cssi/SciSciGPT-SciSciNet huggingface dataset:
The Contribution of Salt Fingers to Vertical Mixing in the North Atlantic Tracer Release Experiment

Abstract The North Atlantic Tracer Release Experiment (NATRE) was performed in an area moderately favorable to salt fingers. However, the classic finger signature of a distinct thermohaline staircase caused by upgradient density flux was absent. This is likely because mixing by turbulence was sufficiently strong to disrupt the formation of permanent step and layer systems. Despite the lack of a staircase, optical shadowgraph profiles revealed that small-scale tilted laminae, previously observed in a salt-finger staircase, were abundant at the NATRE site. Using microstructure observations, the strength of salt-finger mixing has been diagnosed using a nondimensional parameter related to the ratio of the diffusivities for heat and buoyancy (Γ, “the dissipation ratio”). By examining the dissipation ratio in a parameter space of density ratio (Rρ) and Richardson number (Ri), the signal of salt fingers was discerned even under conditions where turbulent mixing also occurred. While the model for turbulence descr...
Principles of Pain Management

Upon completion of the chapter, the student will be able to: 1. Understand the pathophysiology of pain. 2. Know the steps on how to obtain an adequate pain history. 3. Identify the different types of medications used for treating pain, and their indications and limitations. 4. Appreciate that pain is multifactorial and often requires multiple modalities of treatment for improvement.
Smart Coordination Approach for Power Management and Loss Minimization in Distribution Networks with PEV Penetration Based on Real Time Pricing

The impact of Plug in Electric Vehicles (PEV) will be most significantly felt by the electric power distribution networks, and specifically by distribution transformers that exist on each neighborhood block and cul-de-sac as customers charge their PEVs. That impact is unlikely to be positive. Since PEV adoption is initially expected to cluster in neighborhoods where demand for PEVs is strongest, the new load may overload transformers, sap much-needed distribution capacity and also increase distribution network losses. Hence, the national goal of putting one million PEVs on the road by 2015 could easily impose a severe burden on the distribution network. Whether PEVs will help or hinder electricity provision will depend on how frequently and at what times the customers charge their vehicles. This behavior will be driven in part by the rate structures that are offered by utilities, as well as the price responsiveness of PEV owners to those rate structures. In this chapter, we propose a method to optimally charge the PEVs in order to minimize the system distribution network losses and to maximize energy transferred to PEVs. A novel short term prediction unit consisting of a receding time horizon method is proposed to forecast the PEV load and a multi objective bacterial foraging algorithm is used as an optimization tool. Also it is interesting to study the manner in which distribution network losses vary with PEV charging behavior. Hence the purpose of this chapter is to demonstrate a power management strategy using smart coordination approach to (a) design a charging and discharging infrastructure for the PEVs that maximizes energy delivered to PEV batteries and (b) reduce the distribution network losses to avoid overloading of the grid.
Unitary Symmetry of Strong Interactions

We have become accustomed to the fact that theories in elementary- particle physics change with the season or the year, as women’s fashions or new car models. Therefore, if a theory, or model, survives for longer than one or two years, one tends to become suspicious that either the theory really contains a grain of truth or — and this may well be the case with SU(3) symmetry — that the observed agreement between a model and experiment is in fact to some degree independent of the model and more a result of an accident of the dynamics of the problem.
Gender Matters in Biological Research and Medical Practice.

The t(11;22)(q24;q12) translocation is present in up to 95% of cases of Ewing’s sarcoma and results in the formation of an EWS-FLI1 fusion gene which encodes a chimeric transcription factor. The proximate role of EWS-FLI1 in the pathogenesis of Ewing’s sarcoma is thought to involve the activation of as yet largely unknown target genes. Many alternative forms of EWS-FLI1 exist because of variations in the locations of the EWS and FLI1 genomic breakpoints. The most common form, designated “type 1,” consists of the first seven exons of EWS joined to exons 6–9 of FLI1 and accounts for approximately 60% of cases. The “type 2” EWS-FLI1 fusion also includes FLI1 exon 5 and is present in another 25%. We and others have observed previously that the type 1 fusion is associated with a significantly better prognosis than the other fusion types. Because EWS-FLI1 is an aberrant transcription factor, we investigated whether these differences in clinical behavior may be correlated to functional differences by comparing transactivation by the type 1 EWS-FLI1 with other types in both heterologous cells (HeLa, NIH3T3) and homologous cells (Ewing’s sarcoma cell lines). In a panel of seven Ewing’s sarcoma cell lines, we found transactivation of a transiently transfected FLI1-responsive reporter construct to be significantly lower in cell lines with the type 1 fusion than in cell lines with the type 2 fusion (P = 0.003). Cotransfection of the same reporter construct with each of a series of seven EWS-FLI1 expression constructs (corresponding to the two major fusion types and five less common types) also showed that type 1 EWS-FLI1 was a significantly weaker transactivator than the type 2 product in both HeLa and NIH3T3 cells (P = 0.003, and P = 0.033, respectively). Electromobility shift assays showed equivalent binding of the type 1 and type 2 EWS-FLI1 to the consensus FLI1-responsive binding site, indicating that differences in transactivation were not due simply to differences in DNA binding affinity. The finding that the type 1 EWS-FLI1 fusion, associated with less aggressive clinical behavior, encodes a less active chimeric transcription factor may provide the basis for a molecular explanation of clinical heterogeneity in Ewing’s sarcoma.
IRA Withdrawals in 2013 and Longitudinal Results 2010-2013

