cssi/SciSciGPT-SciSciNet huggingface dataset:
Quinolinone-based agonists of S1P1: Use of a N-scan SAR strategy to optimize in vitro and in vivo activity

We reveal how a N-scan SAR strategy (systematic substitution of each CH group with a N atom) was employed for quinolinone-based S1P(1) agonist 5 to modulate physicochemical properties and optimize in vitro and in vivo activity. The diaza-analog 17 displays improved potency (hS1P(1) RI; 17: EC(50)=0.020 μM, 120% efficacy; 5: EC(50)=0.070 μM, 110% efficacy) and selectivity (hS1P(3) Ca(2+) flux; 17: EC(50) >25 μM; 5: EC(50)=1.5 μM, 92% efficacy), as well as enhanced pharmacokinetics (17: CL=0.15 L/h/kg, V(dss)=5.1L/kg, T(1/2)=24h, %F=110; 5: CL=0.93L/h/kg, V(dss)=11L/kg, T(1/2)=15 h, %F=60) and pharmacodynamics (17: 1.0mg/kg po, 24h PLC POC=-67%; 5: 3mg/kg po, 24h PLC POC=-51%) in rat.
Design of the PRAM network

The Princeton University PRAM computer network provides process to process data transmission rates equivalent to memory access rates with negligible latency penalties and currently costs less than $1000.00 per gigabit/sec. of network bandwidth. The PRAM network architecture described scales to very large computer networks using fast optical technology. The cost of such a PRAM network implementation is expected, in the near term, to fall to $100.00 per gigabit/sec. of network bandwidth. >
Switchable near-zero-index magnetic metamaterial for dynamic beam-scanning lens

A design for a switchable metamaterial is presented that allows for digital control over its bulk properties, from near-zero-index to near-free-space at the targeted operational frequency. A distributed shift register is formed over the slab of metamaterial for individual control of varactor diodes within each unit cell, which tune the resonant frequencies of modified split-ring resonators within selected regions of a hexagonal array. The metamaterial was designed using off-the-shelf components for integration into a cylindrical transformation electromagnetics metamaterial beam-scanning lens for dynamic single-feed antenna beamforming.
On convergence of beliefs in a non-Bayesian model of learning

We study and analyze a non-Bayesian model of learning that was recently proposed by Epstein et al. in [1]. In this model, an agent uses an i.i.d. sequence of observations to update her belief on the true state of the world. The agent receives a series of signals that are generated randomly according to a probability distribution that depends on the true state of the world. The model differs from the standard Bayesian model in that the agent exhibits a bias towards her prior belief. Instead of using Bayes' rule to incorporate new information, the agent takes a convex combination of her prior and the Bayesian update to form the posterior belief. In [1], the authors show that even though in this model the agent underreacts repeatedly to new information, the forecast of the future is asymptotically almost surely correct. In this paper, we prove a much stronger result and show that in the absence of identification problems, the agent will asymptotically almost surely learn the unknown state of the world. We also use a linearization of the update governing evolution of the agent's belief to find the rate of learning and bound it in terms of the Kullback-Leibler divergence of the signal distributions under the true state and other states.
Ciudadanía social y sector informal en América Latina

This article is focused on the intermeshing of the informal sector with the development of social citizenship in Latin America. Since the construction of social citizenship has been strongly influenced by employment, the implications of the latter for the system of stratification and social integration since the end of World War II are discussed, with an analysis of analyzing of their inherent limitations in terms of social exclusion. Finally, in a context of labor market changes and of the minimization of the role of the state, the alternative models of welfare provision that are emerging in the region are assessed.
Constructing fuzzy measures: a new method and its application to cluster analysis

We first prove that for a given set of data there exists a fuzzy measure fitting exactly the data if and only if there exists an exact solution of the associated fuzzy relation equation. Secondly, we continue to study the special neural network we proposed in Proc. IFSA'95 World Congress, pp. 61-64 (1995), and describe a learning algorithm for obtaining an approximate fuzzy measure when no one exactly fits the data. Finally, we propose a clustering method based on fuzzy measures and integrals. A benchmark data set, the well-known Iris data set, is adopted to illustrate the method.
Partisanship and Contested Election Cases in the Senate, 1789–2002

While the Founding Fathers included a number of checks and balances in the U.S. Constitution as a way of dispersing power across the various branches of the federal government, they made no such allowance regarding the internal makeup of Congress. Specifically, Article I, Section 5, Clause 1 of the Constitution states that “Each House shall be the Judge of the Elections, Returns, and Qualifications of its own Members. . . .” This clause, in effect, provides each chamber of Congress with the exclusive authority to determine how its membership will be comprised. Thus, when an election is contested, that is, when a dispute arises regarding who is the rightful occupant of a seat after all votes have been counted and a winner announced, the given chamber operates as the sole arbiter, insulated completely from Executive and Judicial pressures or constraints.
Imre Tóths Phänomenologie des geometrischen Geistes in der voreuklidischen Geometrie

