cssi/SciSciGPT-SciSciNet huggingface dataset:
Pediatric renal transplantation under tacrolimus-based immunosuppression.

Background. Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6±5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3±14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5±8.8 hr. The mean number of HLA matches and mismatches was 2.8±1.2 and 2.9±1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0±0.2 years. Results. The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1±0.5 mg/dl, and the corresponding calculated creatinine clearance was 88±25 ml/min/1.73 m 2 . A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3±2.0, -1.7±1.0, and +0.36±1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. Conclusions. These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.
Chronic Neurological Sequelae of Acute Trauma to the Spine and Spinal Cord

The acute-flexion or tear-drop fracture-dislocation associated with injuries of the cervical spinal cord warrants special attention. It is characterized by the separation and downward and forward displacement of the anterior inferior margin of the involved vertebral body. The posterior inferior margin of this same vertebral body is displaced posteriorly into the spinal canal. Acute injuries of this type may be associated with the syndrome of damage to the anterior aspect of the cervical cord. This syndrome may be due to either destruction of this portion of the cord or to compression by displaced bone or disc material. If due to compression, this may be relieved by a surgical procedure. In these cases surgical exploration with the patient in traction and section of the dentate ligaments are indicated, if neurological signs are present. Spine fusion should then be performed at the primary operation, or at a secondary procedure. This will prevent See Images in the PDF file instability of the spine, and the fractured cervical vertebrae will heal in good alignment without the formation of a bony bulge posteriorly. Such bulging may cause chronic compresion of the anterior portion of the cervical spinal cord with neurological sequelae. If the tear-drop fracture is present without neurological signs, spine fusion without laminectomy should be performed after spinal re-alignment by cervical traction.
Integration of Safety Risk Factors in BIM for Scaffolding Construction

of US workers in the construction industry work on scaffolding. Of these workers 4,500 are injured and 50 die every year due to scaffold-related accidents. Proper safety management such as scaffolding safety inspections can support the hazard mitigation and prevention. This paper shares the results of a study of the levels of safety risk at each stage of the scaffoldings project life cycle for building a masonry wall and how these risks and related mitigation suggestions can be applied to Building Information Models (BIM). Safety is integrated with 4 dimensional (4D) BIM by linking the scaffoldings safety risks and mitigations with the project schedule. The 4D BIM can be used as a tool for the safety management to monitor and diminish the safety hazards associated with scaffolding work. Four different stages of research were conducted to determine the safety risks and implement them, and the mitigations, into BIM. (1) Determine the activities associated with working on scaffolding. (2) Collect data from industry professionals about the likelihood and severity of safety hazards at each stage of the scaffolding project life cycle. (3) Establish the safety risks using the collected data and a standardized algorithm. (4) Incorporate the safety risks into BIM and provide mitigation recommendations. As a result, the 4D BIM can be used throughout the project planning and construction progress to inform the safety management of activities associated with the scaffolding that have high safety risks and assist safety management in implementing preventative measures according to given mitigation recommendations.
Secure Content Validation

Information dissemination in electronic form has improved drastically over the past few years. New technologies in Web feeds allow the uses to get notified automatically when new contents are available. Tliough the speedy availability of information is a positive trend, there's also the concern about the validity of information. Let us consider a content producer, who creates and publishes an article based on information from confidential sources. When any of these confidential sources becomes invalid, it is imperative that the end-user who relies on the content of the article be informed. As time passes, the article would have reached many who are often non-traceable to be informed. Given this selling, we develop models for ensuring the confidentiality and secrecy of sources, and also allow the end-user to perform certain operations in reasoning about the validity of articles. We present three types of models, and protocols that solve this problem efficiently.
Identifying rare disease variants in the Genetic Analysis Workshop 17 simulated data: a comparison of several statistical approaches

Genome-wide association studies have been successful at identifying common disease variants associated with complex diseases, but the common variants identified have small effect sizes and account for only a small fraction of the estimated heritability for common diseases. Theoretical and empirical studies suggest that rare variants, which are much less frequent in populations and are poorly captured by single-nucleotide polymorphism chips, could play a significant role in complex diseases. Several new statistical methods have been developed for the analysis of rare variants, for example, the combined multivariate and collapsing method, the weighted-sum method and a replication-based method. Here, we apply and compare these methods to the simulated data sets of Genetic Analysis Workshop 17 and thereby explore the contribution of rare variants to disease risk. In addition, we investigate the usefulness of extreme phenotypes in identifying rare risk variants when dealing with quantitative traits. Finally, we perform a pathway analysis and show the importance of the vascular endothelial growth factor pathway in explaining different phenotypes.
Measurements for understanding the behavior of the genetic algorithm in dynamic environments: a case study using the Shaky Ladder Hyperplane-Defined Functions