The Employee Benefit Research Institute (EBRI) developed the EBRI IRA Database, which includes a wealth of data both by calendar year and longitudinally on IRAs, including withdrawals or distributions, allowing for the examination of IRA asset holdings both at a point in time and as the individual ages and either changes jobs or retires. The EBRI IRA Database is an ongoing project that collects data from multiple IRA-plan administrators. For year-end 2013, it contains information on 25.8 million accounts owned by 20.6 million unique individuals, with total assets of $2.46 trillion. This paper examines the percentage of Traditional- and Roth-IRA owners in the EBRI IRA Database that made a withdrawal in 2013. In this study on withdrawals, only those individuals owning either Traditional or Roth IRAs in the database are examined, a total of 16.9 million individuals with $2.14 trillion in assets. In addition, the amount and the proportion of the account this withdrawal represents are investigated, by IRA type and account balance, as well as by the gender and age of the account owner. Furthermore, this withdrawal activity is examined longitudinally over the years 2010-2013, with a particular focus on owners ages 70 or older (the point at which IRA rules on required minimum distributions become effective) in 2010. Just over 22 percent of individuals who owned a Traditional or Roth IRA took a withdrawal in 2013. The overall IRA withdrawal percentage was largely driven by activity among individuals ages 70-1/2 or older owning a Traditional IRA -- the group required to make withdrawals under federal required minimum distribution (RMD) rules for IRA owners beyond that age. In contrast, among individuals under age 60, 10 percent or fewer had a withdrawal. For those at the RMD age, the withdrawal rates at the median appeared close to the amount that was required to be withdrawn, though some were significantly more. For instance, looking at the consistent sample in the EBRI IRA Database, approximately 25 percent of those 71 or older took a withdrawal amount in excess of that required by law for Traditional IRAs. Among those ages 70 or older, withdrawal rates over a four-year period showed that most individuals were withdrawing at a rate that was likely to be able to sustain some level of post-retirement income from IRAs as the individual continued to age. Further study is needed to see if these individuals are maintaining those withdrawal rates over longer periods of time.The PDF for the above title, published in the July 2015 issue of EBRI Notes, also contains the full text of another July 2015 EBRI Notes article abstracted on SSRN: “Satisfaction With Health Coverage and Care: Findings from the 2014 EBRI/Greenwald & Associates Consumer Engagement in Health Care Survey.”
Early Radiosurgery Improves Hearing Preservation in Vestibular Schwannoma Patients With Normal Hearing at the Time of Diagnosis

Purpose Vestibular schwannomas (VS) are increasingly diagnosed in patients with normal hearing because of advances in magnetic resonance imaging. We sought to evaluate whether stereotactic radiosurgery (SRS) performed earlier after diagnosis improved long-term hearing preservation in this population. Methods and Materials We queried our quality assessment registry and found the records of 1134 acoustic neuroma patients who underwent SRS during a 15-year period (1997-2011). We identified 88 patients who had VS but normal hearing with no subjective hearing loss at the time of diagnosis. All patients were Gardner-Robertson (GR) class I at the time of SRS. Fifty-seven patients underwent early (≤2 years from diagnosis) SRS and 31 patients underwent late (>2 years after diagnosis) SRS. At a median follow-up time of 75 months, we evaluated patient outcomes. Results Tumor control rates (decreased or stable in size) were similar in the early (95%) and late (90%) treatment groups ( P =.73). Patients in the early treatment group retained serviceable (GR class I/II) hearing and normal (GR class I) hearing longer than did patients in the late treatment group (serviceable hearing, P =.006; normal hearing, P Conclusions SRS within 2 years after diagnosis of VS in normal hearing patients resulted in improved retention of all hearing measures compared with later SRS.
Fabrication of thermally-conductive carbon nanotubes-copper oxide heterostructures

A complete dry processing route is developed for the fabrication of thermally-conductive carbon nanotube (CNT)-copper oxide (CuOx) heterostructures. This was achieved by the deposition of copper (Cu) onto CNTs and subsequent annealing in Ar and air environment to convert the coated Cu into CuOx nanoparticles. The survivability and diameters of CNTs were studied to ensure their integrity after the multiple processing steps and annealing temperatures (400 °C). The as-produced CNTs, air/Ar-annealed CNTs, Cu-coated CNTs, and CNT-CuOx heterostructures were characterized to study their structure, phase, and morphology using microscopy, elemental analysis, X-ray diffraction, and sheet resistance. It was observed that CNTs could survive the processing conditions and became coated with CuOx nanoparticles. The sheet resistance of CNTs coated with CuOx nanoparticles was ∼4 times greater than the as-produced CNTs. The Raman spectroscopy-based estimation of thermal conductivity of CNTs and CNT-CuOx heterostructures showed 2-7 times enhancement for the latter as compared to pure CuOx. In conclusion, such hybrid CNT-based heterostructures are promising for applications in thermal management.
C. Wright Mills: A Native Radical and His American Intellectual Roots

(1985). C. Wright Mills: A Native Radical and His American Intellectual Roots. Journal of Economic Issues: Vol. 19, No. 3, pp. 849-860.
Strange and stringy.

