cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4177: Anticancer agent Aminoflavone restores the expression of tumor suppressor miRNA 26a and inhibits putative stemness biomarker α6-integrin in Tamoxifen resistant cells

Despite the efficacy of anti-estrogen agent Tamoxifen, commonly used to treat patients with estrogen receptor positive (ER + ) tumors, up to 40% of patients experience recurrence. Breast tumor-initiating cells (TICs), or breast cancer stem cells, exhibit Tamoxifen resistance and contribute substantially to recurrence. We recently demonstrated that investigational anticancer agent Aminoflavone (AF) disrupts mammospheres (in vitro clusters of cells enriched with TICs) by thwarting the expression of α6-integrin. In the current study, we found AF potently inhibited Tamoxifen resistant (TamR) cell growth and blocked Tamoxifen-mediated stimulation of TamR cell proliferation using the Alamar Blue assay. qPCR analyses revealed α6-integrin expression was significantly elevated in ER + breast cancer cell models of acquired and de novo Tamoxifen resistance relative to Tamoxifen sensitive cells. In particular, AF decreased the expression of both A and B variants of α6-integrin, the B variant being essential for TIC function. Western blotting revealed AF reduced total α6-integrin expression in TamR cells. Furthermore, we found that an anti-α6-integrin blocking antibody sensitized TamR cells to the active Tamoxifen metabolite, 4-hydroxy-Tamoxifen, and enhanced the efficacy of AF in these cells. AF also reduced the protein expression of p-Src, a downstream target of α6-integrin that is linked to Tamoxifen resistance and decreased breast cancer survival. In addition, miRNA sequencing of Tamoxifen sensitive and TamR mammospheres revealed differential expression of several miRNAs. Notably, miR-26a expression was down-regulated 2-fold in TamR mammospheres compared to Tamoxifen sensitive mammospheres and AF restored miR-26a expression 5-fold in TamR mammospheres. Using miRNA target prediction algorithms TargetScan and PicTar, we found miR-26a binding sites on the α6-integrin promoter. Taken together, our data suggest that AF re-expresses tumor suppressor miR-26a and inhibits the α6-integrin/Src signaling axis to reduce TIC capacity and counteract Tamoxifen resistance. Citation Format: Petreena Campbell, Leah Rowland, Anna Opoku-Agyeman, Nichole Mavingire, Ubaldo Soto, Gayathri Nagaraj, Yonghong Zhang, Sean (Xin) Chen, Charles Wang, Eileen Brantley. Anticancer agent Aminoflavone restores the expression of tumor suppressor miRNA 26a and inhibits putative stemness biomarker α6-integrin in Tamoxifen resistant cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4177. doi:10.1158/1538-7445.AM2017-4177
Transthyretin deposition promotes progression of osteoarthritis.

Summary Deposition of amyloid is a common aging-associated phenomenon in several aging-related diseases. Osteoarthritis (OA) is the most prevalent joint disease, and aging is its major risk factor. Transthyretin (TTR) is an amyloidogenic protein that is deposited in aging and OA-affected human cartilage and promotes inflammatory and catabolic responses in cultured chondrocytes. Here, we investigated the role of TTR in vivo using transgenic mice overexpressing wild-type human TTR (hTTR-TG). Although TTR protein was detected in cartilage in hTTR-TG mice, the TTR transgene was highly overexpressed in liver, but not in chondrocytes. OA was surgically induced by destabilizing the medial meniscus (DMM) in hTTR-TG mice, wild-type mice of the same strain (WT), and mice lacking endogenous Ttr genes. In the DMM model, both cartilage and synovitis histological scores were significantly increased in hTTR-TG mice. Further, spontaneous degradation and OA-like changes in cartilage and synovium developed in 18-month-old hTTR mice. Expression of cartilage catabolic (Adamts4, Mmp13) and inflammatory genes (Nos2, Il6) was significantly elevated in cartilage from 6-month-old hTTR-TG mice compared with WT mice as was the level of phospho-NF-κB p65. Intra-articular injection of aggregated TTR in WT mice increased synovitis and significantly increased expression of inflammatory genes in synovium. These findings are the first to show that TTR deposition increases disease severity in the murine DMM and aging model of OA.
Acute Disseminated Encephalomyelitis Followed by Recurrent or Monophasic Optic Neuritis

Acute disseminated encephalomyelitis (ADEM) is typically a monophasic demyelinating disease in young children. When relapses occur after ADEM, chronic diseases such as multiple sclerosis and neuromyelitis optica are suspected. A new clinical phenotype, ADEM followed by recurrent or monophasic optic neuritis in pediatric patients, has been proposed. We present the case of a young female with encephalopathy and polyfocal neurologic signs meeting criteria for ADEM, who subsequently had three relatively similar such relapses with new silent brain lesions. One year after her initial presentation, she developed relapses only affecting the optic nerves with substantial resolution of all other brain and spinal cord lesions on MRI. She did not have aquaporin-4 antibodies in the serum or cerebrospinal fluid. Similarly, oligoclonal bands were absent from the CSF during multiple attacks. Her clinical phenotype, laboratory findings, and imaging are consistent with ADEM followed by recurrent or monophasic optic neuritis. Collaborative outcome studies are needed to guide therapy and determine the prognosis of this rare disorder.
Technical factors are associated with complications and repeat intervention in neonates undergoing transcatheter right ventricular decompression for pulmonary atresia and intact ventricular septum: results from the congenital catheterisation research collaborative.