We describe a set of measures to examine the behavior of the Genetic Algorithm (GA) in dynamic environments. We describe how to use both average and best measures to look at performance, satisficability, robustness, and diversity. We use these measures to examine GA behavior with a recently devised dynamic test suite, the Shaky Ladder Hyperplane-Defined Functions (sl-hdf's). This test suite can generate random problems with similar levels of difficulty and provides a platform allowing systematic controlled observations of the GA in dynamic environments. We examine the results of these measures in two different versions of the sl-hdf's, one static and one regularly-changing. We provide explanations for the observations in these two different environments, and give suggestions as to future work.
Satellite sea surface temperature time series

Global sea surface temperature measurements (SST) have been produced at NOAA since 1982. Daily global SST images have been composited to allow evaluation of the operational products on workstations. Twelve year time series of SST at fixed locations were extracted from these images for monitoring the SST cycles, such as El Nino, which are most evident along the equatorial Pacific. Comparisons of the satellite SST with in situ equatorial Atlas buoy measurements reveal an intermittent bias that can be related to volcanic aerosols and satellite calibration errors. The NOAA-NASA Pathfinder project will improve the accuracy of the satellite SST products by reprocessing the Advanced Very High Resolution Radiometer (AVHRR) data with consistent algorithms and calibration. These improvements will allow the detection of long term global SST trends, provided the continuity of the satellite systems is maintained. >
Teletech Corporation, 2005

In October 2005, the chief financial officer of a telecommunications company must fashion a response to a corporate raider who claims that a major business segment of this company should be sold because it is not earning a satisfactory rate of return. The case recounts the debate within the company over the use of a single hurdle rate to evaluate all segments of the company versus a risk-adjusted hurdle-rate system. The tasks for the student are to resolve the debate, estimate the weighted-average costs of capital (WACC) for Teletechâ¬"s two business segments, and respond to the raider. The case was prepared to serve as part of an introduction to estimating investorsâ¬" required rates of return. It would best follow one or two class sessions introducing techniques for estimating WACC. The numerical calculations required are light, though some of the subtleties about the use of risk-adjusted hurdle rates will require time for the novice to absorb.â¬?
Renal phosphate adaptation in uraemic dogs with a remnant kidney

1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure. 2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions. 3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relative minor role in the adaptation of phosphate excretion. 4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomized, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown. 5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.
Growth and Characterization of Epitaxial PbTiO3Thin Films On Mgo

Epitaxial PbTiO3 thin films have been grown on single-crystal MgO (100) substrates using metalorganic chemical vapor deposition technique. The energy gap was determined from optical absorption data to be Eg= 3,425 eV. Secondary ion mass spectrometry data showed uniform distribution of Pb, Ti and O atoms with no traces of carbon contamination. Atomic force microscopy studies showed different surface morphology for different film growth rates. In-situ X-ray diffraction data indicate that the tetragonal-to-cubic structural phase transition occurs at about 500-520°C. Above 750 °C the films exhibit multi-phase character, the textured PbTiO3 phase co-existing with a polycrystalline Pb2Ti2O6 structure and a possible Mg-containing impurity phase.
Evaluating Rater Accuracy in Rater-Mediated Assessments Using an Unfolding Model

The number of performance assessments continues to increase around the world, and it is important to explore new methods for evaluating the quality of ratings obtained from raters. This study describes an unfolding model for examining rater accuracy. Accuracy is defined as the difference between observed and expert ratings. Dichotomous accuracy ratings (0 = inaccurate, 1 = accurate) are unfolded into three latent categories: inaccurate below expert ratings, accurate ratings, and inaccurate above expert ratings. The hyperbolic cosine model (HCM) is used to examine dichotomous accuracy ratings from a statewide writing assessment. This study suggests that HCM is a promising approach for examining rater accuracy, and that the HCM can provide a useful interpretive framework for evaluating the quality of ratings obtained within the context of rater-mediated assessments.
The Bacteriostatic Action of Skatole on Gramnegative Enteric Bacilli