The author discusses states of matter other than solids, liquids, and gases that arise from transitions among electrons in materials that can be described in part by string theory and quantum physics. He describes the applicability of quantum entanglement in explaining the instantaneous anticorrelation communications that appear to occur between electrons. Topics include the theory of gravitation developed by the physicist Albert Einstein, crystal structures, superconductors, black holes, and collaboration between specialists in string theory and condensed matter. The impact of electron spin on barium iron arsenide is mentioned.
Synergistic numerical and experimental simulations to evaluate a surface probe to determine body core temperatures

ABSTRACTA highly accurate noninvasive means of determining body core temperature is proposed and characterized by synergistic use of numerical and experimental simulations. It was demonstrated that the new surface probe yields skin surface temperature measurements that are within a few tenths of a degree of the body core temperature. Advanced simulation techniques such as the Monte Carlo method for the determination of radiant heat losses were used to ensure high accuracy. Convective heat losses were also accounted. Full account was taken of the multilayer nature of the tissue bed beneath the skin surface, each layer with its specific thermophysical properties, blood perfusion, and metabolic heating. For the validation of the numerical simulation model, an experimental apparatus was fabricated and operated. The experimental data supported the numerical predictions. The capability of the probe to accurately follow thermal transients was the focus of a redesign, yielding small-fraction-of-a-minute following...
Feeding density influences acquisition of Borrelia burgdorferi in larval Ixodes scapularis (Acari: Ixodidae)

The intensity of Borrelia burgdorferi transmission in nature is dependent upon the efficiency of acquisition of spirochetes by larval Ixodes scapularis Say (= I. dammini Spielman, Clifford, Piesman & Corwin). White-footed mice infected with B. burgdorferi were infested weekly for 5 consecutive weeks with 25 or 250 larval I. scapularis. Prevalence of infection in nymphs derived from larvae fed at high density (25.0–38.9%) was consistently higher than in nymphs derived from larvae fed at low density (6.7–23.5%). Spirochete prevalence in nymphal I. scapularis populations in nature may be influenced by larval population density.
E-060 Effect of Packing Density and Coil Uniformity on Coil Permeability

Introduction Durability of coiling procedures varies widely, and a better understanding of coil dynamics may help improve the treatment strategy. The goal of this study is to evaluate how packing density (PD) and coil uniformity impact aneurysm occlusion efficiency, which is conceptually associated with coil mass permeability. Materials and methods Experimental A1 aneurysm models were coiled using Guglielmi detachable coils (GDC) or Target coils. Coiled aneurysms were connected to a flow system filled with 1 µm fluorescent microsphere solution. The coil permeability was defined as the ratio of the microspheres that passed through the coil mass to the microspheres that circulated in the parent vessel. One neck section and 2 dome sections were obtained from each aneurysm for image analysis, including surface area fraction (SAF) and uniformity measurements. SAF was defined as the ratio of coil mass cross-sectional area to aneurysm cross-sectional area, and uniformity was determined from fractal-based heterogeneity measure, lacunarity. Lacunarity values closer to 0 indicate a homogeneously distributed coil mass. A statistical model was used to predict coil mass permeability as the outcome, with packing and uniformity measures as predictor variables. If the packing and uniformity measures exhibited statistically significant correlation, then principal component regression analysis was used for statistical modeling. Results All aneurysm PDs fell within the range of 27.1% to 45.5%, with a mean PD of 34.3 ± 4.4%. Permeability varied as a function of spatial coil uniformity for a given packing density (36%, Figure 1). With a higher uniformity (lacunarity: 0.06 vs. 0.09), the Target coiled aneurysm allowed less microspheres through the coil mass, as compared to the GDC coiled aneurysm. The lacunarity measures showed that in general, the coil distribution at the cross section of the neck was less uniform than in the dome. Coil mass permeability was statistically correlated with PD, SAF of dome and lacunarity of dome. Principal component regression analysis identified a primary factor with similar weights for PD, SAF of dome, and lacunarity of dome (range: 0.55–0.61). Coil mass permeability was modeled better with principal component regression incorporating the above measures (r 2 = 0.7) than linear regression with PD alone (r 2 = 0.46). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures. Conclusion In addition to packing density, coil mass distribution has an important impact on excluding the aneurysm from the circulation. Disclosures J. Chueh: None. S. Vedantham: None. A. Puri: None. A. Wakhloo: 1; C; NIH, Philips Healthcare. 2; C; Stryker Neurovascular. M. Gounis: 1; C; eV3/Covidien, Philips Healthcare, NIH, Silk Road, Stryker Neurovascular. 2; C; fee-per-hour: Stryker Neurovascular, fee-per-hour: Codman Neurovascular.
The expulsion of Echinostoma trivolvis (Trematoda) from ICR mice: scanning electron microscopy of the worms.

