cssi/SciSciGPT-SciSciNet huggingface dataset:
Intertemporal Discount Factors as a Measure of Trustworthiness in Electronic Commerce

In multiagent interactions, such as e-commerce and file sharing, being able to accurately assess the trustworthiness of others is important for agents to protect themselves from losing utility. Focusing on rational agents in e-commerce, we prove that an agent's discount factor (time preference of utility) is a direct measure of the agent's trustworthiness for a set of reasonably general assumptions and definitions. We propose a general list of desiderata for trust systems and discuss how discount factors as trustworthiness meet these desiderata. We discuss how discount factors are a robust measure when entering commitments that exhibit moral hazards. Using an online market as a motivating example, we derive some analytical methods both for measuring discount factors and for aggregating the measurements.
Long-Distance On-chip Communication Using GasP

We present several novel asynchronous FIFOs that can be used for long-distance on-chip communication. All FIFOs are based on GasP circuits with GasP repeaters. We have designed the GasP circuits and GasP repeaters such that their forward latencies match the forward latencies of the latches and repeaters in the data path. Simulation results show that, when data must be moved over long distances with minimal latency, these novel GasP FIFOs with GasP repeaters perform substantially better than traditional GasP FIFOs without repeaters.
Semiempirical Model of the Vapor-Liquid Phase Behavior of the Hydrogen Chloride-Water System

A simple, accurate, and widely applicable semiempirical vapor−liquid equilibrium model is developed for the HCl−water system. The model is based on the modified Raoult's law, adjusted to include a function known as the “pseudo-vapor pressure.” The resulting set of equations relate total pressure, liquid bulk (nonionized) composition, vapor composition, and temperature. The parameters were fit to a wide range of data available in the literature (−10 to 200 °C, 0.00268−66.1 atm, and 2−54.9 wt % HCl) that includes the supercritical region. The final equations are demonstrated to allow straightforward calculation of azeotropes and dew points.
Learning from yesterday's mistakes to fix tomorrow's problems: When functional counterfactual thinking and psychological distance collide

Functional counterfactual thinking involves a unique set of circumstances where one can both reflect on past events and imagine future possibilities. A key aspect of a counterfactual's functionality is that insight about past mistakes is converted into plans for future action, thereby improving self-regulatory success. If counterfactual thinking is a self-regulatory tool, then it should be similarly impacted by psychological mechanisms that influence peoples' ability to improve future outcomes. The current research tested one such mechanism, psychological distance. Using a sequential priming paradigm, Experiment 1 showed that functional counterfactual thinking is sensitive to changes in temporal distance. Negative events in the recent versus distant past facilitated relevant behavioral intention judgments. Additionally, functional counterfactual thinking was sensitive to changes in the relevant behavioral intention's temporal distance, such that counterfactual judgments facilitated behavioral intentions set to occur in the near but not distant future (Experiment 2). Together, this research creates new connections between functional counterfactual thinking and psychological distance. Copyright (C) 2012 John Wiley & Sons, Ltd.
The removal of aqueous silica from dilute aqueous solution

Abstract The adsorption characteristics of orthosilicate on hydrous γ-Al2O3 from dilute aqueous solution (10−4 to 10−3 M) at constant ionic strength (0.1M NaCl) was investigated in the laboratory. The extent of adsorption is affected by pH, concentration of silicate, or the relative concentration of silicate and oxide surface. With short reaction time (24 hours), adsorption is the major interfacial reaction and follows an S-type adsorption isotherm. The steepness of the S-curve isotherm is influenced by the degree of equilibrium. The slower the adsorption reaction is, the flatter the S-curve becomes. Two steps, an initial fast followed by a second slow, of silicate removal were observed. The first fast step, which lasts for about one to two hours, depends greatly on pH and has the following expressions: −d[Si]/dt = 1.3 × 10−3 [A]2[H+]−0.5[Si]1.5; pH 9. The second slow step is a first-order form with respect to the concentration of silicate. The specific rate constant depends on pH, concentration of silicate and surface area. Specific chemical energy contributes significantly to the adsorption of silicate and a value of ⋍−12RT was found.
Blow-up estimates for a nonlinear hyperbolic heat equation

Consider the Cauchy problem for \[ \varepsilon u_{tt} + u_t - u_{xx} = F(u); \]u represents the temperature when the standard Fourier law $q = u_x $ (q flux) is relaxed and $F(u)$ is a nonlinear source of energy. It is established that the solution exists for $0 < t < \phi _\varepsilon (x)$, and it blows up as $t \to \phi _\varepsilon (x)$. Further, $\phi _\varepsilon (x) \to T_0 $ as $\varepsilon \to 0$ where $T_o $ is the blow-up time for $u_t - u_{xx} = F(u)$
Competition and Allometry in Kochia scoparia