BACKGROUND Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described. METHODS This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention. RESULTS A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2-5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter. CONCLUSION Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.
Cell cycle deregulation in breast cancer: insurmountable chemoresistance or Achilles' heel?

Deregulation of the G1 cyclin, cyclin E, has been shown to be both the most powerful predictor of prognosis in early stage breast cancer as well as a significant determinant of tumor aggressiveness.1,2 It may also contribute to treatment failure due to chemoresistance. Because some form of cell cycle deregulation is present in all malignant cells,3 increasing understanding of these processes is starting to provide new opportunities to overcome the cells’ resistance mechanisms.
Integrating Constraint and Relational Database Systems

Constraint databases are a generalization of relational databases and can finitely represent infinite relations. The high expressiveness of constraint databases makes them a promising data model for representing spatial and spatiotemporal information. On the other hand, relational database systems are predominantly used for traditional applications and have a proven record of providing efficient querying and management of business data. It is more cost-effective to integrate constraint databases with the existing relational database systems than to build a completely new constraint database system from scratch. This paper proposes a way to integrate the constraint data model and query languages with a relational database system. It introduces a new relational data type to represent constraint data. It also provides several new relational database operators to query the constraint data.
Learning in simulated environments: An assessment of 4-week retention outcomes

Simulations offer the benefits of a safer and more accessible learning environment, where learners can practice until the point of proficiency. While research into the effectiveness of simulations as learning tools has found tangible benefits, fewer studies have examined retention and differences between high and low fidelity simulations. This research sought to supplement the literature in this domain by investigating whether participants who learned to construct an electrical circuit using a 2D or 3D breadboard simulation could achieve comparable learning, transfer, and retention outcomes to those who learned using a physical breadboard. The influence of learner characteristics - cognitive ability and goal orientation - were also evaluated. This study had two parts: a cross-sectional portion that examined learning and transfer outcomes and a longitudinal portion that examined retention outcomes after a 2 and 4-week period. The cross-sectional analysis included 70 participants and the longitudinal analysis included 40 participants. The results found that the physical fidelity of the learning environment significantly impacted several transfer outcomes (construction and construction time) but not retention outcomes. Cognitive ability was a significant predictor of learning (gain score, circuit design score) and retention (posttest scores, construction time) outcomes. Learning goal orientation significantly predicted circuit construction over time and measurement occasion significantly predicted posttest scores and interacted with fidelity to predict circuit design score. The study demonstrated that simulated environments can lead to comparable, or better, proficiency than physical environments. These findings have implications for the design and implementation of simulated environments, specifically for courses delivered in an online setting.
Complex between a Multicrossover DNA Nanostructure, PX-DNA, and T7 Endonuclease I

Paranemic crossover DNA (PX-DNA) is a four-stranded multicrossover structure that has been implicated in recombination-independent recognition of homology. Although existing evidence has suggested that PX is the DNA motif in homologous pairing (HP), this conclusion remains ambiguous. Further investigation is needed but will require development of new tools. Here, we report characterization of the complex between PX-DNA and T7 endonuclease I (T7endoI), a junction-resolving protein that could serve as the prototype of an anti-PX ligand (a critical prerequisite for the future development of such tools). Specifically, nuclease-inactive T7endoI was produced and its ability to bind to PX-DNA was analyzed using a gel retardation assay. The molar ratio of PX to T7endoI was determined using gel electrophoresis and confirmed by the Hill equation. Hydroxyl radical footprinting of T7endoI on PX-DNA is used to verify the positive interaction between PX and T7endoI and to provide insight into the binding region. Cleava...
Corporal Punishment and Children’s Mental Health: Opportunities for Prevention