Echinostoma trivolvis adults are rejected from ICR mice within 3 weeks postinfection (p.i.) but are retained in golden hamsters for >15 weeks. The present study used scanning electron microscopy (SEM) to examine worm topography in ICR mice, particularly that of the collar spines, and to correlate worm loss with tegumentary changes. The topography of the worm in ICR mice was similar to that observed in previous studies on this echinostome in domestic chick embryos, chickens, and golden hamsters. Observations were made on the pattern of collar spines in 115 worms from ICR mice at 3–14 days p.i. All worms examined at 3 days exhibited extended spines, whereas about 70% of the worms examined at 14 days displayed retracted or missing spines. Eight worms from golden hamsters examined at 14 days p.i. showed extended collar spines. The retraction or loss of collar spines may play a role in the expulsion ofE. trivolvis from ICR mice.
Evaluation on chemical pollutants and harmful factors of food in Bengbu city,2010-2011

Objective To know the state of chemical pollutants and harmful factors of food in Bengbu.Method Random sampling principle was adopted,and fixed monitoring networks were set up to investigate chemical pollutants and harmful factors of food in Bengbu's downtown and Hugou town of Guzhen county.Chemical pollutants such as heavy metal,aflatoxin M1,pesticide residues,food additive,sulfur dioxide,nitrite were detected.Results We monitored 15 kinds of foods with the number of samples amounting 602 in 2010~2011.They were summarized as follows: the qualified rate of lead,cadmium and mercury in food were 100.00%,96.65% and 95.83% respectively.The content of cadmium in pig kidney was high,with mean value of 0.760mg/kg.The detection rates of organophosphorus,organochlorine,pyrethroid in vegetables and edible fungus were 13.33%,1.66%,and 10.00%,which were in agreement with standard values.The aflatoxin M1 in both milk and dairy products was below detection limits.The saccharin sodium in roasted seeds and nuts,the sodium cyclamate in candied fruits,the benzoic acid in salted vegetables were over the standard value by 20.00%,70.0% and 50.00%,respectively.The aluminum in flour product was larger than the standard value by 55.50%.All pumpkin seeds were detected with sulfur dioxide residue,among which 80.00% surpassed the standard value.Conclusion The pollution extents in food arising from heavy metals,pesticide residues and aflatoxin M1 were relatively slight.There was a serious abuse of food additives in roasted seeds and nuts,candied fruit,salted vegetable.Use of bulking agent aluminum is more than the standard value,and so did the sulfur dioxide residue in pumpkin seeds due to bleaching.The relevant departments should enhance food supervision and technical guidance,emphasize was monitoring work in food additives among roasted seeds and nuts,candied fruits,salted vegetables and sulfur dioxide residues of pumpkin seeds.
Progress on the study of Chikungunya disease

基孔肯雅病是由基孔肯雅病毒(Chikungunya virus,CHIKV)感染所致.该病主要经蚊虫吸血传播,其主要临床表现为发热、关节剧烈疼痛、皮疹和轻度出血体征,称为"基孔肯雅热".人群对基孔肯雅热普遍易感,任何年龄均可感染发病,当基孔肯雅热初次暴发时,可使大量人群发病[1]。
E-062 transradial access for acute interventional stroke therapy

Introduction Mechanical thrombectomy for acute stroke therapy is the new standard of care. Interventionalists may encounter difficulty using femoral access such that another option is needed. Transradial access can be of a benefit in difficult cases. Such cases include, advanced age, anatomic variations such as a bovine arch, posterior circulation stroke, severe aortic arch unfolding, morbid obesity and severe femoral disease (leading to increased risks of transfemoral catheterization). We are reporting our single center experience with transradial access for acute ischemic stroke therapy. Methods and materials We retrospectively reviewed our stroke interventional database (January 2013–March 2015) for all patients who underwent endovascular mechanical thrombectomy for acute ischemic stroke using a transradial approach. We included all patients where primary or secondary transradial access was attempted to gain access to the intracranial circulation. The interventionalist performs a modified Allen’s test followed by micropuncture needle access and administration of a prophylactic cocktail of verapamil 5mg, heparin 1000 units, and nitroglycerin 200ug through the sheath. Under fluoroscopy, a 3mm J-wire is placed into the radial artery and advanced into the subclavian artery. A NeuronMax-088 sheath (©Penumbra, Irvine CA) is then inserted. A short 5F sheath is only used if wire advancement is difficult. Obstruction due to a loop or severe angulation can be resolved with road mapping, glide wire, diagnostic catheter and sheath exchange over an Amplatz wire. The sheath is advanced into the right subclavian and kept proximal to the vertebral origin. Depending on the target vessel there are several techniques available to engage the required vessel. Results We Identified 19 patients as having transradial access for thrombectomy following acute stroke. Patient ages ranged 40–92 years of age with a mean of 81.42 (±13.82). In patients with Primary attempts time from radial puncture to clot engagement ranged from 7–46 mins with a mean of 26.7 min (±13.1). In 16/19 patients successful catheterization of the target vessel was accomplished using the transradial approach. In 3 patients transradial axis was not successful due to tortuous anatomy, poor vessel caliber and upstream occlusion. Conclusion Transradial artery access for neuro-interventional procedures is rarely considered today. Our small case study suggests that transradial access is safe and efficacious in advance stroke therapy. Further studies with larger sample size are needed. Disclosures J. Farkas: None. K. Sivakumar: None. T. Sabharwal: None. H. Dababneh: None. A. Tiwari: None. K. Arcot: None.
Causal Realism and the Egocentric Predicament