In another report1 concerning the bacteriostatic action of indole on the Gram-negative enteric bacilli, the effect of this substance on the character of the bacterial flora in the human intestinal tract was discussed briefly. Although the normal concentration of indole in human feces is not sufficient, per se, to inhibit bacterial growth, the possibility that it may exert an effect in combination with skatole and phenols was pointed out. Mitolo2 reported that the vapor from 5 to 10 mgm. of skatole completely inhibited the growth of the colon bacillus, Staphylococcus pyogenes aureus, and B. pyocyaneo, when these bacteria were seeded on the surface of agar. No information is available, however, concerning the concentrations of skatole which are necessary to prevent the growth of various genera and species of bacteria. It would be expected, a priori, that skatole (methyl-indole), because of its methyl group, would have a greater bacteriostatic effect than indole, and thus it might play a more important role in determining the character of the intestinal flora. Accordingly, a study of the bacteriostatic action of skatole on twenty-five species of Gram-negative enteric bacilli was undertaken. The findings form the basis for this report.
The Study and Achievement of the Elective System Base on JSP and OTP

According to the theoretics of elective regulation under the conditions of the credit system,the basic principle of web database and the technique of network security are firstly analyze,and then a systematic expatiation in aspects of the design thought and runnable principle of the elective system base on the network environment and,the average distribution probability arithmetic are makes.Finally a managing system of the common elective on network by the use of virtual shopping cart thought,trouble removal and OTP are further realized.The experimental result illustrates that this system is steady,effective and higher daptability,full compliance actual need.
Analysis and Comparison on 2000 and 2010 Prevalence and Risk Factors of Stroke in Suzhou

OBJECTIVE To explore the changes of risk factors and epidemic characteristic of stroke in Suzhou,and propose relevant measures of prevention and treatment in early stage.METHODS Multistage cluster random sampling was used in 2000 and 2010 year and residents over 35 years old in Suzhou were sampled to investigate the correlative risk factors of stroke.The same survey content and methods was adopted in this study.RESULTS The standardized morbidity rate of stroke in 2010 year increased significantly than 2000among male,female and each age group.But standardized morbidity rate of urban in 2010 reduced while the rate of rural increased significantly than 2000.Male,age,hypertension,drinking,smoking and do not have physical exercise were risk factors of stroke in 2010.CONCLUSION The morbidity rate of stroke in rural increased quickly and should be paid attention.Comprehensive measures should be carried out to prevent and control stroke according to risk factors of stroke in Suzhou.
Diabetes mellitus and vascular disease.

Are the vascular lesions of diabetes due to a hereditary defect or do the biochemical abnormalities of diabetes produce the vascular disease? Although the answer is not known, evidence suggests tha...
The prevalence of admission for sarcoma in the military health system during 2002-2003.

ABSTRACT The etiology of sarcomas is not clear. Environmental exposures have been implicated as potential agents in the development of some sarcomas, but more research is needed. The military health system (MHS) may be able to provide population-based information regarding sarcomas. Discharge diagnoses for bone sarcoma and soft tissue sarcoma were searched within a large administrative database maintained by the U.S. military. There were >200 cases of bone sarcoma and >300 cases of soft tissue sarcoma during the 2-year study period of 2002–2003. The crude prevalence of admission for bone sarcoma within the MHS was 1.2 cases per 100,000 per year. The crude prevalence of admission for soft tissue sarcoma was 1.7 cases per 100,000 per year. These statistics suggest that the MHS may be used to test hypotheses regarding sarcoma epidemiological features, especially for studies that concern military-related exposures. However, nearly 70% of the military beneficiaries who were sarcoma patients were admitted to ci...
Comparative effectiveness of breast MRI and mammography in screening young women with elevated risk of developing breast cancer: a retrospective cohort study

Screening guidelines recommend that women with 20 % or greater lifetime risk of breast cancer undergo annual breast MRI screening to supplement mammography, irrespective of age. In patients less than 40 years, mammography is often avoided due to concerns about radiation and decreased performance. However, prior studies have been limited by large percentages of women above 40 with decreased breast density. Our purpose was to test whether adding mammography to breast MRI screening compared to breast MRI screening alone in women below 40 increases cancer detection rates. After obtaining IRB approval, chart review identified patients aged 25-40 years undergoing breast MR screening (2005-2014). Demographics, risk factors, BI-RADS assessments, background parenchymal enhancement, and mammographic breast tissue density were recorded. Cancer detection rates, short-term follow-up (BIRADS 3), image-guided biopsy (BIRADS 4,5), and PPV1-3 were calculated. 342 breast MRI exams were identified (average age was 33, 37 % were nulliparous, and 64 % had prior benign biopsy), 226 (66 %) of which underwent concurrent mammography. Risk factors included 64 % with breast cancer in first-degree relative(s), 90 % had heterogeneous or extremely dense breast tissue on mammography, and 16 % were BRCA carriers. Four invasive cancers were detected by MRI (11.7 cancers/1000 examinations, 95 % CI 8.3, 15.1). None of these was detected by mammography, and no cancers were independently identified by mammography. Breast MRI screening in high-risk women under 40 yielded elevated cancer detection rates (11.7/1000). The cancer detection rate for mammography was 0 %, suggesting that MRI alone may be useful in screening high-risk women under 40.
Pulmonary Drug Delivery

