cssi/SciSciGPT-SciSciNet huggingface dataset:
Which Clinicopathologic Factors Affect the Prognosis of Gingival Squamous Cell Carcinoma: A Population Analysis of 4,345 Cases.

Purpose The purpose of this study was to present the characteristics and survival outcomes of primary gingival squamous cell carcinoma (SCC). Materials and Methods We performed a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) tumor registry. Patients who received a diagnosis of primary gingival SCC were included in the analyses. The predictor variables were chosen from baseline demographic and tumor characteristics. The outcome of interest was survival, and Kaplan-Meier analyses were used to estimate rates of overall survival (OS) and disease-specific survival (DSS). Cox proportional hazards regression models were used for multivariate analyses. Results In total, 4,345 patients (mean age, 70.2 years) with primary gingival SCCs were identified. There was a significantly positive association between T category and both nodal and distant metastases. The 2-, 5-, and 10-year OS rates were 63.1%, 46.5%, and 28.1%, respectively, whereas the DSS rates were 78.2%, 70.7%, and 62.2%, respectively. Multivariate Cox proportional hazards regression showed that the independent predictors of overall and disease-specific death were older age, intermediate and high histologic grade, tumor size, nodal disease, and the absence of surgery. T4 classification was significantly associated with only DSS. Race, gingival location (maxillary vs mandibular), verrucous histology, and the presence of distant metastases did not significantly affect survival when all other predictors were controlled for. Conclusions Older age at diagnosis, higher grade, increased tumor size, nodal disease, and the absence of surgery were each individually associated with lower OS and DSS. Because of low nodal disease rates, both T1N0M0 lesions and verrucous subtypes may be candidates for neck observation.
Performance Support Guides

All of us have used a performance support guide in some way or another in our daily lives. The next time you put fuel in your car or truck, you will see a list of steps for the user to follow. All fuel pumps provide a brief set of instruction on how to insert your credit card, select the type of fuel you wish, and whether you want a receipt. The prompts are sometimes continued on the screen on the pump. Some prompts even go on to ask if you wish to purchase a car wash as well! Sometimes this information is presented completely with icons or simple pictures, in other instances it is presented as text, and in others as a combination of icons and text. Now that more cars are being powered by electric motors, electric recharging stations will also need to present a performance support guide to ensure that users know how to connect the charging station to their car’s outlet. Most of these users are doing this task for the first time, so that error is always a possibility, and doing it properly is critical for ensuring the recharge has occurred. Refueling or recharging our cars is a simple task that many of us perform on a regular basis, perhaps weekly. One would think we could just remember how to do it, and the information would be unnecessary. There remains the need for providing a performance support guide of some kind, to ensure that the intended activity is done correctly. Without it, there’s always the probability of making an error. This chapter addresses how to adapt a task analysis information to a performance support guide.
3031 Facilitators and Barriers in Screening Sexually Active Female Adolescents for Chlamydia Infection in the Suburban Practice Setting

OBJECTIVES/SPECIFIC AIMS: 1) Describe strategies pediatric providers perceive improve chlamydia screening of sexually active female adolescents (SA), and 2) describe barriers to regular screening of SA for chlamydia METHODS/STUDY POPULATION: Using qualitative methods, 14 general pediatric providers across 7 clinical sites in Vermont were interviewed to ascertain best practices and remaining challenges. Semi-structured interviews lasting 30-45 minutes were audiotaped and transcribed. Chlamydia screening rates provided by BCBS-VT were used to categorize participant responses across three performance tiers, data were coded, and themes identified within these tiers. RESULTS/ANTICIPATED RESULTS: Facilitators: When asked to describe facilitators of chlamydia screening, providers in the top tier of chlamydia screening emphasized the importance of adequate insurance to cover the cost of testing. Providers in the middle performance tier cited use of pre-visit questionnaires, and those in the bottom performance tier identified no best practices. Other strategies included improving physician confidence and awareness, establishing practice- and individual-level routines, and providing strong leadership and communication of local screening rates. Barriers: Across the 3 performance tiers, the most common challenges to consistent chlamydia screening were threats to patient confidentiality, cost of the screening test, and requirement for patient disclosure of sexual activity. Less commonly, providers were concerned that adolescent patients were not reliable to obtain screens off-site, or fill treatment prescriptions without the help of a parent. DISCUSSION/SIGNIFICANCE OF IMPACT: The need for systematic, confidential, and inexpensive means for screening SA for chlamydia was highlighted in both the best practices and challenges described by providers of pediatric care in the suburban practice setting. Policy and practice interventions may target these needs to improve the reproductive health of female adolescents.
Acoustic Characterization of Structural Ceramics