It is my contention that a justified theory of how God grounds the physical universe must be based on a discussion of the nature of our knowledge of the physical universe. In this chapter and part of the next, I shall argue that a version of phenomenalism constitutes the best account of that knowledge; and then I shall conclude Chapter 8 with a defense of the thesis that God provides the ultimate explanation of the truth of a phenomenalist explanation of what physical things consist of.
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation

Chronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and upregulated genes associated with defense response and immune system processes. In adulthood the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity.
ANIMAL BITE INFECTIONS OF THE HAND

This article discusses a wide variety of animal bite wounds, from common dog and cat wounds to infections from more exotic creatures such as marine animals and snakes. Illustrations of the wound types inflicted by various animals are illustrated and a thorough description of proper treatment techniques is presented.
Progression and Transmission of HIV/AIDS (PATH 2.0).

Background. HIV transmission is the result of complex dynamics in the risk behaviors, partnership choices, disease stage and position along the HIV care continuum—individual characteristics that themselves can change over time. Capturing these dynamics and simulating transmissions to understand the chief sources of transmission remain important for prevention. Methods. The Progression and Transmission of HIV/AIDS (PATH 2.0) is an agent-based model of a sample of 10,000 people living with HIV (PLWH), who represent all men who have sex with men (MSM) and heterosexuals living with HIV in the U.S.A. Persons uninfected were modeled as populations, stratified by risk and gender. The model included detailed individual-level data from several large national surveillance databases. The outcomes focused on average annual transmission rates from 2008 through 2011 by disease stage, HIV care continuum, and sexual risk group. Results. The relative risk of transmission of those in the acute phase was nine-times [5th and...
Biomaterial microarchitecture: a potent regulator of individual cell behavior and multicellular organization

Insoluble cues from a cell's surrounding microenvironment have increasingly been shown to be important regulators of cell behavior. The microarchitecture of biomaterials used for 3D cell encapsulation, however, is often underappreciated as an important insoluble factor guiding cell activity. In this review, we illustrate that the subcellular physical features of a scaffold influence a range of cell behaviors, including morphology, cytoskeletal organization, migration, matrix remodeling, and long-range force transmission. We emphasize that the microarchitecture of stromal extracellular matrix (ECM)-specifically the fact that it consists of a network of long interconnecting fibers with micron and nanometer-sized diameters-is an important determinant of how cells naturally interact with their surrounding matrix and each other. Synthetic biomaterials with a microarchitecture similar to stromal ECM can support analogous cellular responses, suggesting that this fibrous microarchitecture is a key regulator of these cell behaviors. Drawing upon examples from in vitro, in silico, and in vivo studies, we compare these behaviors in fibrous matrices to those of cells cultured within nanoporous matrices (e.g., alginate and PEG gels) as well as macroporous scaffolds to highlight key differences in the cellular response to each type of microarchitecture. Understanding how microarchitecture affects cell behavior can lead to more efficient biomaterial selection when designing tissue engineered scaffolds for therapeutic applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 640-661, 2017.
Reducing Bias in Event Time Simulation via Measure Changes

Stochastic models of event timing are common to many areas, including finance, insurance, and reliability. Monte Carlo simulation is often used to perform computations for these models. The standard sampling approach, which is based on a time-scaling argument, is widely applicable but generates biased simulation estimators. This article develops a measure change technique for reducing the bias and accelerating the algorithm. If a certain bridge transform is computable for the given model, then the approach leads to unbiased estimators. Numerical results illustrate our approach.
Abstract 4044: R-ketorolac targets Cdc42 and Rac1 GTPases and alters ovarian tumor cell behaviors critical for invasion and metastasis