Abstract Comparisons between crowded and uncrowded Kochia scoparia individuals demonstrate pronounced effects of competition on plant allometry as well as on the distributions of different aspects of size. Non-destructive measurements of height and stem diameter and, for a subset of the populations, the number and length of leaves and branches, were taken at three times, and the plants were harvested after the third measurement. The sequential measurements afforded the opportunity to obtain information of the effects of competition on allometric growth trajectories of individuals, as well as on static inter-individual allometric relationships. The distributions of most size measures appeared to be normal for the uncrowded population. Crowded populations developed a negatively-skewed height distribution and a high-inequality mass distribution, whereas the diameter distributions remained normal. Plants grown without neighbours showed simple allometric relationships between height, diameter and weight. For isolated plants, the 'static' allometric relationship between plants of different sizes and the allometric growth trajectory of individuals were similar. Crowded populations showed complex allometry; the static inter-individual relationships between height, diameter and weight were curvilinear (on log-log scale). There were large differences in the allometric growth slopes of uncrowded vs. crowded plants. Allometric relationships between stem diameter and plant mass, and between total length of leaves and total length of branches, did not seem to be altered by competition. The data suggest that height was the most important aspect of size influencing future growth of individuals in the crowded population. Only plants above a certain height were able to continue to grow from the second to third measurement in the crowded population. This supports the hypothesis that asymmetric competition for light is the cause of the allometric changes and of the increase in size variability due to competition.
Computed tomography postacquisition data correction for system alignment errors

A critical issue in obtaining high-quality images from a computed tomography system is the mechanical alignment of the data acquisition system. This paper will compare two methods of measuring and correcting errors introduced into second-generation computed tomography data sets from misalignment of the system. Both of these methods use a projection data set from a complete scan of an object as a starting point. One method is an iterative method that looks at residual errors in selected portions of the reconstructed image. The other method requires that the centroids of the projection data coincide with the centroid of the object. It will be shown that the centroid registration algorithm can be used to accurately measure a number of important computed tomography system alignment parameters and is mathematically efficient. The residual error algorithm will be shown to give less satisfactory results.
Maximum cut on line and total graphs

The maximum cut problem is proved to be polynomial time solvable on line graphs, while it is proved to be NP-hard on the related class of total graphs.
“Dry Hole” in Venezuelan Mesoscale Cyclone

Abstract An unusual series of radar photographs was encountered in a major rainstorm in Venezuela in 1972. An elongated hole in the S-band radar presentation worked its way from the echo edge toward the center, then became an island and finally disappeared after one hour. The suggested mechanism for this event is a vertical wave motion superimposed on a rotating mesoscale cyclone.
The China that was not to be: nostalgia and the exilic imagination of Taiwan's mainland diaspora

Studies of diaspora typically inquire after culturally homogenous populations driven from their homelands and living as subalterns in their new environs. In this paper, we look at such an exiled population living not at the periphery, but in the upper rungs of its host society, and as such is able to impose its ancestral language, literature of nostalgia, and exilic world view upon its host population. We show how mainland refugees of the Chinese Civil War entering Taiwan between 1945 and 1949 have managed, for some 40 years, to import an exoglossic linguistic standard, set literary trends born of nostalgic longing, define a culture of pan-Chinese nationalism, and impose an imaginary geography of historical China upon the local population. We further illustrate how this nostalgia-tinged interpretation of Chinese history and culture has shaped a generation of Western views of China and imparted a literary and cultural legacy far beyond expectations generated by the diaspora's small numbers. Finally, as tra...
A research center for augmenting human intellect

This paper describes a multisponsor research center at Stanford Research Institute in man-computer interaction.
Editor's Introduction to Karl Llewellyn's 'The Theory of Rules'

From 1938 to 1940 Karl Llewellyn worked on and substantially completed a book-length manuscript entitled The Theory of Rules. With the book almost completed, Llewellyn turned to other things, primarily his work on law and anthropology and his efforts relating to the Uniform Commercial Code. The book on rules remained uncompleted at his death, and is now to be published by the University of Chicago Press in 2010, edited and with an Introduction by Frederick Schauer, David and Mary Harrison Distinguished Professor of Law at the University of Virginia. The Introduction situates The Theory of Rules within the corpus of Llewellyn’s work, within the Legal Realist perspective on legal rules, and within the jurisprudential and philosophical literature on rules in general.
The South Carolina Archives: A Decade of Change and Program Development

This article traces the development of the archival program at the South Carolina Department of Archives and History (SCDAH) since the mid-1980s. Like most other state archives, the SCDAH has had to deal with some major organizational and resource changes in the past decade. Among the topics and issues addressed are: the impact of increasing state fiscal constraints, strategic planning and Total Quality Management, information technology and electronic records, federal grants, and the opportunities for statewide archival involvement through the State Historical Records Advisory Board. The article concludes with consideration of the prospects for further and potentially far-reaching changes in the program relating to the construction of the South Carolina History Center which is scheduled to open in the spring of 1998.
PROVE-IT to IMPROVE-IT: Why LDL-C Goals Still Matter in Post-ACS Patients

The sword of Damocles, a term derived from Greek mythology, refers to the perpetual sense of fear and dread of death under which specific individuals, usually leaders, must live. According to the Greek myth, Damocles, a courtier, switched places with King Dionysius II, the ruler of Syracuse (modern
Nasal carriage of Staphylococcus aureus in physician assistant students: initial prevalence and transmission during clinical rotations.