Many genetic, epigenetic, and social environmental factors play a role in children’s emotional and cognitive development and determine critical mental processes, including the ability to regulate emotional states, maintain internal milieu in the face of stressors, and take part in interpersonal relationships. Children experience the environment through observation and participation plus formal teaching and their parents’ approach to discipline. In its broadest sense, discipline involves the ways parents help children acquire knowledge of the values and normative behaviors of the society in which they will function as adults. In common parlance, however, discipline is synonymous with punishment, either emotional, physical, or a combination of the two. Many parents continue to have positive attitudes toward the use of physical punishment. Parents’ own experiences as children, their mood and sense of stress as adults, and prevailing social norms all influence the likelihood that they will use physical punishment. A number of arguments can be advanced for reducing the use of physical punishment; some are based on views of the rights of children, some are based on the evidence for adverse psychosocial outcomes, and some on the role that physical punishment may play in the overall level of violence in a given society. Studies suggest that the use of physical punishment can be reduced through efforts to change normative parenting behaviors; parenting training seems capable of reducing the use of harsh punishment, and offers parents the opportunity to learn alternatives. There is evidence that parenting training can be delivered effectively in a variety of settings.
Does routine prophylaxis with caffeine prevent bronchopulmonary dysplasia in extremely low birth weight infants

Objective: The objective of the study was to determine the risk of developing bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants with and without caffeine prophylaxis. We hypothesized that there would be no difference in the risk of BPD between the two groups. Study Design: This was a comparative, single-center, retrospective cohort study comparing risk of BPD in ELBW infants (≤28-week gestation or ≤1001 g if gestational age [GA] unknown) receiving caffeine for BPD prophylaxis within the first 24 h of life to those with no prophylaxis. Materials and Methods: The risk of developing BPD in infants receiving caffeine for BPD prophylaxis was compared with a matched nonprophylaxis group. BPD was defined as the need for oxygen support at 36-week corrected GA (CGA). Secondary outcomes included total caffeine exposure, average weekly maintenance dose, and length of treatment and duration of mechanical ventilation. Results: One hundred and eight out of 153 infants (71%) received caffeine prophylaxis. The risk of developing BPD at 34–36-week CGA was not significantly different between the two groups (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.45–1.84). Infants in the prophylaxis group had higher total caffeine exposure and daily caffeine dose. There was no association between a patient's average daily dose of caffeine and risk of BPD (OR = 1.03, 95% CI: 0.91–1.18;P = 0.62). The duration of caffeine treatment was longer in the nonprophylaxis group. Infants in the prophylaxis group spent fewer days on mechanical ventilator (P = 0.03). Conclusion: The risk of BPD in infants receiving caffeine prophylaxis for BPD prevention was similar to a matched group of infants with no caffeine prophylaxis.
Research 'with' not 'on', yes, but with whom and how?

My starting point for this discussion is where we left the topic in an editorial 12 months ago; that is, the need for more ‘Public involvement in the production, dissemination and implementation of injury prevention research.’1 In this issue, Jennifer Woody Collins presents an informed critique of the challenges involved, and provides an elegant response.2 I commend her practical advice for researchers and practitioners to you for your consideration. The case for coproduced research is no longer contentious.3 Both for reasons of equity and justice, and for improved translation of research to public benefit, the compelling argument for coproduced research has been made. It is now our responsibility as editors and authors to apply the principle of coproduction in a way that fits our context and achieves the principle’s ethical and practical goals. From January 2020 all authors submitting manuscripts to Injury Prevention will be asked to consider …
Cracking mechanisms in asphalt mixtures

Results of recent experiments, advanced modeling efforts, and field performance evaluation were compared to fundamental assumptions associated with traditional fatigue and critical condition approaches. Findings revealed that the critical condition approach most accurately represents the actual mechanisms of pavement cracking. A top-down cracking (TDC) performance prediction model developed based on the hot mix asphalt-fracture mechanics (HMA-FM) was employed to illustrate the full potential of the critical condition approach. The work presented supports serious consideration of a paradigm shift from the traditional fatigue approach to the critical condition approach. Such a shift should enhance understanding of mechanisms and lead to more effective material specifications and pavement design systems.
Jehovah's Witness Patients “Going the Extra Mile” for Bloodless LVAD Implantation

Purpose Due to their religious beliefs, Jehovah's Witnesses (JWs) do not accept blood products; consequently, these patients with end-stage heart failure frequently seek a center willing to perform bloodless left ventricular assist device (LVAD) implantation. We assessed the challenges JWs confront in obtaining access to care, based on our center's experience orchestrating bloodless LVAD implantation. Methods We retrospectively reviewed the medical records of 36 patients - 18 JWs and 18 non-JWs - undergoing LVAD implantation at our center. Results Our findings revealed that JWs travelled a significantly greater distance to receive treatment than non-JWs (median: 293 (107.75, 667.5) vs 32.5 miles (15.3, 74.5), P = 0.006). Pre-operative characteristics, including INTERMACS profiles and re-operative status at implant, were comparable between the two groups (P > 0.05 for all). However, all JWs underwent concomitant surgeries at the time of bloodless LVAD implantation, as compared to 67% of non-JWs (P = 0.019). Length of stay, discharge location, and peri-operative outcomes were not significantly different (P > 0.05). We found that JWs currently face barriers in the availability, appropriateness, preference, and timeliness of access to care (Figure 2). In particular, being refused implantation at centers nearer to their residence causes JWs to travel excessive distances in hopes of treatment; however, long-distance travel may prolong the time until treatment and may not be an option for patients with financial or logistical challenges. Conclusion Our center's experience has shown that JWs face unnecessary barriers in access to care, but they can be successfully operated on with the use of optimization protocols and open communication between the patient and care team. Further research is needed to elucidate the challenges JWs face in accessing care and identify potential solutions which balance ethical considerations with patient autonomy.
Metastatic Renal Cell Carcinoma to the Spine: Outcomes and Morbidity: Single-Center Experience.