Publisher Summary In this chapter, a brief outline of the human respiratory system is provided, and mechanisms of drug particle deposition in human lungs, various pulmonary drug delivery (PDD) devices, and analytical methods associated with characterization of aerosols are also reviewed. An attempt has also been made to assess the challenges and opportunities of pulmonary drug delivery. The therapeutic advantages of selective targeting of drugs to the airways and lungs for the treatment of respiratory diseases are enormous, as are those of the emerging field of systemic delivery via the lung. The pulmonary route is one of the preferred drug delivery routes, since it provides a large surface area for rapid absorption provided by terminal bronchioles and alveoli, a thin (0.1–0.2 mm of alveolar epithelium) physical barrier for absorption, promoting rapid uptake into the bloodstream, and minimal extracellular enzyme levels for metabolic breakdown compared with the gastrointestinal tract. Because of the large surface area and rich blood supply, the pulmonary airway enables rapid onset of therapeutic action even with reduced doses compared to the oral and other systemic routes; therefore, systemic side effects are minimal. Current understanding of in vitro and in vivo relationships for PDD products are incomplete and still evolving, but the correlations showed that in vitro data can be used more widely as a means of comparing different inhaler devices during product development. Pulmonary drug formulation and delivery device technologies are advancing very rapidly, as the pharmaceutical industry moves to adopt the potential advantages of the pulmonary route as an alternative to oral and parenteral delivery methods.
Open pore, elastomeric scaffolds through frustrated particle collapse

This article describes a procedure for making open cell porous elastomeric polymer composites with pore volumes from 40 to 68 vol%, particle loadings up to 49 vol%, and high exposed particle surface area to provide opportunities for multifunctionality. The method exploits particle packing limitations to provide the porous structure during solvent extraction from a melt extrudable solvent-loaded polymer gel composite. During the solvent extraction process, the composite contracts, concentrating the particles, which reduces the interparticle spacing until adjacent particles are nearly in contact. Further solvent removal after particle concentration results in polymer fibrillation and void formation. The final porosity of the composites is dependent on the particle packing efficiency with estimated pore volumes ranging from 39 to 43 vol% for spherical particles to 68 vol% for higher aspect ratio particles. In addition, the particles can be dissolved from the scaffold to leave the unfilled porous elastomer, or partially dissolved to generate a core–shell structure with an outer continuous porosity layer void of particulate surrounding a particle laden porous core. While solvent removal from the gel composite is required, the method does not require the use of a blowing agent, phase separation, or a sacrificial particulate porogen to generate an open porous composite. In addition, the solvent minimizes the viscosity rise associated with high particulate loadings to maintain the ability to melt process the material. It is anticipated that this method of generating open pore composites with available particle surface area will provide opportunities for novel catalyst supports, tissue engineering scaffolds, mass transport applications, and mechanically tailorable materials.
Language Brokering and Depressive Symptoms in Mexican-American Adolescents: Parent–Child Alienation and Resilience as Moderators

This study aimed to untangle the mixed effects of language brokering by examining a contextual factor (i.e., parent-child alienation) and a personal attribute (i.e., resilience) that may relate to adolescents' feelings during translating (i.e., sense of burden and efficacy) and that may moderate the association between such feelings and adolescent depressive symptoms. Participants included 557 adolescent language brokers (Mage = 12.96) in Mexican-American families. Results showed that adolescents with a strong sense of alienation from parents or low resilience (a) experienced more burden or less efficacy in translating and (b) were more susceptible to the detrimental effects of feeling a sense of burden and the beneficial effects of experiencing a sense of efficacy, as measured by depressive symptoms.
The librarian is in

Actuellement, le bibliographe d'une bibliotheque universitaire n'a plus pour seules missions de gerer un service de reference, des instructions bibliographiques et la collection de la bibliotheque, il doit egalement etre en constante liaison avec l'ensemble de la faculte. Le travail de liaison et de communication avec la facutle et les etudians est donc primordial car il permet de mettre en place un certain nombre d'activites
Weight distribution of Iwasawa projection