Purpose: This study evaluated physician assistant (PA) students for nasal carriage of Staphylococcus aureus (prerotations) and then again just prior to graduation. It also attempted to correlate initial and subsequent sample results with subject-specific survey data relating to students’ general medical, social, behavioral, and geographical situations. Methods: Nasal swab cultures were self-collected using standardized techniques. Colonies suspicious for Staph underwent further workup to determine if Staphylococcus aureus was present. Results: Nine (eight females, one male) of 34 subjects (26.5%) were positive for Methicillin-sensitive Staphylococcus aureus (MSSA) in the nares at baseline and all nine subjects remained positive during the second sampling. No subjects were found to have Methicillin-resistant Staphylococcus aureus (MRSA) at baseline and no subjects were positive for MRSA during phase two sampling. Routine sharing of drinks from common glassware was identified in all positive subjects, while subjects negative for colonization reported only seldom or no participation in that activity (P < 0.001). Conclusions: Clinical rotations did not appear to alter carriage status. However, a strong association between nasal carriage and participation in certain social behaviors was observed. Feature Editor’s Note: The health and well-being of students enrolled in physician assistant (PA) programs are top priorities of PA educators. PA students have the potential for significant exposure to infectious organisms including methicillin-resistant Staphylococcus aureus (MRSA). This study attempts to document the outcomes of a small cohort from a single PA program, pre- and postclinical rotation periods, specifically to determine the rate of transmission/conversion to Staphylococcus aureus colonization during clinical rotations. In addition, the author explores identifiable behaviors and social factors that may contribute to conversion rates. The findings of an association between female gender, Staphylococcus aureus colonization, and shared glassware observed in this small study are intriguing and may warrant further investigation.
Socialist Law and the Civil Law Tradition

Revolutions leading to socialist legal systems occurred in countries of the civil law tradition, not in common law countries.' Eastern Europe had been controlled by Germany, Austria-Hungary, and Russia, all of which were civil law countries.2 China had in the early twentieth century incorporated elements of civil law as an overlay on its Confucian base. Vietnam used French law from the late nineteenth century.3 Cuba had a legal system established by Spain. After socialist revolutions, significant changes were made in the legal systems of these countries. Just how significant these changes have been is a matter of controversy. Many Western and socialistcountry comparatists argue that sufficient innovations have been introduced to constitute socialist law a separate family of law. Other comparatists reject this separationist thesis but have not systematically scrutinized the separationists' arguments.4 This article examines those arguments, taking particular account of developments of the late 1980s in socialist law. The issue of the proper classification of socialist law, it will be suggested, is of more than academic interest. Improper classification yields misunderstanding about the role and function of law in both socialist and non-socialist legal systems.
Association of Thrips with Powdery Mildews

Thrips tabaci has been observed associated with powdery mildew infections on grape, rose, strawberry, cantalope, clover, and Oenothera. In dish cultures thrips transferred to mildewed leaves of gra...
Integration in the Inland Empire Region of the Pacific Northwest

the group members might give the impression of an extreme stability. Yet this impression is spurious. In such societies there are great amounts of hostile impulses repressed in each group member which only wait for the appropriate moment for violent expression. So long as there is an external enemy on whomn these hostilities can be vented there is no danger of internal disruption. Nevertheless such a society is founded on a volcanic ground. The need for a scapegoat in such social situations is always great and is the best proof of the great internal tension. If there is a lack of an external enemy the presence of a weak minority group that can be treated as an external enemy is a dynamic necessity for the existence of such an autocratic social organization. After the minority group is fully exterminated, the revolutionary danger becomes imminent. The paradoxical situation arises that in such societies the scapegoat must be treated at least to some degree with gloves: its existence must be saved in order to serve as a permanent outlet for the accumulated and repressed hostilities of the group memnbers against each other and against their tyrannical ruler.
Generations and the Expression of Symbolic Racism

beliefs. The study is based on in-depth interviews with the adult children of the men first interviewed by Robert E. Lane for Political Ideology (1962). While little evidence pointed to the direct imprinting of specific racial beliefs on the cognitive level, there did seem to be a transfer of underlying attitudes on the affective level. The children with fathers who opposed miscegenation tended to be the people who opposed quotas, affirmative action, and bussing. It is argued that the familial atmosphere produced a reservoir of racism beneath the surface of otherwise tolerant beliefs. The fathers' opposition to miscegenation may have established a negative affective evalution of blacks within the second generation which remained even after schools, peers, the media and other socializing agents fundamentally transformed the cognitive constructions through which opinions about race relations were expressed. Issues laden with racial symbolism would then activate the negative affect, producing opposition to policies designed to achieve equality between races.
Nothing but a hound dog