Background Renal cell carcinoma with metastases to the spine (RCCMS) requires a multidisciplinary approach. We reviewed our institutional experience with RCCMS patients undergoing spinal surgery in order to identify factors that may affect clinical outcomes, survival, and complications. Methods Patients with RCCMS who underwent operative intervention from 2007 to 2020 were reviewed retrospectively. Results Forty-four patients with the diagnosis of RCCMS were identified. Pain was the most common symptom, and neurologic dysfunction was present in one third of cases. Thoracic spine was the most common location (N = 27), followed by the lumbar (N = 12) and cervical (N = 5) regions. The overall survival from diagnosis of renal cell carcinoma was 25 (2 − 194) months and 8 (0.3 − 92) months after spinal surgery. Gender, age, spinal level, postoperative radiation, and nephrectomy had no bearing on survival. Survival for patients with a Tokuhashi score of 0 − 8, 9 − 11, and 12 − 15 was 6.5 (1.5 − 23.5), 8.9 (0.3 − 91.6), and 23.4 (2.5 − 66) months, respectively (P = 0.03). The postoperative American Spinal Cord Injury Association score of E (hazard ratio 0.109 [95% confidence interval 0.022 − 0.534, P = 0.006) also bore a significant influence on survival. There was a total of 10 complications in 7 of 44 (16%) patients. Conclusions Median postoperative survival of patients with RCCMS was 8 (0.3 − 92) months. Higher Tokuhashi score and ASIA E score at follow-up correlated with improved overall survival. Complication rate was 16%. Spinal surgery in RCCMS is indicated for the preservation of function and prevention of neurologic deterioration. Multimodality therapy with improved chemotherapy and stereotactic spinal radiation is expected to impact quality and length of survival positively.
Quantitative Analysis of Multiparty Tariff Negotiations

We develop a model of international tariff negotiations to study the design of the institutional rules of the GATT/WTO. A key principle of the GATT/WTO is its most‐favored‐nation (MFN) requirement of nondiscrimination, a principle that has long been criticized for inviting free‐riding behavior. We embed a multisector model of international trade into a model of interconnected bilateral negotiations over tariffs and assess the value of the MFN principle. Using 1990 trade flows and tariff outcomes from the Uruguay Round of GATT/WTO negotiations, we estimate the model and use it to simulate what would happen if the MFN requirement were abandoned and countries negotiated over discriminatory tariffs. We find that if tariff bargaining in the Uruguay Round had proceeded without the MFN requirement, it would have wiped out the world real income gains that MFN tariff bargaining in the Uruguay Round produced and would have instead led to a small reduction in world real income relative to the 1990 status quo.
Basic Definitions and Concepts

Most of the terminology used in this book is standard and in common use in the synthesis community [54, 13, 14]. This chapter is devoted to the definition of the nontrivial terminology and an elucidation of some of the basic concepts.
The General Structure of Decentralization in Mali and Ghana

The decentralization process launched in the 1990’s by African countries has changed, at least on the surface, the structure of governance in many countries in the region. Countries as diverse as South Africa, Nigeria, Senegal, Mali, Burkina Faso, Benin and Cote d’Ivoire have either completed or made considerable progress in the implementation of the transfer of powers to local levels. In all of these countries, important changes were made to the constitution in order to provide a legal basis for the process. Decentralization has therefore adopted different forms in different countries.
Mitigation options for carbon dioxide emissions from buildings: A global analysis

Abstract Between 1971 and 1992, growth in carbon dioxide (CO 2 ) emissions from buildings varied widely by region, ranging from 0.9% per year in the industrialized countries to 0.7% per year in Eastern Europe and the former Soviet Union and 5.9% per year in developing countries. This paper outlines energy efficiency improvements for buildings and the overall technical potential to reduce CO 2 emissions by cutting growth in energy consumption in buildings. Three scenarios of future buildings CO 2 emissions in 2020 were developed. Under the business as usual scenario, buildings emissions increase 90% over 1990 levels. A scenario that involves adopting more efficient energy using practices and technologies is estimated to produce CO 2 emissions 50% above 1990 levels. A scenario with powerful incentives for energy efficiency could lead to CO 2 emissions 28% above 1990 levels. Much of the CO 2 growth is the result of population growth and growth in energy services, especially in developing countries. Policy instruments to reduce energy use and related CO 2 emissions include real increases in energy prices, aggressive use of energy efficiency policies, major programs to transfer knowledge, technology, and tools for transforming markets to the developing world and continued efforts to pursue research and development in technologies and practices to increase energy efficiency in buildings.
Some assembly required: building a digital government for the 21st century