The ceramics silicon nitride (Si3N4) and silicon carbide (Si C) are becoming important structural materials for applications such as turbine blades, ball bearings, heat exchanger tubing, and combustion engine piston caps. The importance of structural ceramics stems from their high strength at elevated temperatures (1000°C-1400°C), thus making turbine engines more efficient in terms of energy conservation and reduced pollutants in combustion products. Structural ceramics are also light weight (density ≈ 3.28 × 103 kg/m3) and the raw materials (Si, C, N) are abundant, which reduces the cost of ceramic components over their metal and powder metal counterparts. The advantages of structural ceramics are somewhat offset by the fact that they are brittle; consequently very small defects can lead to a dramatic decrease in their strength.
Impacts of MRI frequency on RF-induced Heating for External Fixation with Insulating Material

This paper investigates the impacts of MRI operating frequency on the RF-induced heating for external fixation with insulating material. It is found that the trend of RF-induced heating varied with the dielectric constant of the insulating material is different at 1.5 T and 3 T. This fact is due to the resonance resulted from the inductance produced by the external fixation and the capacitance introduced by the insulating material.
An evaluation of public participation information for land use decisions: public comment, surveys, and participatory mapping

Public participation in the form of public meetings and written submissions has been criticised as a democratic ritual that fails to give citizens a real voice in government decisions. Participator...
Aortic Arch Thrombus and Pulmonary Embolism in a COVID-19 Patient.

Abstract Background Coronavirus disease 2019 (COVID-19) is associated with endothelial inflammation and a hypercoagulable state resulting in both venous and arterial thromboembolic complications. We present a case of COVID-19-associated aortic thrombus in an otherwise healthy patient. Case Report A 53-year-old woman with no past medical history presented with a 10-day history of dyspnea, fever, and cough. Her pulse oximetry on room air was 84%. She tested positive for severe acute respiratory syndrome coronavirus 2 infection, and chest radiography revealed moderate patchy bilateral airspace opacities. Serology markers for cytokine storm were significantly elevated, with a serum D-dimer level of 8180 ng/mL (normal Why Should an Emergency Physician Be Aware of This? Mural aortic thrombus is a rare but serious cause of distal embolism and is typically discovered during an evaluation of cryptogenic arterial embolization to the viscera or extremities. Patients with suspected hypercoagulable states, such as that encountered with COVID-19, should be screened for thromboembolism, and when identified, aggressively anticoagulated.
Optimization of Coaxial Magnetic Gear Design and Magnet Material Grade at Different Temperatures and Gear Ratios

Magnetic gears, like mechanical gears, transform power between different speeds and torques; however, magnetic gears’ contactless nature provides inherent potential benefits over mechanical gears. A genetic algorithm was used to optimize magnetic gears at different temperatures across a range of gear ratios. Using different magnet material grades on the different rotors and for the tangentially and radially magnetized magnets can slightly increase the specific torque relative to designs with a single magnet material. The high pole count rotor requires a magnet material with higher coercivity than that of the low pole count rotor magnet material, especially for designs with a large gear ratio. While increasing the temperature produces an exponential decay in the achievable specific torque, with a compounding reduction of about 0.4% for each degree Celsius, the temperature does not significantly affect the optimal geometric parameters and primarily affects the optimal materials. The gear ratio significantly affects the optimal geometric parameters and can impact the optimal magnet materials. Additionally, the genetic algorithm was employed to characterize the impact of stack length using 3D finite element analysis. Designs with shorter stack lengths favored thinner magnets and higher pole counts and may be able to use magnet materials with lower coercivities.
Federally-Chartered Corporations and Federal Jurisdiction

Although we typically think of corporations as creatures of state law, many corporations actually are chartered under federal law. These federally-chartered corporations include such public and quasi-governmental entities as Fannie Mae and the FDIC, but many federally-chartered corporations are private business corporations that compete directly with state-chartered companies. Congress has chartered railroads, construction companies, banks, savings associations, credit unions, and many other types of business entities, and the role of federal chartering continues to grow. Recently, there have been proposals for the creation of several new types of federal chartering authority, including federal charters for insurance companies, for securities firms, and for "universal financial services" firms.This article addresses an increasingly-important issue for federally-chartered corporations: the jurisdictional treatment that these corporations receive in federal court. Although federal corporations once could invoke federal jurisdiction based solely on their federal charter, that no longer is the case. And unlike state-chartered corporations, whose state citizenship is defined by 28 U.S.C. Section 1332(c)(1), there is no single statute defining the citizenship of federally-chartered corporations. The few scattered statutes that do exist, for national banks and other select categories of federal corporations, use inconsistent tests for citizenship. Other federal corporations, not covered by these statutes, must try to fit within the judicially-created "localization" rule. This rule, though, has been applied inconsistently by the courts and often leads to situations in which a federal corporation cannot gain access to federal court when a state counterpart could. The article analyzes the current disparities and inconsistencies in the law and proposes the enactment of a new federal statute, similar to Section 1332(c)(1), that would lead to jurisdictional parity between state and federal corporations.
Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D).