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Ovarian cancer (OvCa) is the 5th leading cause of cancer death in women in the US with a 5-year survival rate of 44.6%. About 70% patients are diagnosed at advanced stages with intraperitoneal dissemination, therefore identifying intracellular targets and developing effective molecules to reduce tumor metastasis have great significance for ovarian cancer therapy. Cdc42 and Rac1 are small Rho GTPase and function as molecular switches of actin reorganization which are crucial to tumor cell adhesion, migration and invasion. In previous work, our group found Cdc42 and the constitutively active Rac1b are overexpressed in primary ovarian tumor tissues and ovarian cancer cell lines. Lead identification through a high-throughput screen combined with a computational shape homology approach, identified R-ketorolac as a Cdc42 and Rac1 regulator, an activity that is distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. RhoA was unaffected by R-ketorolac. A bead-based flow cytometry assay identified R-ketorolac reduced Cdc42 and Rac1 GTPase nucleotide binding in vitro and inhibition was an allosteric mechanism of action. In cell-based assays, using Skov3ip cells, and in ascites-derived ovarian tumor cells, R-ketorolac was found to inhibit the activities of Cdc42 and Rac1 and their direct downstream effectors, the phosphorylation of p21-activated kinases (PAKs). R-ketorolac, but not S-ketorolac impeded Cdc42 mediated filopodia formation, measured based on both the length and numbers of filopodia in Skov3ip and primary OvCa cells. Cell behavior assays showed that R-ketorolac but not S-ketorolac strikingly inhibited cell adhesion, migration and invasion. In a xenograft mouse model a 50% reduction in tumor cell number and decreased total tumor burden was observed with R-ketorolac as compared to S-ketorolac treatment. Finally, in a ‘phase 0′ clinical study we found Cdc42 and Rac1 activities were reduced in a time-dependent manner after a single IV dose of racemic ketorolac treatment. In sum, we established R-ketorolac inhibition on Cdc42 and Rac1 activities and subsequent physiological consequences which are critical to tumor metastasis. Our findings provide the first demonstration of selective inhibition of Cdc42 and Rac1 GTPases by an FDA approved drug in humans. Citation Format: Yuna Guo, S. Ray Kenney, Larry A. Sklar, Tione Buranda, Tudor I. Oprea, Oleg Ursu, Sarah F. Adams, Teresa Rutledge, Carolyn Muller, Lesley Lomo, Laurie G. Hudson, Angela Wandinger-Ness. R-ketorolac targets Cdc42 and Rac1 GTPases and alters ovarian tumor cell behaviors critical for invasion and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4044. doi:10.1158/1538-7445.AM2015-4044
Rates of Spontaneous Mutation: Insights Gained Over the Last Half Century

Nikolai Timofeeff-Ressovsky understood well the need for both explicit theory and quantitation in biology. His adventures with Karl Zimmer and Max Delbruck and the somewhat romantic portrayal of those ideas by Erwin Schrodinger contributed notably to the development of population genetics and led to the modern theory of mutation. A central mystery in Timofeeff’s time was the size and composition of the gene, which he probed by the methods of radiation mutagenesis. A subsequent central mystery has been whether order may somehow underlie the apparent chaos of mutation rates . Although the first hints of order appeared in the late 1960s, the robustness of certain formulations of mutation rates did not become apparent until the 1990s. It is now clear that each of four major groups of organisms has its own characteristic rate of spontaneous mutation. The riboviruses hover at the edge of mutational meltdown, the retroelements live a few-fold less dangerously, the DNA-based microbes maintain a very small genomic rate (except in special circumstances), and the higher eukaryotes seem to have adopted a rate only a few-fold higher than the DNA-based microbes (with remarkable consequences over the course of a sexual generation). The evolutionary forces driving these characteristic rates are poorly understood.
Abstract 4554A: Simple, efficient, and quantitative approach for determination of synergism, additive effect, and antagonism of drugsin vivousing combination index method: a proposition for clinical protocol design and regulatory synergy claims

Based on the systematic dynamic rate derivations with the mass-action principle and mathematical induction-deduction, the median-effect equation of Chou, and the combination index (CI) equation and their algorithm allow quantitative determination of synergism (CI 1) (Pharmacol Rev 58:621-681, 2006). Based on Google Scholar Citations, the CI simulation has been cited 7,712 times in >800 bio-medical journals as of 10.19.2016. However, most citing papers were with experiments in vitro, relative few in vivo and rarely in clinical trials. This is despite the fact that the CI method equation, algorithm, and the CompuSyn software are the same for in vitro and in vivo, although the practical aspects such as sample size, time and cost, the readiness of the end-point measurement, and the ethical considerations are different. Our recent publication (in Fu J et al. Synergy 3: 15-30, 2016) of two-drug combination (docetaxel and T-607 compound, 1:2) against HCT-116 colon carcinoma xenograft in nude mice has demonstrated very desirable synergy. We now illustrate the experimental and data-analytical details of the experimental planning and design, execution, measurements, for docetaxel and T-Compound combination against MX-1 mammary carcinoma xenograft in nude mice. Treatment Q3Dx4 i.v. starting Day 7, and the tumor sizes and bodyweight changes measured on Days 16, 19, and 22. A total of 50 nude mice were used (each drug and combinations, 3 doses each (n=5) plus a control group of 5). Full spectrum of synergism (CI=0.79 to 0.93) were observed on Days 19 and 22. Automated simulation were carried out for dose-effect curve, ME plot, Fa-CI plot, isobologram, and Fa-DRI (Dose-Reduction Index) plot with CompuSyn software (Free download available upon registration via www.combosyn.com). This simple, efficient, “econo-green” bio-research paves the way for drug combination clinical trial design and regulatory synergy claims. Citation Format: Jianing Fu, Ting-Chao Chou. Simple, efficient, and quantitative approach for determination of synergism, additive effect, and antagonism of drugs in vivo using combination index method: a proposition for clinical protocol design and regulatory synergy claims [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 4554A. doi:10.1158/1538-7445.AM2017-4554A
The Central American Court of Justice (1907-1918): Rethinking the Word’s First Court