This material is based upon work supported in part by the National Science Foundation under Grant No. 99-181. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.
Rewards and Intrinsic Interest

It is usually assumed that giving rewards for performing a task increases future motivation for and engagement in that activity. A large body of research supports this assumption (Baldwin & Baldwin, 1998; Sarafino, 2001). In the early 1970s, however, studies began to find that under certain conditions, the opposite effect seemed to occur: External rewards for performing an intrinsically interesting activity undermined subsequent interest in and performance of that task. Keywords: interest; intrinsic interest; motivation; rewards
Theoretical Foundations of Learning Communities

This chapter describes the historical and contemporary theoretical underpinnings of learning communities and argues that there is a need for more complex models in conceptualizing and assessing their effectiveness.
2‐Cyanoethylphosphoric Acid

[2212-88-6] C3H6O4NP (MW 151.06) InChI = 1S/C3H6NO4P/c4-2-1-3-8-9(5,6)7/h1,3H2,(H2,5,6,7) InChIKey = NJDPBWLDVFCXNP-UHFFFAOYSA-N (used in the synthesis of phosphoric acid esters of carbohydrates, nucleosides, nucleotides, and other molecules) Physical Data: mp 165 °C;1 IR: 2500, 2210, 1623, 1548 cm−1;1 1H NMR (CF3CO2H): δ 5.64 (dt, 2H, J = 5.5, 6.5 Hz), 7.12 (t, 2H, J = 5.5 Hz);2 31P NMR: δ 1.2 (JPH = 725 Hz).3 Form Supplied in: as barium salt. Handling, Storage, and Precautions: a stock solution of 2-cyanoethylphosphoric acid is prepared by dissolving an exact quantity of the barium salt in water and by passage of this solution through a column of Dowex-50W (H+ form). The eluate is evaporated in vacuo resulting in a thick syrup that is dried by addition and evaporation of pyridine. The resulting residue is dissolved in pyridine and the solution is transferred (using pyridine washes) to a volumetric flask and diluted with pyridine to give a final concentration of 1.0 mmol/mL.1
Antitumor agent cabozantinib decreases RANKL expression in osteoblastic cells and inhibits osteoclastogenesis and PTHrP-stimulated bone resorption.

Cabozantinib, an inhibitor of vascular endothelial growth factor and hepatocyte growth factor signaling, decreases bone lesions in patients with prostate cancer. To determine direct effects of cabozantinib on bone, resorption in neonatal mouse bone organ culture and on gene expression, proliferation, and phenotypic markers in osteoblast and osteoclast cell lines were examined. Cabozantinib, 0.3 and 3 µM, prevented PTHrP-stimulated calcium release from neonatal mouse calvaria. Since the effect on resorption could reflect effects on osteoblasts to prevent osteoclast activation, or direct inhibition of osteoclasts, responses in osteoblastic and osteoclast precursor cell lines were examined. Twenty-four-hour treatment of osteoblastic MC3T3-E1 cells with 3 µM cabozantinib decreased expression of receptor activator of NFkB ligand (RANKL) and alkaline phosphatase. Forty-eight-hour treatment of MC3T3-E1 cells with 3 µM cabozantinib inhibited cell proliferation and decreased MTT activity. Effects on alkaline phosphatase activity were biphasic, with small stimulatory effects at concentrations below 3 µM. When RAW 264.7 osteoclast precursor cells differentiated with 20 ng/ml RANKL were co-treated for 24 h with 3 µM cabozantinib, expression of RANK, TRAP, cathepsin K, alpha v or beta 3 integrin, or NFATc1 were unaffected. Five-day treatment of RANKL-treated RAW 264.7 cells with 3 µM cabozantinib decreased TRAP and MTT activity. The results suggest that the osteoblast could be the initial target, with subsequent direct and indirect effects on osteoclastogenesis leading to decreased resorption. The multiple effects of cabozantinib on the cell microenvironment of bone are consistent with its effectiveness in reducing lesions from prostate cancer metastases. J. Cell. Biochem. 115: 2033–2038, 2014. © 2014 Wiley Periodicals, Inc.
Leonid Storm Flux Analysis From One Leonid MAC Video AL50R