Deep learning algorithms have beaten world champions in the game of Go and have even tackled challenges as critical as finding cats in online videos. In recent work, Kelley et al . applied these methods to genome sequences, because predicting a region’s function simply from a sequence of bases has
Molecular structure of [CpFe(CO) 2 ] 3 In

The molecular structure of [CpFe(CO)2]3In (Cp=η5-C5H5) has been determined and contains a planar, three-coordinate indium center bound to three CpFe(CO)2 moieties by unsupported In–Fe bonds. The orientation of the CpFe(CO)2 units relative to the Fe3In plane precludes π-type interaction between iron and indium, while comparison with the isostructural gallium analog suggests the orientation of the CpFe(CO)2 units is controlled by the size of the central atom and the inter-ligand steric repulsion. Crystal data: monoclinic, monoclinic, C2/c, a = 26.911(5), b = 10.838(2), c = 16.474(3)A, β = 111.63(3)°, V = 4465(2)A3 and, Z = 8.
Cultures and Languages across the Curriculum in Global Health

Institutions of higher education have placed increasing importance on internationalising their curricula over the past 10 years. At Duke University, a private university in the southern United States, these efforts have led to a unique partnership between the Romance Studies Department and the Duke Global Health Institute (DGHI) that focuses on a curriculum design based on the Cultures and Languages Across the Curriculum (CLAC) model.
Abstract 3658: A novel microtubule associated RNA binding protein matrin 3 act as a tumor suppressor by regulating mitotic spindle organizing proteins in triple negative breast cancers

Microtubule-targeting drugs are widely used as cancer chemotherapeutic agents and they have been shown to inhibit mitotic progression and interphase signaling. Despite their use as a first line treatment for cancer, many patients develop resistance to microtubule-targeting drugs leading to early relapse and shorter survival. Moreover, the quality of life for patients who do survive is often substantially reduced due to the toxicity associated with these drugs. Therefore, identification of new factors that determine the effectiveness of microtubule-targeting agents will not only facilitate a better understanding of the mechanisms of acquired drug resistance but will also be amenable to therapeutic interventions. We discovered a novel microtubule associated protein “Matrin 3 (MATR3)” that is known to bind to RNA and play a critical role in RNA transport and RNA stabilization. Our results revealed that MATR3 acts as a potent tumor suppressor as it inhibits long-term growth, migration, invasion as well as tumor growth of triple negative breast cancer (TNBC) cells in vivo. We demonstrated that MATR3 overexpression induced cell cycle arrest and apoptosis in TNBC cells. Furthermore, analysis of breast cancer samples showed a significantly lower expression of MATR3 when compared to normal adjacent tissues. Importantly, our RNA immunoprecipitation (RIP)-seq analysis showed that MATR3 controls expression of several mitotic spindle organizing proteins by binding to their RNA. Interestingly, we found that these MATR3 regulated proteins were highly altered in breast cancer patients. In conclusion, we identified a novel RNA-binding protein that inhibits breast cancer growth and progression suppressor by regulating microtubule dynamics. Citation Format: Panneerdoss Subbarayalu, Subapriya Rajamanickam, Suryavathi Viswanadhapalli, Benjamin C. Onyeagucha, Vijay K. Eedunuri, Nicholas Dybdal-Hargreaves, Santosh Timilsina, Hima Bansal, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, John C. Herr, Susan L. Mooberry, Manjeet K. Rao. A novel microtubule associated RNA binding protein matrin 3 act as a tumor suppressor by regulating mitotic spindle organizing proteins in triple negative breast cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3658.
Multi-scale classification based lesion segmentation for dermoscopic images

This paper presents a robust segmentation method based on multi-scale classification to identify the lesion boundary in dermoscopic images. Our proposed method leverages a collection of classifiers which are trained at various resolutions to categorize each pixel as “lesion” or “surrounding skin”. In detection phase, trained classifiers are applied on new images. The classifier outputs are fused at pixel level to build probability maps which represent lesion saliency maps. In the next step, Otsu thresholding is applied to convert the saliency maps to binary masks, which determine the border of the lesions. We compared our proposed method with existing lesion segmentation methods proposed in the literature using two dermoscopy data sets (International Skin Imaging Collaboration and Pedro Hispano Hospital) which demonstrates the superiority of our method with Dice Coefficient of 0.91 and accuracy of 94%.
Accuracy of magnetic resonance imaging in diagnosing lateral ankle ligament injuries: A comparative study with surgical findings and timings of scans.