The Central American Court of Justice (CACJ) (1907-1918) was created with the goal of minimizing conflict between the five republics: El Salvador, Costa Rica, Guatemala, Nicaragua, and Honduras. The CACJ, however, has attracted scant scholarly attention. Nonetheless, the Court is academically significant and historically relevant. The CACJ was not only the world’s first supranational body to which states would suspend their sovereignty and submit all complaints, but also evidence that international organizations could facilitate state cooperation and create peace. Addressing the gap in the literature through extensive archival research, this study finds the following. First, the Court played an instrumental role in mediating regional peace and averting war between the republics. Second, it addressed controversial issues concerning state relations such as non-intervention, the law of the sea, and international treaty obligations. Third, due to the Court’s profound legal work, it still continues to have the potential to contribute to international law and institutions. Finally, although Washington played a significant role in the Court’s rise and demise, the Court demonstrates the ability of Latin American countries to address their own regional issues. As a result, the CACJ is a valuable underexplored subject that merits historical consideration.
First Record of Sorex tenellus from Utah

Abstract. A specimen of the Inyo shrew, Sorex tenellus, was collected in pinon-juniper woodland at 2017 m elevation in Granite Creek Canyon, Deep Creek Range, Juab Co., Utah. This is the easternmost record for this species and the first record for Utah.
Making sense of others: The use of biographical statements in Rosaura a las Diez

Marco Denevi’s Rosaura a las Diez is a novel that explores the complex relationships between law, science, and everyday life. These fields of human experience play a fundamental role in the construction of the social categories and biographical statements individuals use to understand their world. This article draws from the works of Michel Foucault and Erving Goffman to analyse the way in which Denevi explores individuals making sense of themselves and others.
Longer Duration Versus Increasing Power During Radiofrequency Ablation Yields Different Ablation Lesion Characteristics

Abstract Objectives The goal of this study was to characterize differences in ablation lesions with varying radiofrequency ablation (RFA) power and time. Background Increasing power delivery or prolonging duration can improve the efficacy of RFA. However, the extent to which ablation lesion characteristics change, based on varying degrees of power and duration, is unknown. Methods An ex vivo model consisting of viable bovine myocardium in a circulating warmed saline bath was used. An open irrigated RFA catheter was positioned with 10 g of force in the perpendicular position, and RFA was delivered at powers of 20, 30, 40, and 50 W and for various time intervals, up to a total of 90 s, at each power. An in vivo porcine thigh preparation model was used to perform RFA at 50 W for 5 s and 20 W for 30 s. Lesion volumes were analyzed. Results Greater power delivery and longer radiofrequency time increased ablation lesion size. However, compared with a proportional change in radiofrequency duration, the same proportional increase in power produced a significantly larger lesion volume (p Conclusions Varying power and duration will confer different ablation lesion characteristics that can be tailored according to the substrate/anatomy that is being ablated. This phenomenon has important implications during catheter ablation.
In frogs, even leptin function doesn't escape metamorphosis

![Graphic][1] If you think your pubescent years were incommodious, you should talk to a frog. We humans see some changes here and there, sure. But for a tadpole metamorphosing into a frog, so many profound changes occur that, were it not known to science, this developmental process would
Standardisierungswettbewerb zwischen parametrisierbarer Standardsoftware und komponentenbasierten Anwendungssystemen

Aus einer technologischen Perspektive sind Business Frameworks ein vielversprechender Ansatz Unternehmungen auf effiziente Art und Weise mit betriebswirtschaftlichen Anwendungssystemen zu versorgen. Trotz dieser Vision kann man am Markt bisher nicht feststellen das Frameworkanbieter die Marktstellung etablierter Standardsoftwarehersteller bedrohen. In dieser Arbeit wird modellbasiert der Wettbewerb zwischen Herstellern von Standardsoftware und Frameworkanbietern untersucht. Der Fokus liegt dabei auf den zwei wesentlichen Einflusfaktoren: dem Netzeffekt und der Wirkung von Kompatibilitats-bzw. Standardisierungsentscheidungen. Auf Basis des Modells konnen Empfehlungen uber die strategische Positionierung von Softwarehausern im Standardisierungswettbewerb abgeleitet werden.
Vesicocolonic Fistulas in Diverticulitis

AbstractDiverticulitis is a disease affecting patients in the fifth to sixth decades. The charts of 12 patients with vesicocolonic fistulas secondary to diverticulitis were reviewed. Their presentation was primarily urological with pneumaturia present in 10 of 12 patients and fecaluria present in 5 of 12. The process of fistulization occurs in stages. If the incipient stage can be identified early fistulization can be prevented and the morbidity and mortality rates will be reduced significantly. In older patients with bladder irritation (with or without positive urine cultures) a high degree of suspicion for diverticular disease will ensure an accurate diagnosis earlier. Patients with pneumaturia or fecaluria present less of a diagnostic challenge. Cystoscopy is a reliable procedure and we recommend its use in discovering a vesicocolonic fistula. Surgical therapy should be individualized for each patient and good results were obtained with primary resection as well as staged repair.
The activation of chymotrypsinogen; isolation and identification of a peptide liberated during activation.