A detailed meteor flux analysis is presented of a seventeen-minute portion of one videotape, collected on November 18, 1999, during the Leonid Multi-instrument Aircraft Campaign. The data was mottled around the peak of the Leonid meteor storm using an intensified CCD camera pointed towards the low southern horizon. Positions of meteors on the sky were measured. These measured meteor distributions were compared to a Monte Carlo simulation, which is a new approach to parameter estimation for mass ratio and flux. Comparison of simulated flux versus observed flux levels, seen between 1:50:00 and 2:06:41 UT, indicate a magnitude population index of r = 1.8 ± 0.1 and mass ratio of s = 1.64 ± 0.06. The average spatial density of the material contributing to the Leonid storm peak is measured at 0.82 ± 0.19 particles per square kilometer per hour for particles of at least absolute visual magnitude +6.5. Clustering analysis of the arrival times of Leonids impacting the earth’s atmosphere over the total observing interval shows no enhancement or clumping down to time scales of the video frame rate. This indicates a uniformly random temporal distribution of particles in the stream encountered during the 1999 epoch. Based on the observed distribution of meteors on the sky and the model distribution, recommendations are made for the optimal pointing directions for video camera meteor counts during future ground and airborne missions.
Measurement-Based Analysis of Error Latency

This paper demonstrates a practical methodology for the study of error latency under a real workload. The method is illustrated with sampled data on the physical memory activity, gathered by hardware instrumentation on a VAX 11/780 during the normal workload cycle of the installation. These data are used to simulate fault occurrence and to reconstruct the error discovery process in the system. The technique provides a means to study the system under different workloads and for multiple days. An approach to determine the percentage of undiscovered errors is also developed and a verification of the entire methodology is performed. This study finds that the mean error latency, in the memory containing the operating system, varies by a factor of 10 to 1 (in hours) between the low and high workloads. It is found that of all errors occurring within a day, 70 percent are detected in the same day, 82 percent within the following day, and 91 percent within the third day. The increase in failure rate due to latency is not so much a function of remaining errors but is dependent on whether or not there is a latent error.
Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.
Monolithic integration of the vertical IGBT and intelligent protection circuits

In this paper, we have developed a new smart discrete technology to monolithically integrate the high voltage vertical IGBT with low-voltage NMOS protection circuitry by adding a p-well step to the conventional IGBT process. Two new 600 V intelligent IGBTs, based on the same technology but using different protection schemes, are reported for the first time. The first intelligent IGBT provides protection against over-current and over-temperature conditions. The second intelligent IGBT provides protection against short circuit conditions by means of sensing collector voltage. The typically observed characteristics of the intelligent IGBT's include a forward voltage of 1.4 V at a current density of 100 A/cm/sup 2/, a turn-off fall time of 200 ns, and a short-circuit withstand time at 125/spl deg/C of more than 50 /spl mu/s.
A progressive nurse practitioner student evaluation tool

Abstract Purpose: To describe the process of designing a new progressive nurse practitioner student clinical evaluation tool based on competencies. Data sources: Selected research articles and professional organization published guidelines. Conclusions: Evaluation of nurse practitioner students' clinical performance is an important and often complex responsibility of faculty. The clinical evaluation tool should reflect the changing expectations associated with particular courses across the curriculum and be based on the competencies identified by the National Organization of Nurse Practitioner Faculties. Collaboration by faculty is the key to development of an accurate and useful clinical evaluation tool. Implications for practice: The progressive nurse practitioner clinical evaluation tool presented here is the result of integrating specific clinical course outcomes and competencies recognized by key nurse practitioner associations.
COMPOSITION AND SENSORY ATTRIBUTES OF BACON AS INFLUENCED BY A BETA‐AGONIST‐674,239 TREATMENT AND SEX1

Uncooked and cooked bacon from control and beta-agonist L-674,239 fed female (gilt) and male castrate (barrow) pigs were evaluated by chemical and sensory analyses. No differences were observed in processing parameters or cook yields of bacon due to beta-agonist treatment or sex of animal. Uncooked bacon from beta-agonist fed pigs compared to controls, and from gilts compared to barrows, contained more protein, less fat and was scored higher for lean:fat ratio. The cooked bacon from gilts had more visual lean, greater perceived crispness and coated the mouth less than the bacon from barrows. Cholesterol in cooked bacon did not differ due to beta-agonist treatment but was higher in gilts than in barrows.
Cytotoxicity of non-myofilament-incorporated troponin T fragments