Abstract In the setting of a connected noncompact semisimple Lie group with a finite center, we prove a property of the Iwasawa decomposition, and use it to show that, in Kostant's convexity result [7] , the Iwasawa projection puts almost all its weight near a single vertex of the convex hull. As another application, we will revisit the results of Huang–Tam [10] , [5] on the iteration of group elements under the Cartan and the Iwasawa decompositions.
A Thermal Storage Unit For Low Temperature Cryocoolers

The Air Force has developed a 10K Cryocooler based on a hybrid approach of combining different cooling technologies into a single cryocooler. The Air Force Hybrid 10K Cryocooler combines a Stirling cryocooler as a precooler and a Joule-Thomson cooling stage to create a cryocooler that produces cooling at 10K.
Franciscus Donders: The Management of Anomalies of Refraction

Living from 1818 to 1889, the story of Franciscus Donders covers much of the nineteenth century. It was a time of enormous confusion regarding many aspects of ophthalmology. Thomas Young’s work in the late eighteenth century proving that the lens rounded up in accommodation was ignored and forgotten. Hypermetropia and its relationship to accommodation was unknown prior to the middle of the century when Donders and Helmholtz would finally unravel the mysteries of this complex physiologic science. Refractive error correction with both concave and convex lenses was thought likely to lead to serious and permanent amblyopia. Donders, receiving a classical education, ultimately chose a scientific career path that lead to ophthalmology. His enduring devotion to both the teaching and practice of this medical and surgical subspecialty resulted in the publication, in 1864, of the most practical and in depth textbook of ophthalmologic refractive science of the nineteenth century. This enduring contribution changed the face of ophthalmology forever.
Multiparametric MR imaging of the Prostate: Pitfalls in Interpretation

Multiparametric MR imaging is widely embraced for the diagnosis, staging, and surveillance of prostate cancer. However, normal anatomic structures and many benign entities have overlapping imaging features with prostate cancer. Although some of these entities require biopsy and histopathologic diagnosis, some have characteristic imaging features that are suggestive of their diagnosis. Knowledge of these pitfalls is important in establishing a correct diagnosis and avoiding unnecessary biopsies, as these entities are encountered routinely in clinical practice.
O Perfil dos Novos Devedores nas Organizações da Serra Gaúcha: Um Estudo sobre Inadimplência num Período de Crise Econômica

Estudo realizado na cidade de Caxias do Sul, no estado do Rio Grande do Sul, com o objetivo de tracar um perfil do crescente numero de empresas inadimplentes, no que tange a diversos fatores e caracteristicas apresentados no modelo da pesquisa aplicada, dentro de um mercado regionalmente delimitado, no atual periodo, onde o cenario economico nacional vive uma de suas mais serias crises, de cunho financeiro, de credibilidade e confianca. Alem disso, mostra-se como um importante instrumento na conducao dos negocios para as organizacoes.
Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas.

Resistance to targeted therapies has become increasingly prevalent. We noted that resistance to different targeted therapies occurs by largely common mechanisms. In this study, we used this information for identifying the mechanisms of resistance to enhancer of zeste homolog 2 (EZH2) inhibitors in diffuse large B-cell lymphoma (DLBCL) harboring EZH2 mutations. We discovered that EZH2 inhibitor-resistant DLBCL cells showed activation of the insulin-like growth factor 1 receptor (IGF-1R), MEK, and phosphoinositide-3-kinase (PI3K) pathways. Constitutive activation of IGF-1R, MEK, or PI3K pathways was sufficient to confer resistance to EZH2 inhibitors in DLBCL. The activation of the PI3K/AKT and MAPK pathways decreased TNFSF10 and BAD expression through a FOXO3-dependent mechanism, which was required for the antitumor effects of EZH2i GSK126. We also identified multiple acquired mutations in EZH2 inhibitor-resistant DLBCL cell lines. These mutations independently conferred resistance to EZH2 inhibitors. Mechanistically, cellular thermal shift assays revealed that the acquired EZH2 mutations that confer resistance to EZH2 inhibitors prevent EZH2 inhibitor binding to the EZH2 mutants. Notably, EZH2 inhibitor GSK126- and EPZ-6438–resistant DLBCL cells remained sensitive to the EZH2 inhibitor UNC1999 and embryonic ectoderm development protein inhibitor EED226, which provides an opportunity to treat DLBCLs that are resistant to these drugs. Collectively, our results underpin the importance for developing a unified approach for forestalling drug resistance by prospectively considering lessons learned from the use of different targeted therapeutic agents.
State-Level Renewable Energy Policy Implementation: How and Why Do Stakeholders Participate?

