine 1-Phosphate Levels

Sphingosine 1-phosphate (S1P) levels are significantly higher in blood and lymph than in tissues. This S1P concentration difference is necessary for proper lymphocyte egress from secondary lymphoid tissue and to maintain endothelial barrier integrity. Studies with mice lacking either sphingosine kinase (SphK) type 1 and 2 indicate that these enzymes are the sole biosynthetic source of S1P, but they play different roles in setting S1P blood levels. We have developed a set of drug-like SphK inhibitors, with differing selectivity for the two isoforms of this enzyme. Although all SphK inhibitors tested decrease S1P when applied to cultured U937 cells, only those inhibitors with a bias for SphK2 drove a substantial increase in blood S1P in mice and this rise was detectable within minutes of administration of the inhibitor. Blood S1P also increased in response to SphK2 inhibitors in rats. Mass-labeled S1P was cleared more slowly after intravenous injection into SphK2 inhibitor-treated mice or mice lacking a functional SphK2 gene; thus, the increased accumulation of S1P in the blood appears to result from the decreased clearance of S1P from the blood. Therefore, SphK2 appears to have a function independent of generating S1P in cells. Our results suggest that differential SphK inhibition with a drug might afford a method to manipulate blood S1P levels in either direction while lowering tissue S1P levels.
“Pop-slide” patterning: rapid fabrication of microstructured PDMS gasket slides for biological applications

We describe a “pop-slide” patterning approach to easily produce thin film microstructures on the surface of glass with varying feature sizes (3 μm to 250 μm) and aspect ratios (0.066–3) within 45 minutes. This low-cost method does not require specialized equipment to produce microstructured gasket layers for sandwich assays and could be readily applied to many biological applications.
Self-Efficacy in Newly-Hired Child Welfare Workers

Child abuse and neglect in the United States resulted in 676,569 reports in 2011 (U.S. Dept. of Health and Human Services, 2012). Workers in this field struggle with low pay, high caseloads, inadequate training and supervision, and risk of violence, all of which contribute to worker burnout and poor worker retention rates. Worker self-efficacy is predictive of worker retention, job performance, and persistence in this difficult field. This paper reports the development of a new measure of self-efficacy from a sample of 395 child welfare workers. Factor analysis revealed two domains of self-efficacy, direct practice and indirect practice, which can be modestly predicted by worker characteristics upon hire and the training program the workers attend. Worker self-efficacy can be used to identify vulnerable workers who may be especially in need of strong supervisory support as well as understand who to target for recruitment. A review of the literature of self-efficacy in child welfare workers is included.
Magnetic resonance imaging of pelvic floor defects in women.

AbstractContemporary fast magnetic resonance imaging techniques allow dynamic evaluation of the entire female pelvic floor with excellent visualization of pelvic organs and muscular and fascial supportive structures in a single noninvasive study that does not expose the patient to ionizing radiation
Clinical and Statistical Correlation of Various Lumbar Pathological Conditions

Current clinical evaluations often rely on static anatomic imaging modalities for diagnosis of mechanical low back pain, which provide anatomic snapshots and a surrogate analysis of a functional disease. Three dimensional in vivo motion is available with the use of digital fluoroscopy, which was used to capture kinematic data of the lumbar spine in order to identify coefficients of motion that may assist the physician in differentiating patient pathology. Forty patients distributed among 4 classes of lumbar degeneration, from healthy to degenerative, underwent CT, MRI, and digital x-ray fluoroscopy. Each patient underwent diagnosis by a neurosurgeon. Fluoroscopy was taken as the patient performed lateral bending (LB), axial rotation (AR) and flexion-extension (FE). Patient specific models were registered with the fluoroscopy images to obtain in vivo kinematic data. Motion coefficients, C(LB), C(AR), C(FE), were calculated as the ratio of in-plane motion to total out-of-plane motion. Range of motion (ROM) was calculated about the axis of motion for each exercise. Inter- and Intra- group statistics were examined for each coefficient and a flexible Bayesian classifier was used to differentiate patients with degeneration. The motion coefficients C(LB) and C(FE) were significantly different (p<0.05) in 4 of 6 group comparisons. In plane motion, ROM(LB), was significantly different in only 1 of 6 group comparisons. The classifier achieved 95% sensitivity and specificity using (C(FE), C(LB), ROM(LB)) as input features, and 40% specificity and 80% sensitivity using ROM variables. The new coefficients were better correlated with patient pathology than ROM measures. The coefficients suggest a relationship between pathology and measured motion which has not been reported previously.
Alpha-adrenergic receptors in liver membranes: delineation with subtype selective radioligands.

Abstract Alpha 1 and alpha 2 adrenergic receptors have previously been demonstrated in rat liver membranes by competition curves of [ 3 H]dihydroergocryptine ([ 3 H]DHE) with the alpha 1 selective antagonist prazosin (B.B. Hoffman, D. Mullikin-Kilpatrick and R.J. Lefkowitz, J. Biol. Chem. 255 :4645–4652, 1980). The present studies have utilized the radioligands [ 3 H]prazosin and [ 3 H]yohimbine to further define alpha receptors in rat liver membranes. [ 3 H]Prazosin was found to label alpha 1 receptors whereas [ 3 H]yohimbine labelled alpha 2 receptors. The proportion of alpha 1 and alpha 2 receptors determined directly with these radioligands (79% and 20% respectively) was in good agreement with the proportions determined previously with [ 3 H]DHE. Guanine nucleotides were found to reduce the affinity of the agonist epinephrine at the alpha 2 sites labelled by [ 3 H]yohimbine but not at the alpha 1 sites labelled by [ 3 H]prazosin. These results have implications for the interpretation of agonist interactions with alpha receptors in liver membranes.
Formation and hardening effects in nanocrystalline TiN alloys prepared by mechanical alloying

Nanocrystalline Ti-N alloys have been prepared by mechanical alloying in a controlled milling atmosphere. X-ray diffraction, differential scanning calorimetry and microhardness measurements were used to investigate the formation, structure, phase transformation, thermal and mechanical properties of nanocrystalline Ti-N alloys. The relationship among solute content, grain size and microhardness has been studied. The reaction between Ti(N) solid solution and TiN may occur at a relatively low temperature, indicating that the as-formed nanocrystalline Ti-N alloys are metastable and in a high energy state. Strong solid solution hardening has been observed for both the as-milled and the annealed nanocrystalline Ti-N alloys.