Abstract Aims Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D. Methods Pilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period. Results Forty-five T2D participants on metformin monotherapy (mean age 57 ± 8 years, duration 7 ± 6 years, HbA1c 7.8 ± 1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride. Conclusions Short term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN. Clinical trial registration: NCT02973477
Abstract 1782: Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development

Lung cancer is the most common cause of cancer-related death worldwide in both men and women. The overall survival of lung cancer remains poor due to limitations in diagnostic and therapeutic strategies. Therefore, the development of novel biomarkers is urgently needed to improve patient prognosis. Growing evidence has demonstrated alterations of the normal microbiome in lung cancer. Dysbiosis may alter normal microbiota-host interactions and induce immune dysregulation, and therefore contribute to the promotion of tumorigenesis. Although multiple studies show an association between dysbiosis, host immune response and tumorigenesis, the underlying mechanisms are still unclear. We previously characterized a distinct group of taxa that are enriched in lung adenocarcinoma and squamous cell carcinoma. Among these taxa, Acidovorax spp. were associated with cigarette smoking and TP53 mutations, with Acidovorax temperans identified by full-length 16S sequencing. We hypothesized that enrichment of A. temperans in the lung microbial community may modulate the immune microenvironment and therefore contribute to tumor development. We used an autochthonous mouse model of lung adenocarcinoma, in which tumorigenesis is driven by oncogenic K-Ras and a gain-of function mutant p53 under the control of the Cre-lox system. We administered biweekly intranasal instillations of A. temperans to mimic the effects of chronic tobacco smoking. Following bacterial instillation, the lung tumor development was determined by magnetic resonance imaging (MRI) at 13 weeks post Ad-Cre instillation. Mice challenged with A. temperans exhibited significantly larger tumor burden and a deleterious effect on survival compared to the sham group. Given the importance of the immune system in modulating tumor development, we then investigated whether A. temperans exposure induced changes in the immune microenvironment through high parametric flow cytometry post 5th instillation and post MRI. Lungs from mice instilled with A. temperans showed an increased number of total leukocytes. The vast majority of leukocytes were pro-inflammatory cells and predominantly neutrophils. Moreover, we also found an increase in CD4+ T cells and double negative T cells, and an increase in RORγt+/IL17+ subpopulations in both of these T cell groups. Consistent with these results, the IL-17 expression level was upregulated in response to A. temperans instillation. Taken together, these results indicate that A. temperans exposure induces a robust pro-inflammatory response, thereby increasing immune infiltration in the tumor microenvironment and promoting development of lung adenocarcinoma. Citation Format: Chenran Zhang, Natalia von Muhlinen, Araya Romina, Joshua Stone, Romina Goldszmid, Curtis Harris. Acidovorax temperans modulates the host immune microenvironment to promote lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1782.
Neural autopilot and context-sensitivity of habits

This paper is about the background of two new ideas from neuroeconomics for understanding habits. The main idea is a two-process ‘neural autopilot’ model. This model hypothesizes that contextually cued habits occur when the reward from the habitual behavior is numerically reliable (as in related models with an ‘arbitrator’). This computational model is lightly parameterized, has the essential ingredients established in animal learning and cognitive neuroscience, and is simple enough to make nonobvious predictions. An interesting set of predictions is about how consumers react to different kinds of changes in prices and qualities of goods (‘elasticities’). Elasticity analysis expands the habit marker of insensitivity to reward devaluation, and other types of sensitivities. The second idea is to use machine learning to discover which contextual variables seem to cue habits, in field data.
CABG versus PCI in the Treatment of Unprotected Left Main Disease in Diabetics: A Literature Review

The approach to left main coronary artery disease (CAD) in diabetic patients has been extensively debated. Diabetic patients have an elevated risk of left main disease in addition to multivessel disease. Previous trials have shown increased revascularization rates in percutaneous coronary intervention compared with coronary artery bypass grafting (CABG) but overall comparable outcomes, although many of these studies were not using the latest stent technology or CABG with arterial revascularization. Our aim is to review the most recent trials that have recently published long-term follow-up, as well as other literature pertaining to left main disease in diabetic patients. Furthermore, we will be discussing some future treatment strategies that could likely create a paradigm shift in how left main CAD is managed.
Pulmonary Hypertension in Adults with Congenital Heart Disease

Pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) affects 5% to 10% of adults with CHD and is associated with significant morbidity and mortality. PAH-CHD develops as a consequence of intracardiac or extracardiac systemic-to-pulmonary shunts that lead to pulmonary vascular remodeling through a pathologic process that is similar to other causes of PAH. Eisenmenger syndrome is the most severe phenotype of PAH-CHD and is characterized by severe elevation in pulmonary vascular resistance, with shunt reversal causing hypoxemia and central cyanosis. The primary management strategy for most patients with PAH-CHD is medical therapy, although defect closure is considered in select cases.
Temozolomide Induced Bone Marrow Suppression- a Single Institution Outcome Analysis and Review of Literature

Background: Severe myelosuppression (MS) and bone marrow failure (BMF) are rare but well characterized adverse effect of temozolomide (TMZ). The existing literature is limited to case reports and data reported to regulatory agencies, which usually describe very severe cases and lack long term and detailed follow-up. Methods : We identified cases of myelosuppression attributed to TMZ seen at the Mayo clinic, from 1998-2014. We also performed a literature (PubMed) search to identify published cases of TMZ induced MS and BMF. TMZ induced MS was defined as a decrease in at least 2 cell lines below normal that was clinically attributable to TMZ and persisted for > 28 days after the last TMZ dose. Severe MS was defined as bone marrow cellularity of Results : A total of 15 Mayo patients and 10 published cases were identified. The baseline characteristics of patients are shown in table 1. The median interval between initiation of TMZ and diagnosis of MS was 48 days (range 26-121). The hematologic outcomes of the group are shown in table 2. Seventeen patients developed neutropenic fever, 4 had severe sepsis, and 6 experienced bleeding complications. Kaplan-Meier recovery curves for each cell line are shown in the figure. Myelosuppression was fatal in 3 cases. Most patients recovered their ANC (median-62 days, range 28-180). Persistent thrombocytopenia was seen in 19 patients, without evidence for clonal evolution or myelodysplasia. Four patients remain dependent on growth factor support (G-CSF and thrombopoietin agonists). Conclusion : MS is usually a non-fatal complication of TMZ. Most cell lines recover spontaneously and adequately with the exception of platelets, which can remain significantly suppressed for prolonged periods. Infectious complications are very common. Most patients respond to supportive care, including the use of growth factors. Disclosures No relevant conflicts of interest to declare.
Vascular Endothelial Growth Factor and Osteogenic-Angiogenic Coupling

Publisher Summary This chapter focuses on vascular endothelial growth factor (VEGF) bone biology. It highlights the roles and regulation of VEGF receptor signaling during bone development, osteogenic–angiogenic coupling, matrix remodeling, fracture repair, and skeletal mineral metabolism. Bone never forms without vascular interactions. The vasculature provides the conduit for calcium, phosphate, hematopoietic, hormonal, and nutrient flux necessary for matrix synthesis, mineralization, and calcium mobilization. It provides the organizational structure and rate-limiting “point-of-reference” for Haversian bone formation, remodeling, and repair. Moreover, the vasculature provides a sustentacular niche and source of adult mesenchymal stem cells, including osteoprogenitors. During fracture repair, paracrine endothelial-mesenchymal signaling interactions are activated, recapitulating features of the epithelial-mesenchymal interactions that drive bone morphogenesis during embryonic development. Recent evidence suggests that circulating, marrow-derived endothelial progenitor cells (EPCs) may be delivered by the vasculature to sites of bone formation, and contribute not only to mature endothelial populations, but also to microvascular smooth muscle cells and osteoblast lineages during skeletal growth and fracture repair. In conclusion, VEGFA has emerged as the prototypic osteogenic-angiogenic coupling factor for bone-vascular interactions.
Search for volatiles on icy satellites: I. Europa

NASA IRTF reflectance spectra of unprecedented precision, obtained for the leading and trailing sides of Europa, are presently noted to no longer show the apparent absorptions seen in 1980 and 1985. It is presently suggested that if the weak absorptions seen in the 1980 and 1985 data are real, they may indicate the transient spectroscopic presence of a molecular component on Europa's trailing side that differs from the water ice known to be the dominant constituent of the surface.
γComponent, a New Myofibrillar Protein of Skeletal Muscle

Abstract A new myofibrillar protein, tentatively named γ component, was purified to a homogeneous state from Ebashi's partially purified preparation of skeletal relaxing protein. The γ component, purified by passing it through a DEAE-cellulose column, was shown to be a myofibrillar protein different from known myofibrillar proteins such as tropomyosin, troponin, and α-actinin by gel electrophoresis, gel filtration, ultracentrifugation, and amino acid composition.
Vascular Epiphytes: General Biology and Related Biota