Objective This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in diagnosing lateral ankle ligament injuries and the effect of differences in time duration from injury to MRI.
Quasianalyticity and Semigroups

This chapter contains a development for linear semigroups which is of interest in the theory of probability and other areas.
Binge Drinking, Greek-Life Membership, and First-Year Undergraduates: The “Perfect Storm” for Drugging Victimization

ABSTRACTDrugging victimization is an understudied phenomenon. This study examines the relationship between the campus party culture and drugging victimization. Campus party culture has been shown to influence risk of other types of victimization, and there is reason to believe it may also influence drugging victimization. Using three behavioral indicators of participation in the campus party culture—binge drinking, Greek life membership, and first-year student status—this study estimates the main effect of each indicator, and their interaction, on undergraduates’ rates of drugging victimization. Estimating a generalized linear model using a large random sample (N = 6,931) from three universities, results show that each party culture variable and their three-way interaction significantly influenced students’ rate of drugging victimization. Sorority members who were first-year students and binge drank at least once in the past month had significantly higher rates of drugging victimization compared to all ot...
Halobacterium sp. NRC-1: A Review

Halobacterium sp. NRC-1 is the halophilic bacterium. This halophile has a great potential to survive on high salinity conditions. The genome of this bacterium has sequenced. The studies have done at metagenomics level, which include the Identification and Molecular Characterization. Identification of this extreme halophile was done by 16S ribotyping and PCR amplification using universal primers FD1 and rP1. The sequences than compared with already sequenced genomes of halophiles. The post genomic tools and microarrays were applied for sequencing. Halobacterium sp. NRC-1 transcriptional profiling showed that it is highly responsive to the environment and give specific responses at gene expression level. There is a need for extensive research at metaproteomic level. To study the expression and function of proteins, whole protein profiling of this specie need to be studied.
An Identity-Based Motivation Framework for Self-Regulation

Will you be going to that networking lunch? Will you be tempted by a donut at 4 p.m.? Will you be doing homework at 9 p.m.? If, like many people, your responses are based on your gut sense of who y...
Toward Cost-Effective Manufacturing of Silicon Solar Cells: Electrodeposition of High-Quality Si Films in a CaCl2 -based Molten Salt.

Electrodeposition of Si films from a Si-containing electrolyte is a cost-effective approach for the manufacturing of solar cells. Proposals relying on fluoride-based molten salts have suffered from low product quality due to difficulties in impurity control. Here we demonstrate the successful electrodeposition of high-quality Si films from a CaCl2-based molten salt. Soluble SiIV−O anions generated from solid SiO2 are electrodeposited onto a graphite substrate to form a dense film of crystalline Si. Impurities in the deposited Si film are controlled at low concentrations (both B and P are less than 1 ppm). In the photoelectrochemical measurements, the film shows p-type semiconductor character and large photocurrent. A p–n junction fabricated from the deposited Si film exhibits clear photovoltaic effects. This study represents the first step to the ultimate goal of developing a cost-effective manufacturing process for Si solar cells based on electrodeposition.
A 10-Year Survey of Tropical Cyclone Inner-Core Lightning Bursts and Their Relationship to Intensity Change

AbstractThis study seeks to reconcile discrepancies between previous studies analyzing the relationship between lightning and tropical cyclone (TC) intensity change. Inner-core lightning bursts (ICLBs) were identified from 2005 to 2014 in North Atlantic (NA) and eastern North Pacific (ENP) TCs embedded in favorable environments (e.g., vertical wind shear ≤ 10 m s−1; sea surface temperatures ≥ 26.5°C) using data from the World Wide Lightning Location Network (WWLLN) transformed onto a regular grid with 8-km grid spacing to replicate the expected nadir resolution of the Geostationary Lightning Mapper (GLM). Three hypothesized factors that could impact the 24-h intensity change after a burst were tested: 1) prior intensity change, 2) azimuthal burst location, and 3) radial burst location. Most ICLBs occurred in weak TCs (tropical depressions and tropical storms), and most TCs intensified (remained steady) 24 h after burst onset in the NA (ENP). TCs were more likely to intensify 24 h after an ICLB if they wer...
Carotid Endarterectomy Performed before the Weekend is Associated with Increased Length of Stay.

Objective Length of stay (LOS) is commonly used to gauge hospital resource utilization and can affect hospital profit margin. Other fields of surgery have showed that operations performed close to the weekend have longer LOS and higher patient morbidity. Our goal was to investigate whether asymptomatic patients undergoing elective carotid endarterectomy (CEA) earlier in the week had a shorter LOS and improved clinical outcomes compared to those treated before the weekend. Methods The Vascular Quality Initiative database was queried for elective weekday CEAs performed for asymptomatic carotid stenosis from 2005 to 2017. Univariate and multivariate analyses were completed to compare outcomes based on the day of the week. Results There were 26,882 asymptomatic CEAs performed on Monday (20.3%), Tuesday (23.0%), Wednesday (21.3%), Thursday (18.8%), and Friday (16.6%). The mean patient age was 70.5 years, and 59.2% were male. Thirty-day mortality (0.4%) and perioperative complications including stroke (1.4%), myocardial infarction (0.7%), and return to the operating room (1.5%) were not significantly different across weekdays. Patients were discharged on statins in 84.2% of cases and aspirin in 91.5% of cases. The mean LOS ranged from 1.6 ± 2.2 days to 1.8 ± 3.2 days. CEAs performed on Fridays had a longer LOS (1.8 ± 2.4; P Conclusion Asymptomatic CEA performed before the weekend was associated with longer LOS although there were no differences in perioperative mortality, morbidity, and discharge medication compliance. Such LOS increase, albeit small, may affect the hospital profit margin for the procedure and performing an elective CEA on asymptomatic patients earlier in the week may benefit in a shorter LOS. Improved team staffing and resources on weekends are potential areas for improvement for earlier discharge; however, further investigation is needed.
Biology of CNS lymphoma and the potential of novel agents

Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease. A body of genetic evidence strongly suggested that primary CNS lymphomas (PCNSLs) are likely largely dependent on NF-κB prosurvival signals, with enrichment of mutations involving the B-cell receptor pathway, in particular myeloid differentiation primary response 88 and cluster of differentiation 79B. The first set of early-phase investigations that target NF-κB in PCNSL have now been completed and support the NF-κB hypothesis but at the same time reveal that much work needs to be done to translate these results into meaningful advances in survival for a large fraction of patients. Insights into secondary prosurvival pathways that mediate drug resistance is a priority for investigation. Similarly, further evaluation of the immune-suppressive mechanisms in the CNS lymphoma tumor microenvironment is requisite for progress. Combinatorial interventions that promote the antitumor immune response have significant potential. With increasing availability of targeted agents, there is also a need to develop more sensitive imaging tools, not only to detect this highly invasive brain neoplasm but also potentially to define an evolving molecular phenotype to facilitate precision medicine.
Validation of Isometric Tetanic Force as a Measure of Muscle Recovery After Nerve Injury in the Rabbit Biceps

Purpose The purpose of this study was to describe and validate a technique for measurement of isometric tetanic force (ITF) in the rabbit biceps muscle. Materials and methods Eighteen New Zealand White rabbits were randomized to test either the right side or the left side first. Under propofol anesthesia, the brachial plexus and biceps brachii were exposed. The middle trunk (C6, C7) was secured in a bipolar electrode. Compound muscle action potential (CMAP) was measured. The proximal, tendinous portion of the biceps was severed at the shoulder and clamped in a custom-made force transducer. Muscle preload and electrical stimulation variables were optimized to obtain the highest tetanic muscle contraction. Wet muscle weight (WMW) and nerve histomorphometry were analyzed. Statistical analysis was performed to determine side-to-side equivalence. Results The rabbit biceps muscle force demonstrated side-to-side equivalence with overlapping 95% confidence intervals (95% CI). The right side, expressed as a percentage of the left, averaged 99.69% (95% CI, 88.89%–110.5%). The WMW of the right expressed as a percentage of the left was 98.9% (95% CI, 95.8%–102%). Conclusions The ITF is equivalent from side to side in the rabbit as demonstrated by the high degree of overlap in the 95% CIs for each side. The width of the 95% CI implies that there is more variability in the rabbit upper extremity than for the lower extremity of the rabbit or rat models, and researchers should take this into account when performing sample size estimates in pre-experimental planning. Clinical relevance The rabbit biceps muscle ITF measurements can be used to measure motor recovery in a rabbit model of brachial plexus injury and compared with the contralateral uninjured side.
Insurgent Democracy: The Nonpartisan League in North American Politics

Review of: "Insurgent Democracy: The Nonpartisan League in North American Politics," by Michael J. Lansing.
Reduced thermal tolerance during salinity acclimation in brook trout (Salvelinus fontinalis) can be rescued by prior treatment with cortisol

ABSTRACT The aims of this study were to assess whether thermal tolerance of brook trout ( Salvelinus fontinalis ) is affected during seawater (SW) acclimation and to investigate the role of cortisol in osmoregulation and thermal tolerance during SW acclimation. Freshwater (FW)-acclimated brook trout at 18°C ( T acc ) were exposed to SW for 16 days, whilst maintaining a FW control. Fish were examined for critical thermal maximum (CT max ) 0 (before), 2, 5 and 16 days after SW exposure, and sampled at T acc and CT max for analysis of plasma cortisol, glucose and Cl − , gill Na + /K + -ATPase (NKA) activity and heat shock protein 70 (HSP70) abundance, and white muscle water content. At 2 days in SW, CT max was significantly reduced (from 31 to 26°C), and then recovered by 16 days. This transient decrease in thermal tolerance coincided with a transient increase in plasma Cl − and decrease in muscle moisture content. Salinity itself had no effect on gill HSP70 abundance compared with the large and immediate effects of high temperature exposure during CT max testing. To examine the role of cortisol in osmoregulation, brook trout were administered a cortisol implant (5 and 25 μg g −1 CORT) prior to SW exposure. Both CORT doses significantly increased their capacity to maintain plasma Cl − during SW acclimation. Treatment with the 25 μg g −1 CORT dose was shown to significantly improve CT max after 2 days in SW, and CT max was associated with plasma Cl − and muscle moisture content. These findings indicate that brook trout are sensitive to temperature during SW acclimation and that thermal tolerance is associated with ion and water balance during SW acclimation.
Anterior laxity, lateral tibial slope, and in situ ACL force differentiate knees exhibiting distinct patterns of motion during a pivoting event: A human cadaveric study.