Troponin T (TnT) is a striated muscle-specific protein and an abundant component in skeletal and cardiac myofilaments. Forced expression of TnT protein in non-muscle cells or undifferentiated myoblasts in the absence of myofibrils indicated cytotoxicity (Wang et al., J. Biol. Chem. 280:13241-9, 2005). To investigate the cytotoxic effect of non-myofibril-incorporated TnT, we constructed non-fusion co-expression vectors encoding green fluorescence protein tracer and different regions of the TnT polypeptide chain. Transient transfection in culture was studied in HEK293 non-muscle cells and undifferentiated C2C12 myoblasts. Cytotoxicity of the TnT fragments was examined by the viability of the transfected cells. The results revealed distinct toxic effects of different regions of TnT. The evolutionarily conserved middle and C-terminal segments of TnT were highly toxic to cells whereas the N-terminal variable region was not. The cytotoxicity of the middle and C-terminal regions of TnT was associated with apoptotic cell death. Although muscle cells have high capacity of proteolysis to rapidly remove non-myofilament incorporated TnT protein, peak releases of TnT or TnT fragments from myofibrils may occur in the events of myocardial ischemia reperfusion and skeletal muscle fatigue or injuries. When the level of non-myofilament-associated TnT and TnT fragments exceeds the protective capacity of proteolytic removal in the muscle cell, they may impose cytotoxic effect and cause cell death. Therefore, the activity of non-myofilament-associated TnT or TnT fragments in inducing apoptosis and cell death is a potential pathogenic factor, particularly important in adult cardiac myocytes that lack the ability of regeneration.
Presynaptic adenosine A1 receptors regulate retinohypothalamic neurotransmission in the hamster suprachiasmatic nucleus

Adenosine has been implicated as a modulator of retinohypothalamic neurotransmission in the suprachiasmatic nucleus (SCN), the seat of the light-entrainable circadian clock in mammals. Intracellular recordings were made from SCN neurons in slices of hamster hypothalamus using the in situ whole-cell patch clamp method. A monosynaptic, glutamatergic, excitatory postsynaptic current (EPSC) was evoked by stimulation of the optic nerve. The EPSC was blocked by bath application of the adenosine A1 receptor agonist cyclohexyladenosine (CHA) in a dose-dependent manner with a half-maximal concentration of 1.7 µM. The block of EPSC amplitude by CHA was antagonized by concurrent application of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The adenosine A2A receptor agonist {"type":"entrez-protein","attrs":{"text":"CGS21680","term_id":"878113053","term_text":"CGS21680"}}CGS21680 was ineffective in attenuating the EPSC at concentrations up to 50 µM. Trains of four consecutive stimuli at 25 ms intervals usually depressed the EPSC amplitude. However, after application of CHA, consecutive responses displayed facilitation of EPSC amplitude. The induction of facilitation by CHA suggested a presynaptic mechanism of action. After application of CHA, the frequency of spontaneous EPSCs declined substantially, while their amplitude distribution was unchanged or slightly reduced, again suggesting a mainly presynaptic site of action for CHA. Application of glutamate by brief pressure ejection evoked a long-lasting inward current that was unaffected by CHA at concentrations sufficient to reduce the evoked EPSC amplitude substantially (1 to 5 µM), suggesting that postsynaptic glutamate receptor-gated currents were unaffected by the drug. Taken together, these observations indicate that CHA inhibits optic nerve-evoked EPSCs in SCN neurons by a predominantly presynaptic mechanism.
Acid deposition-precursor emission relationship in the northeastern U.S.A.: The effectiveness of regional emission reduction

Abstract About 20% of each of the emitted SO2 and NOx are wet-deposited as sulfate and nitrate ions over the northeastern U.S.A. This leads to a mean regional precipitation acidity of 67 μmol l−1 (pH = 4.2), in good agreement with observation. Assuming a constant emission/deposition ratio, the average rain acidity can be predicted for various emission reduction scenarios.
Adsorption and surface reaction rates from dynamic data for single catalyst particles

Analyse de donnees dynamiques par la methode des moments. Pour une simple particule de catalyseur, on donne les equations du moment dans trois cas: traceur non adsorbant; adsorption reversible; adsorption reversible et reaction de surface
Extra (non-contingent) food does not affect behavioral tolerance to d-amphetamine's rate-decreasing effects

Tolerance refers to the diminished effect of a drug following its repeated administration such that a larger dose is needed to obtain the initial effect. Tolerance to a drug's effects on operant behavior is more likely to develop when initial drug administration results in a loss of reinforcement. It remains unknown how offsetting loss of reinforcement influences the development of tolerance. Providing extra (non-contingent) food pellets was hypothesized to impede the development of tolerance to effects of a repeatedly administered dose of d-amphetamine that reduced the number of food pellets earned by rats. A multiple schedule with two variable-interval (VI) 60-s components resulting in food delivery was used to maintain lever pressing. Extra food pellets were provided in one of those components according to a variable-time (VT) 120-s or a VT 30-s schedule for separate groups of rats (n=6 for each group). Effects of d-amphetamine (0.1-3.0mg/kg) were tested before (acute) and during (chronic) injections (45days) of an individually selected, repeatedly administered dose that reduced the number of food pellets earned by at least 50% compared to when saline was tested acutely. There was a dose-dependent decrease in lever-press rates and food pellets earned. The development of tolerance was quantified by dividing the area-under-the-curve (AUC) of the chronic dose-effect function by the AUC of the acute dose-effect function. Tolerance developed to a similar extent in components with and without extra food pellets for rats in both groups. These results indicate that offsetting reinforcement loss, at least as studied here, did not differentially affect tolerance development.
Detection of monolayer gratings of adsorbates by linear optical diffractions