Epiphytes (plants which grow on other plants, not parasitically but for support), comprise more than one-third of the total vascular flora in some tropical forests. Growing within tropical forest canopies, epiphytes are subject to severe environmental constraints, and their diverse adaptations make them a rich resource for studies of water balance, nutrition, reproduction and evolution. This book synthesizes the body of information from research on epiphytes and their relations with other tropical biota, and provides a comprehensive overview of basic functions, life history, evolution, and the place of epiphytes in complex tropical communities. Tropical ecologists and zoologists as well as plant scientists will find this volume a useful guide to research on the twenty-five thousand species of epiphytes which root in the crowns of tropical trees.
Interactive Graphics for Simulating Construction Operations

This paper describes a project designated to develop, test, implement and document a practical, low-cost, terminal and microcomputer-based interactive simulation and graphics systems and related courseware to serve as a teaching laboratory. This research will bring together essential work from three important fields: (1)Time-lapse photographic documentation of unit operations; (2)computer-based simulation modeling; and (3)interactive man-computer graphics. The purpose is to create a system for statistical documentation of discrete unit operations, transfer and reduction of data by directly synchronizing the time-lapse film with the real-time computer system, and analysis via simulation modeling and interactive man-computer graphics. By combining these three technologies, a system is obtained whose analytical power far exceeds the sum of its parts.
High School Dropouts After They Exit School: Challenges and Directions for Sociological Research

Sociological research on high school dropouts is largely concerned with who drops out of school and why. Research on the consequences of dropping out is less common. There are clear theoretical reasons to expect dropping out to have a direct and negative effect on life outcomes; however, empirically evaluating these theories is difficult because students who drop out are different from high school graduates in meaningful and complex ways. In this article, I first provide a brief review of sociological research on high school dropouts, emphasizing the demographics of dropouts and reasons for dropping out. I then discuss the possible role of human capital differences, signaling theory, and social closure in creating worse outcomes for high school dropouts and outline the empirical challenges to researching the effects of dropping out. I conclude by discussing avenues for future research and important unanswered questions about the consequences of dropping out.
Microarray analysis of gene expression in the aging human retina.

Purpose To develop gene expression profiles of young and elderly human retinas and identify candidate genes for aging-associated retinal diseases. Methods Gene microarray slides containing 2400 human genes (primarily neuronal) were hybridized to biotin or dinitrophenyl (DNP)-labeled target cDNAs that were synthesized using total RNAs from young (13-14 years) and elderly (62-74 years) human retinas. Hybridization signals were visualized with cyanine (Cy)-5 or Cy-3 fluorescent reporter molecules, and the fluorescence intensities of the images were analyzed by computer. Northern blot analysis and real-time quantitative reverse transcription PCR (qRT-PCR) were performed to validate the microarray results. Results Of the 2400 genes represented on the microarray slides, more than 50% hybridized to the retinal cDNA targets. Expression of a majority of these genes was not altered during aging; nonetheless, changes in the expression of 24 genes were detected between young and elderly retinas. These genes could be clustered into four categories: energy metabolism, stress response, cell growth, and neuronal transmission/signaling. Northern blot analysis and qRT-PCR results confirmed the changes in expression of 8 of 10 genes examined. Conclusions Using commercially available slide microarrays, the authors show that aging of the human retina is associated with changes in patterns of gene expression. This analysis suggests that pathways involved in stress response and energy metabolism play key roles in retinal aging. These studies demonstrate the utility of gene microarrays in identifying global patterns of retinal gene expression and lay the foundation for future studies defining the genetic basis of aging-associated retinal diseases, such as age-related macular degeneration.
Chapter two : May you live in interesting times : The impact of revolutions and shifting paradigms on public services staff

L'un des themes les plus courants pour decrire la transformation des bibliotheques est bien access vx. ownership. Apres une description de cette position et une definition du service public en bibliotheque, l'auteur developpe l'evolution du role des bibliothecaires dans chaque domaine: service de reference, service de pret, formation des utilisateurs, developpement des collections...
Isolation of Glyoxysomes from Pumpkin Cotyledons