Abstract Knee instability following anterior cruciate ligament (ACL) rupture compromises function and increases risk of injury to the cartilage and menisci. To understand the biomechanical function of the ACL, previous studies have primarily reported the net change in tibial position in response to multiplanar torques, which generate knee instability. In contrast, we retrospectively analyzed a cohort of 13 consecutively tested cadaveric knees and found distinct motion patterns, defined as the motion of the tibia as it translates and rotates from its unloaded, initial position to its loaded, final position. Specifically, ACL-sectioned knees either subluxated anteriorly under valgus torque (VL-subluxating) (5 knees) or under a combination of valgus and internal rotational torques (VL/IR-subluxating) (8 knees), which were applied at 15 and 30° flexion using a robotic manipulator. The purpose of this study was to identify differences between these knees that could be driving the two distinct motion patterns. Therefore, we asked whether parameters of bony geometry and tibiofemoral laxity (known risk factors of non-contact ACL injury) as well as in situ ACL force, when it was intact, differentiate knees in these two groups. VL-subluxating knees exhibited greater sagittal slope of the lateral tibia by 3.6 ± 2.4° (p = 0.003); less change in anterior laxity after ACL-sectioning during a simulated Lachman test by 3.2 ± 3.2 mm (p = 0.006); and, at the peak applied valgus torque (no internal rotation torque), higher posteriorly directed, in situ ACL force by 13.4 ± 11.3 N and 12.0 ± 11.6 N at 15° and 30° of flexion, respectively (both p ≤ 0.03). These results may suggest that subgroups of knees depend more on their ACL to control lateral tibial subluxation in response to uniplanar valgus and multiplanar valgus and internal rotation torques as mediated by anterior laxity and bony morphology.
From Graduate to Professor: Changing Perspectives on Field Schools

What is the role of the field school in the education of graduate students and in the early professional life of professors? Derived from the experience of new tenure-track professors, this chapter attempts to answer this question. Key themes discussed include how graduate students learn to run a field school and the gaps in their education, the importance of the field school for junior faculty, and the place of the field school in larger disciplinary practices. What emerges is a picture of the field school as a repeated “rite of passage,” one that would benefit the discipline more with thoughtful engagement at both an instrumental and an epistemological level.
Inhibitors of Topoisomerase I Function

As noted elsewhere in this book, the locus of action of camptothecin (CPT) (1) (Fig. 1) as an antitumor agent involves the noncovalent binding of this agent to the covalent binary complex formed between topoisomerase I (TOP-I) and DNA (Fig. 2) (1). Although the equilibrium between free enzyme and the enzyme-DNA binary complex normally lies far toward free enzyme and DNA, in the presence of CPT, the equilibrium is rapidly displaced toward ternary complex (2). At this level, the action of CPT on TOP-I function is entirely analogous to those of several agents that inhibit the function of topoisomerase II, including 4-(9-acridinylamino)-N-(methanesulfonyl)-m-anisidine (m-AMSA), etoposide, and teniposide (3).
Studies of 2-Chlorodeoxyadenosine (Cladribine) at St. Jude Children’s Research Hospital

2-Chloro-2′-deoxyadenosine (2-Cd Cladribine) was first synthesized in the early 1970’s but did not undergo wide clinical testing until the last decade. This purine analogue has shown potent oncolytic activity in a variety of adult lymphoid malignancies; in fact, many investigators regarded it as an antilymphocyte drug exclusively [1–3]. Such perceptions grew from observations that lymphocytes contain unusually high concentrations of deoxycytidine kinase, the enzyme primarily (but not solely) responsible for the first step in phosphorylation of 2-CdA, whereas peripheral granulocytes have low concentrations of the kinase. To the contrary, results of in vitro studies indicate that the purine analogue is rapidly phosphorylated by both myeloid cell lines and leukemic blasts from patients with acute myeloid leukemia (AML), and that human cell lines of myeloid origin, as well as human peripheral monocytes, are quite sensitive to this agent [4–6]. 2-CdA is also toxic to cell lines derived from solid tumors, although higher concentrations are needed to produce this effect. We were sufficiently encouraged by these findings to undertake, in 1987, a research program focusing on 2-CdA in pediatric patients. Here we review noteworthy progress in the laboratory and clinical development of this agent and suggest possible applications for the future.
Temporal Rhythms and Patterns of Electronic Documentation in Time-Critical Medical Work