We report the detection of linear optical diffraction of a He-Ne laser probe beam from a monolayer grating of molecular adsorbates up to the fifth order with no electronic or electromagnetic enhancement. The advantages of using linear diffraction to probe surface diffusion of adsorbates are discussed.
Effect of the Chemosterilant P, P' Bis(1-aziridinyl)-N-(3-methoxypropyl)-phosphinothioic Acid on Ribosomal RNA and Ribosomal Protein in the Eggs of House Flies

In the eggs of Musca domestica L. chemosterilized by P, P '-bis (1-aziridinyl)-N-(3-methoxypropyl) phosphinothioic acid, the nucleotide ratios of the ribosomal ribonucleic add (rRNA) appeared normal, and there was some synthesis of ribosomes, rRNA, and ribosomal protein. However the maxima of the UV spectra of the ribosomes and rRNA from chemosterilized eggs differed from the maxima found for ribosomes and rRNA from normal eggs. For normal eggs the UV maxima were at 267 mµ, for ribosomes and 263 mµ, for rRNA; for chemosterilized eggs they were at 271 mµ for ribosomes and 257 mµ, for rRNA. There was also an abnormal increase in hyperchromicity of the ribosomes from chemosterilized eggs after treatment with ribonuclease.
Crystallization of Silver Stearate from Sodium Stearate Dispersions

Silver carboxylates, the common silver source used for photothermographic imaging materials, are normally obtained from the reaction between sodium soap (e.g., sodium stearate) and silver nitrate. They form platelet-like crystals with a lamellar structure in water at room temperature. Light microscopy investigations reveal that the formation of silver stearate (AgSt) crystals follows a diffusion-controlled mechanism. The reaction between the sodium soap and silver nitrate preferentially occurs in solution rather than on the soap fiber solid interface. Cryogenic transmission electron microscopy, together with an on-the-grid reaction technique, provides a useful tool to directly image silver stearate microstructures at the initial stages of AgSt precipitation. The AgSt reaction product first forms particles about 5 nm in size, which is similar to the d-spacing of final AgSt crystals. Those particles aggregate to produce larger and loosely packed embryonic crystals, the precursors to the ultimate silver stearate crystals.
Distinct roles of IL-7 and stem cell factor in the OP9-DL1 T-cell differentiation culture system.

Objective The OP9-DL1 culture system is an in vitro model for T-cell development in which activation of the Notch pathway by Delta-like 1 promotes differentiation of mature T cells from progenitors. The roles of specific cytokines in this culture system have not been well defined, and controversy regarding the role of IL-7 has recently emerged. We examined the roles played by IL-7, Flt3 ligand, and stem cell factor (SCF) in differentiation of adult bone marrow cells in the OP9-DL1 culture system. Methods Hematopoietic progenitor cells isolated from mouse bone marrow were cultured with OP9 or OP9-DL1 stromal cells and evaluated for T and B lymphocyte differentiation using immunofluorescent staining. Results IL-7 provided both survival/proliferation and differentiation signals in a dose-dependent manner. T-cell development from the CD4/CD8 double-negative (DN) stage to the CD4/CD8 double-positive (DP) stage required IL-7 provided by the stromal cells, while differentiation from the DP to the CD8 single-positive (SP) stage required addition of exogenous IL-7. SCF favored the proliferation of DN lymphoid progenitors and inhibited differentiation to the DP stage in a dose-dependent manner. Conversely, blocking the function of SCF expressed endogenously by OP9-DL1 cells inhibited proliferation of lymphoid progenitors and accelerated T-lineage differentiation. Flt3 ligand promoted proliferation without affecting differentiation. Conclusion These results validate the OP9-DL1 model for the analysis of T-cell development from bone marrow–derived progenitor cells, and demonstrate specific roles of SCF, IL-7, and Flt3L in promoting efficient T-lineage differentiation.
The European-Asian Trade of the Seventeenth Century and the Modernization of Commercial Capitalism

The emergence of modern capitalism in Europe between the fifteenth and eighteenth centuries has been a major topic of historical research and interpretation for many years. Among the current generation of historians there has been an ex,-plosion of interest in the relationship between the growth of capitalism and the expansion of Europe in the early modern era. The interpretive work of Wallerstein and Braudel and the detailed research of a host of others have added immensely to our knowledge of this relationship. They have led many historians to break away from the conceptual frameworks traditionally employed to explain both pre-industrial capitalism and European expansion.