For most of the 20th century, large-scale, utility-owned power plants dominated electricity generation in the United States. Today, however, a growing share of electricity comes from renewable energy sources such as solar and wind energy, which are often small-scale and distributed. In the absence of significant national policies, the Renewable Portfolio Standard has emerged as the key state-level policy governing the deployment and use of renewable energy sources. While renewable energy offers new possibilities for clean energy generation, it also poses new regulatory and governance challenges as a wide range of stakeholders, such as the utilities, regulatory agencies, environmental and consumer advocacy groups, electricity generators, and private citizens, increasingly seek to influence how Renewable Portfolio Standards are implemented. In this study, we ask: how and why do stakeholders participate in decision-making about how these policies are implemented? Given the unique context of renewable energy policy, the long-term and iterative nature of renewable energy policy implementation, and the wide range of actors involved, we look at the suite of participatory opportunities available to stakeholders. We interview stakeholders in two states—Colorado and Nevada—to identify the mechanisms through which stakeholders participate and the incentives (or disincentives) that influence their willingness to do so. We find that, while decision makers in both states use a variety of mechanisms to engage stakeholders in decision-making, meaningful participation may be limited to stakeholder groups that are knowledgeable about the issues, have the resources to engage in long-term and sustained participation, and have long-standing relationships with decision makers and other stakeholders. Although many stakeholders participate in multiple types of processes to achieve a broader range of benefits, they often perceive their participation as superficial; and yet, their continued participation suggests they may play a long game, building coalitions, relationships, and knowledge to position themselves to influence decisions later on. Finally, we find that the regulatory environment influences which participatory processes are available, the incentives for participation, and ultimately the outcomes of stakeholder participation.
Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency

Naive human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is to efficiently revert lineage-primed, conventional human pluripotent stem cells (hPSC) maintained on either feeder-free or feeder-dependent conditions to a naive-like pluripotency with improved functionality. This chemical naive reversion method employs the classical leukemia inhibitory factor (LIF), GSK3β, and MEK/ERK inhibition cocktail (LIF-2i), supplemented with only a tankyrase inhibitor XAV939 (LIF-3i). LIF-3i reverts conventional hPSC to a stable pluripotent state adopting biochemical, transcriptional, and epigenetic features of the human pre-implantation epiblast. This LIF-3i method requires minimal cell culture manipulation and is highly reproducible in a broad repertoire of human embryonic stem cell (hESC) and transgene-free human induced pluripotent stem cell (hiPSC) lines. The LIF-3i method does not require a re-priming step prior to the differentiation; N-hPSC can be differentiated directly with extremely high efficiencies and maintain karyotypic and epigenomic stabilities (including at imprinted loci). To increase the universality of the method, conventional hPSC are first cultured in the LIF-3i cocktail supplemented with two additional small molecules that potentiate protein kinase A (forskolin) and sonic hedgehog (sHH) (purmorphamine) signaling (LIF-5i). This brief LIF-5i adaptation step significantly enhances the initial clonal expansion of conventional hPSC and permits them to be subsequently naive-reverted with LIF-3i alone in bulk quantities, thus obviating the need for picking/subcloning rare N-hPSC colonies later. LIF-5i-stabilized hPSCs are subsequently maintained in LIF-3i alone without the need of anti-apoptotic molecules. Most importantly, LIF-3i reversion markedly improves the functional pluripotency of a broad repertoire of conventional hPSC by decreasing their lineage-primed gene expression and erasing the interline variability of directed differentiation commonly observed amongst independent hPSC lines. Representative characterizations of LIF-3i-reverted N-hPSC are provided, and experimental strategies for functional comparisons of isogenic hPSC in lineage-primed vs. naive-like states are outlined.
Synthesis of graphene oxide membranes on polyester substrate by spray coating for gas separation

Abstract Graphene oxide (GO) membranes have shown promising gas separation characteristics specially for hydrogen showing potential for industrial applications. However, GO membranes made by filtration, the most common synthesis method, contain wrinkles affecting their gas separation characteristics and the method itself is difficult to scale up. In this work, high quality GO membranes are made from GO suspension by easily scalable spray coating technique (and also by filtration method for comparison) on hydrophilic polyester track etch substrates. GO sheet suspensions of large sheet average size (33 µm) and dilute concentrations are used to minimize GO sheet edge-to-edge interactions and minimize extrinsic wrinkle formation. Single gas permeation and separation experiments of equimolar H2/CO2 binary mixture were conducted to evaluate the permeation and separation characteristics of prepared membranes. GO membranes prepared by spray coating offer gas characteristics similar to those made by filtration, however using dilute GO suspension in spray coating reduces the formation of extrinsic wrinkles causing reduction in the porosity of the inter-sheet pathway where the transport of large gas molecules dominates. This study demonstrates an efficient, scalable and cost-effective approach for synthesizing large area GO membranes with enhanced hydrogen separation.
Phase I expansion cohort to evaluate bevacizumab, sorafenib, and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumors.