Peroxisomes are single-membrane-bound organelles found in virtually all eukaryotes. In plants, there are several classes of peroxisomes. Glyoxysomes are found in germinating seedlings and contain enzymes specific for the glyoxylate cycle, including isocitrate lyase and malate synthase. After seedlings become photosynthetic, leaf peroxisomes participate in reactions of the photorespiration pathway and contain characteristic enzymes such as glycolate oxidase and hydroxypyruvate reductase. As leaves begin to senesce, leaf peroxisomes are transformed back into glyoxysomes. Root peroxisomes in the nodules of legumes, for example, sequester enzymes such as allantoinase and uricase, which contribute to nitrogen metabolism in these tissues. Thus, peroxisomes participate in many metabolic pathways and contain specific enzyme complements, depending on the tissue source. All peroxisomes contain catalase to degrade hydrogen peroxide and enzymes to accomplish β-oxidation of fatty acids. Glyoxysomes can be isolated from pumpkin cotyledons by standard differential centrifugation and density separation, as described in this article. Keywords: glyoxysomes; peroxisomes; protein import
Carfilzomib: a novel agent for multiple myeloma

Objectives Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients. Key findings Carfilzomib is a selective proteasome inhibitor that differs structurally and mechanistically from bortezomib. In patients’ whole-blood and peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and immunoproteasomal activity by 70‐80%. Approved carfilzomib dosing is based on body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle (20 mg/m 2 in cycle 1; 27 mg/m 2 in cycle 2+). Premedication with dexamethasone and adequate hydration are recommended to reduce the risk of adverse events. The median t1/2 of carfilzomib is short (0.29‐0.48 h), with no accumulation detected between doses. In clinical studies in relapsed and refractory MM. and in combinations in newly diagnosed MM, single-agent carfilzomib demonstrated significant durable activity, good tolerability and a favourable safety profile, supporting its extended use. Conclusions Carfilzomib represents an important addition to the treatment armamentarium for patients with relapsed and/or refractory MM, and studies are underway evaluating the role of single-agent carfilzomib in additional clinical settings as well as in different combinations.
The conversion of a high order programming language from floating-point arithmetic to range arithmetic

Floatmg-pomt arithmetic is the computation arithmetic that most high-level programming languages provide. A well-known drawback of this arithmetic is that when extended calculations are performed, the final answers have arithmetic is that varies widely. Under certain conditions the error is so large as to completely invalidate the results, and the person doing the computation is often unaware that this has occurred.
Stability of an Uncooled Segment of a High-Temperature Superconductor

If the level of a liquid cryogen inadvertently falls below the top of a magnet winding, it may expose a segment of the conductor. Depending on the length of the uncooled segment and on how the matrix resistivity varies with temperature, zero, one, or two steady normal states may be possible. The stability of the various steady states, the conditions under which they appear, their energies of formation, and the voltages they produce are studied in this paper.
Bayesian co‐clustering

Co-clustering means simultaneously identifying natural clusters in different kinds of objects. Examples include simultaneously clustering customers and products for a recommender application; simultaneously clustering proteins and molecules in microbiology; or simultaneously clustering documents and words in a text mining application. Important insights into a problem can be gained by understanding the interactions between clusters for the different kinds of objects. This paper considers Bayesian models for co-clustering. The Bayesian approach begins by developing a model for the data generating process, and inverting that model through Bayesian inference to infer cluster membership, learn characteristics of the clusters, and fill in missing observations. We consider a basic Bayesian clustering model and several extensions to the model. Experimental evaluations and comparisons among the clustering methods are presented. WIREs Comput Stat 2015, 7:347–356. doi: 10.1002/wics.1359 For further resources related to this article, please visit the WIREs website.
An Enhanced Recursive Stopping Rule for Steepest Ascent Searches in Response Surface Methodology

Abstract In traditional Response Surface Methods (RSM), running a first order experimental design is usually followed by a steepest ascent search using the vector of parameter estimates as an approximation to the gradient. In the presence of variability in the responses, there is a need for a stopping rule to determine the optimal point in the search direction. Two formal stopping rules have been proposed in the literature, Myers and Khuri's (MK) stopping rule and Del Castillo's Recursive Parabolic Rule (RPR). The first rule requires the specification of an initial guess on the number of steps required to reach the optimum, while the performance of the second rule has only been studied for quadratic responses. This paper proposes some modifications to the recursive parabolic rule in order to increase its robustness for non-quadratic responses. The modifications consist of using only a fraction of the experiments made along the search, the estimation of all the parameters in the parabolic model, and the ut...
Are intermediate depth earthquakes caused by plastic faulting

Abstract The increase in confining pressure and temperature with depth precludes frictional sliding beyond a few tens of kilometers, yet earthquakes occur to depths greater than 600 km. Although rock failure is often conceptualized as either brittle under low pressure and temperature or ductile at higher pressure and temperature, an intermediate brittle-like failure mode, sometimes called “transitional” or “semi-brittle faulting”, is well known experimentally. In contrast to brittle and ductile failure, models for semi-brittle terminal failure strength are lacking. We show that semi-brittle failure is consistent with the dictates of adiabatic instabilities that result in failure via plastic faulting. Although adiabatic instabilities have been suggested as a possible cause of deep ( > 500 km ) earthquakes, extrapolation of laboratory semi-brittle faulting data using the theory of plastic faulting with a rheology and geotherm typical of subducting oceanic crust indicates that adiabatic instabilities are more likely at intermediate depths to about 300 km.
Degradation of high-level waste glass under simulated repository conditions