We examine nursing documentation on a newly implemented electronic flowsheet in medical resuscitations to identify the temporal patterns of documentation and how the recorded information supported time-critical teamwork. To determine when the information was documented, we compared timestamps from 58 flowsheet logs to those of verbal communications derived from video review. We also drew on observations of 95 resuscitations to understand the behaviors of nurse documenters. We found that only 8% of the verbal reports were documented in near real-time (one minute within the verbal report), while 42% of reports were not documented in the electronic flowsheet. In addition, 38% were documented early (before the verbal report) and 12% were documented with a delay, ranging from one to 58 minutes after the report. Our study showed that the electronic flowsheet design posed many challenges for real-time documentation, leading to paper-based workarounds and the use of free-text fields on the flowsheet to visualize and keep track of time, and to communicate temporal information to the team. These findings suggest that documenters shape the temporal rhythms of not only their own work but also the rhythms of the electronic record and medical process. We discuss the implications of these rhythms for EHR redesign to support real-time documentation in high-risk, safety-critical settings.
Euthanasia via CO 2 inhalation causes premature cortical granule exocytosis in mouse oocytes and influences in vitro fertilization and embryo development

Generation of high quality mouse metaphase II oocytes is an integral part for efficient in vitro fertilization (IVF), and subsequent embryo production for reproductive studies and genome banking. The main objectives of this study were to investigate the impact of various euthanasia methods on IVF, embryo development, and subcellular structures of MII mouse oocytes. Following superovulation regimen, female mice were euthanized by high flow CO2 (H CO2 ), low flow CO2 (L CO2 ), or cervical dislocation (CD). The MII oocytes obtained from these mice were evaluated for subcellular integrity by assessing their cortical granules and F-actin. Furthermore, fertilization and subsequent embryonic development competence up to blastocyst stage were also evaluated in vitro. The oocytes collected from females euthanized by CD resulted in significantly higher two-cell development rates (p = 0.028) and subsequently lead to in higher embryo development rates (p = 0.027) compared with oocytes from females euthanized by L CO2 . The cortical granule integrity analysis revealed significantly higher rate of premature cortical granules exocytosis (PCGE) for L CO2 group compared with CD and H CO2 groups (p < 0.001). These data collectively suggest that CO2 associated PCGE during euthanasia procedure is the main cause of decreased IVF rates and CD is the optimal euthanasia method for the purpose of obtaining good quality MII oocytes for mouse IVF and other reproductive studies.
Multilevel Optimization Techniques with Application to Trajectory Decomposition

Publisher Summary This chapter discusses some basic principles of decomposition and multilevel optimization as applied to static and dynamic systems, and uses these principles in an entirely new application—the decomposition and multilevel optimization of trajectories. The chapter discusses the concepts of decomposition and second level controllers by examining static systems. A very simple example is used to show the advantages and limitations of the techniques. A new second level controller is derived using the Newton-Raphson algorithm for finding the roots of equations. This controller seemingly can not only be applied to a larger class of problems, but also gives the advantage of calculating the step size for the second level controller algorithm. A new Newton-Raphson controller is derived for dynamic systems, analogous to that for the static systems. Decomposition of a system means to manipulate the system equations in such a manner that they can be uncoupled into smaller subsystems that can be independently optimized.
A Mechanism For Switch Of Integrin Signaling Direction and a New Anti-Thrombotic Strategy Through Selective Outside-In Signaling Inhibition

Antagonists of platelet integrin alphaIIbbeta3 are potent anti-thrombotics due to critical roles of integrins in thrombosis. However, integrins are also important in hemostasis, and thus integrin antagonists have potentially life-threatening bleeding side effect. It would be ideal if we can develop integrin antagonists without bleeding side effect. Integrins transmit signals bidirectionally. Intracellular signals activate integrin alphaIIbbeta3, leading to talin-dependent integrin ligation, which is required for platelet adhesion and initial hemostatic thrombus formation. Integrin ligation in turn mediates Galpha13/Src-dependent outside-in signaling that stabilizes and amplify thrombi, which is crucial for occlusive arterial thrombosis. Here we show that talin and Galpha13 bind to mutually exclusive but distinct sites in integrin beta3, and their bindings are dynamically regulated during integrin signaling. The first talin binding wave mediates inside-out signaling and also “ligand-induced integrin activation”, but is not required for early phase outside-in signaling. Integrin ligation induces talin dissociation and Galpha13 binding, which selectively mediates early phase outside-in signaling. The second talin binding wave is associated with late phase outside-in signaling and clot retraction. Based on these findings, we have designed a selective inhibitor of Galpha13-integrin interaction, which specifically abolished outside-in signaling without affecting inside-out signaling and integrin ligation. Strikingly, this inhibitor potently inhibits occlusive thrombosis in vivo , but has no effect on tail bleeding time, in contrast to the current integrin antagonists. Thus, we have discovered a mechanism for switching the direction of integrin signaling and a new anti-thrombotic that does not cause bleeding. Disclosures: No elevant conflicts of interest to declare.