10519Background: Angiogenesis is required for tumor growth and metastasis. Both VEGF and PDGFR are key regulators of tumor vasculature. In preclinical models, dual inhibition of VEGF and PDGFR sign...
Oligoclonal T Cells Transiently Expand and Express Tim-3 and PD-1 Following Anti-CD19 CAR T Cell Therapy: A Case Report

Clinical trials of chimeric antigen receptor (CAR) T cells in hematologic malignancy associate remissions with two profiles of CAR T cell proliferation kinetics, which differ based upon costimulatory domain. Additional T cell intrinsic factors that influence or predict clinical response remain unclear. To address this gap, we report the case of a 68-year-old woman with refractory/relapsed diffuse large B cell lymphoma (DLBCL), treated with tisagenlecleucel (anti-CD19), with a CD137 costimulatory domain (4-1BB) on an investigational new drug application (#16944). For two months post-infusion, the patient experienced dramatic regression of subcutaneous nodules of DLBCL. Unfortunately, her CAR T exhibited kinetics unassociated with remission, and she died of DLBCL-related sequelae. Serial phenotypic analysis of peripheral blood alongside sequencing of the β-peptide variable region of the T cell receptor (TCRβ) revealed distinct waves of oligoclonal T cell expansion with dynamic expression of immune checkpoint molecules. One week prior to CAR T cell contraction, T cell immunoglobulin mucin domain 3 (Tim-3) and programmed cell death protein 1 (PD-1) exhibited peak expressions on both the CD8 T cell (Tim-3 ≈ 50%; PD-1 ≈ 17%) and CAR T cell subsets (Tim-3 ≈ 78%; PD-1 ≈ 40%). These correlative observations draw attention to Tim-3 and PD-1 signaling pathways in context of CAR T cell exhaustion.
Anisotropic Vapor-Deposited Glasses: Hybrid Organic Solids.

ConspectusThe term “organic solids” encompasses both crystals and glasses. Organic crystals are commonly grown for purification and structure determination and are being extensively explored for applications in organic electronics including field effect transistors. The ability to control the packing of one molecule relative to its neighbors is of critical importance for most uses of organic crystals. Often, anisotropic packing is also highly desirable as it enhances charge transport and optimizes light absorption/emission. When compared to crystals, the local packing in organic glasses is highly disordered and often isotropic. Glasses, however, offer two key advantages with respect to crystals. First, glasses typically lack grain boundaries and thus exhibit better macroscopic homogeneity. Second, glass composition can often be varied over a wide range while maintaining homogeneity. Besides electronic materials, many modern plastics used in a wide range of technologies are organic glasses, and the glassy ...
Left Ventricular Contractility and Wall Stress in Patients With Aortic Stenosis With Preserved or Reduced Ejection Fraction

Abstract Objectives This study sought to determine the prevalence of reduced contractility and uncompensated wall stress in patients with aortic stenosis (AS) with preserved or reduced left ventricular ejection fraction (LVEF) and their impact on survival. Background LVEF in AS is determined not only by contractility but also by loading conditions. Methods Patients with first diagnosis (time 0) of severe AS (aortic valve area, [AVA]≤1 cm2) with prior echo study (-3±1 years) were identified. Contractility was evaluated by plotting midwall fractional shortening (mFS) against circumferential end-systolic wall stress (cESS), stratified by LVEF of 60% at time 0. The temporal changes (from −3 years to time 0) and prognostic value of LVEF, contractility, and wall stress were assessed. Results Of 445 patients, 290 (65%) had LVEF ≥60% (median: 66% [interquartile range {IQR}: 63% to 69%]) and 155 patients (35%) had LVEF Conclusions In patients with severe AS, LVEF
3508 Ciclopirox Olamine Demonstrates Inhibitory Effects on Esophageal Tumor Cells