The internal waste package environment that contains corrosion products from the containers may have a significant influence on waste form degradation. Leaching experiments of two simulated high-level waste glasses (WVDP Ref. 6 and DWPF Blend 1) were carried out in aqueous solutions of FeCl2 and FeCl3 at temperatures of 40, 70, and 90 °C that simulate the possible aqueous environment inside the breached waste packages. Both solution pH and the presence of corrosion species such as iron chloride were found to be major contributing factors to the net glass durability. Model abstraction and performance assessment analyses using rate expressions showed that the presence of corrosion products enhances glass dissolution and increases the subsequent release of radionuclides to the environment.
Response of patients with chronic obstructive lung disease to the regular administration of nebulized isoproterenol. A double-blind crossover study.

The effect of the regular use of nebulized isoproterenol in 14 patients with symptomatic chronic obstructive lung disease (COLD) was evaluated in a double-blind crossover 16-week study. FEV 1 , FVC and SG aw were measured before and 45 minutes after bronchodilator therapy every two weeks, while arterial blood gases were measured every eight weeks, before and 45 minutes after bronchodilator therapy. When the patients were considered as a group, there was no significant difference in mean symptom scores or objective pulmonary functions during the drug and placebo periods. Four patients had significantly higher (p l co .
Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney.

The mammalian metanephric kidney is derived from the intermediate mesoderm. In this report, we use molecular fate mapping to demonstrate that the majority of cell types within the metanephric kidney arise from an Osr1+ population of metanephric progenitor cells. These include the ureteric epithelium of the collecting duct network, the cap mesenchyme and its nephron epithelia derivatives, the interstitial mesenchyme, vasculature and smooth muscle. Temporal fate mapping shows a progressive restriction of Osr1+ cell fates such that at the onset of active nephrogenesis, Osr1 activity is restricted to the Six2+ cap mesenchyme nephron progenitors. However, low-level labeling of Osr1+ cells suggests that the specification of interstitial mesenchyme and cap mesenchyme progenitors occurs within the Osr1+ population prior to the onset of metanephric development. Furthermore, although Osr1+ progenitors give rise to much of the kidney, Osr1 function is only essential for the development of the nephron progenitor compartment. These studies provide new insights into the cellular origins of metanephric kidney structures and lend support to a model where Osr1 function is limited to establishing the nephron progenitor pool.
Self-plagiarism in computer science

We are all too aware of the ravages of misconduct in the academic community. Students submit assignments inherited from their friends, online papermills provide term papers on popular topics, and occasionally researchers are found falsifying data or publishing the work of others as their own.This article examines a lesser-known but potentially no less bothersome form of scientific misconduct, namely self-plagiarism. Self-plagiarism occurs when authors reuse portions of their previous writings in subsequent research papers. Occasionally, the derived paper is simply a retitled and reformatted version of the original one, but more frequently it is assembled from bits and pieces of previous work.
New scalar and vector elementary functions for the IBM system/370

Algorithms have been developed to compute short- and long-precision elementary functions: SIN, COS, TAN, COTAN, LOG, LOG10, EXP, POWER, SQRT, ATAN, ASIN, ACOS, ATAN2, and CABS, in scalar (28 functions) and vector (22 functions) mode. They have been implemented as part of the new VS FORTRAN library recently announced along with the IBM 3090 Vector Facility. These algorithms are essentially table-based algorithms. An important feature of these algorithms is that they produce bitwise-identical results on scalar and vector System/370 machines. Of these, for five functions the computed value result is always the correctly rounded value of the infinite-precision result. For the rest of the functions, the value returned is one of the two floating-point neighbors bordering the infinite-precision result, which implies exact results if they are machine-representable. For the five correctly rounded elementary functions, scalar and vector algorithms are designed independently so as to optimize performance in each case. For other functions, the bitwise-identical constraint leads to algorithms which compromise between scalar and vector performance. The authors have been able to design algorithms where this compromise is minimal and thus achieve very good performance on both scalar and vector implementations. For test measurements on high-end System/370 machines, scalar functions aremore » always faster (sometimes by as much as a factor of 2.5) as compared to the old VS FORTRAN library. The vector functions are usually two to three times faster than scalar functions.« less
Design status of the CMS forward pixel detector