Reactions attending the conversion of precursors of proteolytic enzymes to the active form are distinguished by several features of unusual interest: (a) they are enzyme-catalyzed; (b) they are irreversible; (c) they involve the opening of a limited number of peptide bonds; (d) they provide an experimental system for the study of the final steps in formation of a biologically specific protein and of the relation of chemical structure to biological activity of proteins. In recent studies in this laboratory, including the present work, several intermediates formed during the activation of chymotrypsinogen have been recognized by a combination of methods. These have included electrophoresis, end-group analysis, enzymatic activity, peptide analysis, and sedimentation. As a result of the present experimental study, which dealt in particular with the nature of the peptide released during the rapid activation of chymotrypsinogen, it has been possible to identify the nature of the limited number of peptide bonds hydrolyzed during the activation process.
Genetics of Cellular Aging

Body homeostasis is maintained by positive and negative regulatory signals in the various cells and organs of an animal. Changes in regulation of these signals could lead to loss of cell proliferative response, as observed in the aging immune system, or alternatively to uncontrolled cell division, one step in the progression toward neoplasia. There is good evidence that the likelihood of both these changes increases with age. Therefore, changes in the regulation of cell proliferation are an extremely important component of not only the general aging phenotype, but also the onset of tumorigenicity. The loss of cell proliferative ability of normal animal cells in culture following the accruement of a defined number of population doublings is well documented. This phenomenon has been proposed as a model foraging at the cellular level [1]. Data in support of the model include the observations that a direct correlation exists between species life span and in vitro life span [2], but that this correlation is inverse with donorage [3–7]. The frequency of reversal of the senescence phenotype (i.e., immortalization) varies greatly with different animal species. The probability of immortalization (spontaneous and induced) in mouse cells is extremely high, whereas in human cells spontaneous immortalization has never been shown to occurand induced immortalization using agents such as virus or chemical carcinogens is very low (probably < 10−8). Because of this greater genomic stability the majority of studies in the field of cellularaging have utilized human cells.
The clinical evaluation of chronic cough.

Cough itself is not an illness but the symptom of an underlying stimulus or disease; therefore, evaluation and treatment of cough should be directed at the underlying illness rather than at the cough itself.
Reading Rescue: A Follow-Up on Effectiveness of an Intervention for Struggling Readers.

The authors examined whether Reading Rescue continues to be an effective literacy intervention and factors that impact its effectiveness. Data were collected on 143 first-grade students, tutored by...
Midlatitude Mesoscale Ocean-Atmosphere Interaction and Its Relevance to S2S Prediction

Abstract Mesoscale eddies in the ocean are the dynamical analog of atmospheric weather. Satellite observations have identified significant correlations between mesoscale sea surface temperature (SST) anomalies and near-surface atmospheric flow. A hierarchy of mechanistic simulations is carried out using high-resolution regional climate models to assess the impact of mesoscale SST anomalies in the North Pacific on atmospheric circulation above the boundary layer. By comparing ensembles of simulations using high-resolution SST boundary conditions at the surface to those using smoothed SST, it is demonstrated that oceanic mesoscale eddies in the Kuroshio Extension Region (KER) have both local and remote influences on the atmospheric storm track. The local influence is associated with increased vertical moisture flux in the presence of oceanic eddies, leading to enhanced diabatic heating and intensified baroclinic cyclogenesis. The remote influence manifests itself as a shift in the Pacific storm track that affects winter rainfall patterns over the West Coast of the United States. As oceanic mesoscale eddies persist and evolve on sub-seasonal to seasonal (S2S) timescales, it is argued that their interaction with atmosphere can contribute to S2S predictive skill. This highlights the need for increased horizontal resolution to represent this mode of air-sea interaction adequately in S2S forecast models.
Role Annotated Speech Recognition for Conversational Interactions

Speaker Role Recognition (SRR) assigns a specific speaker role to each speaker-homogeneous speech segment in a conversation. Typically, those segments have to be identified first through a diarization step. Additionally, since SRR is usually based on the different linguistic patterns observed between the roles to be recognized, an Automatic Speech Recognition (ASR) system is also indispensable for the task in hand to convert speech to text. In this work we introduce a Role Annotated Speech Recognition (RASR) system which, given a speech signal, outputs a sequence of words annotated with the corresponding speaker roles. Thus, the need of different component modules which are connected in a way that may lead to error propagation is eliminated. We present, analyze, and test our system for the case of two speaker roles to show-case an end-to-end approach for automatic rich transcription with application to clinical dyadic interactions.