OBJECTIVES/SPECIFIC AIMS: Drug repositioning has the potential to accelerate translation of novel cancer chemotherapeutics from bench to bedside. The goal of this study was to determine the effects of ciclopirox olamine (CPX) on esophageal tumor cells. METHODS/STUDY POPULATION: We tested the effect of CPX on four esophageal cancer cell lines, assessing cell proliferation and viability by hexosaminidase and clonogenicity assay, respectively. We analyzed the effects of CPX on three-dimensional (3D) esophageal tumor cell spheroids. We also analyzed effects on cell cycle by flow cytometry. For mechanism, we performed western blots for proteins involved in cell cycle regulation, apoptosis and the Wnt/β-catenin pathway. For in vivo effects, we performed a murine xenograft model with intraperitoneal administration of CPX (100 mg/Kg body weight daily). RESULTS/ANTICIPATED RESULTS: CPX inhibited growth of all cell lines in a time and concentration-dependent manner. CPX also inhibited growth of esophageal spheroids. Cell cycle analysis demonstrated G0/G1 arrest in cells treated with CPX. Western blot analyses demonstrated decreased expression of cyclinD1, CDK4, CDK6, and transcriptionally active β-catenin, supporting the role of CPX in cell cycle inhibition and decreased β-catenin activity. Finally, treatment of nude mice with CPX significantly decreased tumor xenograft volume. DISCUSSION/SIGNIFICANCE OF IMPACT: CPX demonstrates anti-tumor properties in esophageal cancer cell lines. The current results justify further research into the mechanism of this inhibition. Additionally, given its established safety in humans, CPX is a potential candidate for repositioning as an adjunct treatment for esophageal cancer.
Age-related differences in brain activations during spatial memory formation in a well-learned virtual Morris water maze (vMWM) task

The current study applied a rodent-based virtual Morris water maze (vMWM) protocol to an investigation of differences in search performance and brain activations between young and older male human adults. All participants completed in-lab practice and testing before performing the task in the fMRI scanner. Behavioral performance during fMRI scanning - measured in terms of corrected cumulative proximity (CCProx) to the goal - showed that a subgroup of older good performers attained comparable levels of search accuracy to the young while another subgroup of older poor performers exhibited consistently lower levels of search accuracy than both older good performers and the young. With regard to brain activations, young adults exhibited greater activations in the cerebellum and cuneus than all older adults, as well as older poor performers. Older good performers exhibited higher activation than older poor performers in the orbitofrontal cortex (BA 10/11), as well as in the cuneus and cerebellum. Brain-behavior correlations further showed that activations in regions involved in visuomotor control (cerebellum, lingual gyrus) and egocentric spatial processing (premotor cortex, precuneus) correlated positively with search accuracy (i.e., closer proximity to goal) in all participants. Notably, activations in the anterior hippocampus correlated positively with search accuracy (CCProx inversed) in the young but not in the old. Taken together, these findings implicated the orbitofrontal cortex and the cerebellum as playing crucial roles in executive and visuospatial processing in older adults, supporting the proposal of an age-related compensatory shift in spatial memory functions away from the hippocampus toward the prefrontal cortex.
Intersectionality: From Theory to Practice

Intersectionality as a framework and praxis has gathered significance in law and the social sciences over the past 20 years. This article begins by reviewing how intersectionality has been conceptu...
Boot camp: a first year seminar in CS1 labs

This paper presents novel solutions to a persistent and widespread problem: efficiently bridging the gap between high school and college. The first year seminar implemented at Shippensburg University is designed to rapidly develop the professionalism, observation, self-management, and new-skill acquisition strategies necessary for college success. This "boot camp" also lays out the degree concentrations available in the Computer Science department and outlines long-term goals, enabling incoming freshmen to quickly choose a path that will provide the greatest satisfaction and a clear goal to cling to during the lengthy acquisition of core skills that are the hallmark of their freshman and sophomore years. Of specific interest are the elements of the program that creatively replicate the demands of the discipline of computer science and of industry: observation, problem solving, and professionalism. Finally, the challenges of this course are outlined and possible solutions are suggested.
25 – Fourier Analysis

Publisher Summary One of the most remarkable results in mathematics is the discovery by Fourier that any reasonably well-behaved function f (x) can be represented as the sum of a (possibly infinite) set of sine and cosine functions. This discovery has had major theoretical and practical applications throughout mathematics and physical science. For example, Fourier transforms are useful for such diverse problems as solving differential equations, analyzing numerical methods, and filtering noise from a signal. The use of Fourier transforms in data analysis was revolutionized in the middle of the twentieth century by the development of algorithms that allows fast, efficient numerical calculation of Fourier transforms. These algorithms are referred to as fast Fourier transforms (hence the name FFT). Because of their widespread use and potentially heavy computational requirements, many variations of the FFT algorithm have been developed for particular applications or computer systems. Interactive Data Language (IDL) includes a general-purpose fast Fourier transform algorithm that can be accessed via the built-in FFT function. This chapter covers the basics of using the IDL fast Fourier transform (FFT). The IDL FFT function is a general-purpose complex fast Fourier transform. If the input signal is real, remember that the output from FFT is always complex.