Abstract The CMS experiment at the CERN LHC includes a pixel system for tracking and vertexing charged particles. This system consists of two parts: the central and the forward detectors. This paper describes the main features of the forward detectors, which are being built by a collaboration of physicists from the USA.
Sensitive, Site-Specific, and Stable Vibrational Probe of Local Protein Environments: 4-Azidomethyl-l-Phenylalanine

We have synthesized the unnatural amino acid (UAA), 4-azidomethyl-l-phenylalanine (pN3CH2Phe), to serve as an effective vibrational reporter of local protein environments. The position, extinction coefficient, and sensitivity to local environment of the azide asymmetric stretch vibration of pN3CH2Phe are compared to the vibrational reporters: 4-cyano-l-phenylalanine (pCNPhe) and 4-azido-l-phenylalanine (pN3Phe). This UAA was genetically incorporated in a site-specific manner utilizing an engineered, orthogonal aminoacyl-tRNA synthetase in response to an amber codon with high efficiency and fidelity into two distinct sites in superfolder green fluorescent protein (sfGFP). This allowed for the dependence of the azide asymmetric stretch vibration of pN3CH2Phe to different protein environments to be measured. The photostability of pN3CH2Phe was also measured relative to the photoreactive UAA, pN3Phe.
Cimetidine protection against alpha-amanitin hepatotoxicity in mice: A potential model for the treatment of Amanita phalloides poisoning

The ingestion of the mushroom Amanita phalloides is associated with hepatic necrosis appearing clinically two to three days after ingestion. The mechanism of this toxicity is unknown, and no reliable antidote is available. Because of the similarity of Amanita poisoning to other toxins affecting cytochrome P 450 , we investigated the use of cimetidine (as a P 450 cytochrome inhibitor) as an antidote against a primary toxin of the mushroom alpha-amanitin. Mice injected with alpha-amanitin and given cimetidine either prophylactically or within six hours showed histologic protection from the hepatic damage seen in control mice. Control animals displayed significant mitochondrial changes when examined by electron-microscopy, while the mitochrondria of the cimetidine-treated animals were preserved, suggesting a possible site for toxin action. Further trials will be necessary before treatment of human cases with cimetidine is indicated.
Carrier transport across heterojunction interfaces

Abstract A general theory is presented to describe the carrier transport across heterojunction interfaces. In matching the boundary conditions at the interface, the conservation of total energy and perpendicular momentum is assumed and the difference of effective masses on two sides of the junction is taken into account. The quantum mechanical transmission coefficient is calculated by a combined numerical and WKB method. Application of the present model to an AlxGa1−xAsGaAs N-n heterojunction is performed and it gives rise to rectifying characteristics together with non-saturated reverse current. Comparison with the classical thermionic emission model is made to show the significance of tunneling and effect of quantum mechanical reflection.
An examination of chemically-modified silica surfaces using fluorescence spectroscopy

Abstract Animated microparticulate silica gel was derivatized with the fluorescent tag, dansyl chloride, to produce a chemically-modified silica surface that could be examined by fluorescence spectroscopy; also a dansylated silica was further derivatized with various alkyl functionalities. The labelled silicas were introduced into solvents and solvent mixtures of different polarities and the emission spectra obtained were compared with the spectra of a model compound, n -propyldansylamide, in the same solvents. It was found that residual amine groups, as well as unreacted silanol groups, produced a polar surface environment that was reflected in the emission maximum of the spectrum of the modified silica. The degree of residual surface polarity also appears to be a function of the aminopropylsilane reagents used.
Manipulating Processing Difficulty of Reading Comprehension Questions: The Feasibility of Verbal Item Generation

Based on a previously validated cognitive processing model of reading comprehension, this study experimentally examines potential generative components of text-based multiple-choice reading comprehension test questions. Previous research (Embretson & Wetzel, 1987; Gorin & Embretson, 2005; Sheehan & Ginther, 2001) shows text encoding and decision processes account for significant proportions of variance in item difficulties. In the current study, Linear Logistic Latent Trait Model (LLTM; Fischer, 1973) parameter estimates of experimentally manipulated items are examined to further verify the impact of encoding and decision processes on item difficulty. Results show that manipulation of some passage features, such as increased use of negative wording, significantly increases item difficulty in some cases, whereas others, such as altering the order of information presentation in a passage, did not significantly affect item difficulty, but did affect reaction time. These results suggest that reliable changes in difficulty and response time through algorithmic manipulation of certain task features is feasible. However, non-significant results for several manipulations highlight potential challenges to item generation in establishing direct links between theoretically relevant item features and individual item processing. Further examination of these relationships will be informative to item writers as well as test developers interested in the feasibility of item generation as an assessment tool.