Imre Toth, Querdenker, enfant terrible der Wissenschaftsgeschichte, ist vor knapp drei Jahren verstorben. Er hatte immer wieder Kontroversen entfacht durch originelle und provokante Beitrage, die gegen den allgemeinen Trend und auch gegen den Strich gingen. Besonders bekannt ist er fur seine wissenschaftsgeschichtliche Rekonstruktion des Horizonts der griechischen Geometrie vor Euklid. Das vorliegende Buch, eine Zusammenschau von Betrachtungen zu Spuren nichteuklidischer Geometrie in der Zeit vor Euklid, die im Laufe vieler Jahre entstanden sind, ist posthum erschienen. Es handelt sich um eine Retrospektive, um den Versuch, eine Totale von bereits anderswo vorgelegten Gedanken zu bieten. Das Buch enthalt im Wesentlichen denn auch kaum neue Resultate und nur wenig neue Argumente. Es ist darauf angelegt, als Gesamtbild, durch seine Geschlossenheit, zu uberzeugen. Und es ladt dazu ein, Toths Perspektive und Methode auf der Meta-Ebene zu reflektieren. Mit den Jahren hat sich Toths Position mehr und mehr als dezidierte Implementierung einer Hegelschen Geschichtsauffassung entfaltet. Letztlich ist es auch dies, was sein eigentliches Vermachtnis ausmacht. Man kann das vorliegende Buch als ein exemplarisches Pladoyer fur Toths grundsatzlichen Ansatz zur wissenschaftlichen Geschichtsschreibung lesen. Aus diesem Grund ist es auch uber die antike Mathematikgeschichte hinaus von grosem Interesse – unabhangig davon, ob man sich Toths Schlussfolgerungen im Detail anschliesen mochte. Eine Auseinandersetzung mit TothsMethode und Perspektive ware namlich fur die Wissenschaftsgeschichte ein Gewinn, und N.T.M. 21 (2013) 293–298 0036-6978/13/030293-6 DOI 10.1007/s00048-013-0100-6 Published online: 17 October 2013 2013 SPRINGER BASEL AG
Towards the Bertram-Feinberg-Mukai Conjecture

Abstract In this paper, we prove the existence portion of the Bertram–Feinberg–Mukai Conjecture for an infinite family of new cases using degeneration technique. This not only leads to a substantial improvement of known results but also develops finer tools for analyzing the moduli of rank two limit linear series which should be useful for applications to other higher-rank Brill–Noether problems.
Fine-needle aspiration biopsy findings in patients with small lymphocytic lymphoma transformed to Hodgkin lymphoma

Although small lymphocytic lymphoma (SLL) is an indolent lymphoma, approximately 5% of cases can transform to a higher-grade lymphoma, rarely Hodgkin lymphoma (HL). We report the fine-needle aspiration (FNA) results of 6 cases of SLL/chronic lymphocytic leukemia (CLL) that transformed to HL. FNA findings were correlated with the histologic features and clinical follow-up. The patients included 5 men and 1 woman, ranging in age from 49 to 72 years at the time of SLL/CLL diagnosis with time for development of HL ranging from 0 to 95 months (mean, 49.3 months). The FNA diagnoses were SLL with HL transformation (2 cases), SLL with large atypical cells (1 case), and atypical lymphoid proliferation with large atypical cells (3 cases). Flow cytometry performed in 5 cases (2 FNA specimens) demonstrated a monoclonal B-cell population with CD19/CD5 coexpression. The presence of large atypical mononucleated and binucleated cells in lymph node FNA specimens from patients with SLL/CLL with progressive adenopathy should raise the possibility of transformation to HL. In these cases, histologic confirmation is always recommended, not only to differentiate HL transformation from other entities but also for subclassification of HL.
Acute recovery of oral word production following stroke: patterns of performance as predictors of recovery

Background: Impairments in oral word production are common at the onset of stroke. The identification of factors that predict early recovery has important implications for identifying those at greater risk of continued impaired functioning, and the management of the patient's care following discharge.
Angiotensin as a possible intrarenal hormone in isolated dog kidneys.

The distribution of renal blood flow was measured in isolated blood-perfused dog kidneys using radioactive labeled microspheres. The kidneys were perfused at a constant systolic pressure of 140 mm Hg. For the first 50 minutes of perfusion, flow to the outer zones of the renal cortex was 79±2% (SE) of the total renal blood flow, and inner cortical blood flow accounted for 21±2%. With continued perfusion, inner cortical blood flow increased progressively, reaching 34±3% by 150 minutes--a time when renin substrate was depleted in the perfusates. Infusions of the tetradecapeptide renin substrate (5-50 µg/min) reestablished the fractional distribution of renal blood flow observed in the initial 50 minutes of perfusion, i.e., inner cortical blood flow was reduced significantly from 36±2% to 23±4% (P<0.05). In contrast, infusions of angiotensin II (1-10 µg/min) did not reduce the fractional distribution of renal blood flow to the inner cortex. These data provide evidence to support the hypothesis that angiotensi...
Rapid Plasma-Assisted, Ambient-Pressure Deposition of Conformal Nanocrystalline Zinc Oxide Thin Films for Solar Cell Applications

This paper reports a plasma-assisted, rapid, ambient-pressure, low-temperature one-step process for depositing conformal, non-porous nanocrystalline ZnO thin film on various substrates ranging from Si (100), fused quartz, glass, muscovite, c- and a-plane sapphire (Al 2 O 3 ), to the common polymer polyimide (Kapton TM ). The as-synthesized polycrystalline films range in thickness from 20nm to 200nm, deposited at a growth rate ranging from 2 nm/min to 50 nm/min. The lowest deposition temperature achieved with this method is 180°C and progress is being made in further lowering this temperature. The as-deposited films are highly oriented in the caxis, with (002) being the dominant planes.
Static quantum multiverse

We consider the multiverse in the intrinsically quantum mechanical framework recently proposed in Refs. [1, 2]. By requiring that the principles of quantum mechanics are universally valid and that physical predictions do not depend on the reference frame one chooses to describe the multiverse, we find that the multiverse state must be static—in particular, the multiverse does not have a beginning or end. We argue that, despite its naive appearance, this does not contradict observation, including the fact that we observe that time flows in a definite direction. Selecting the multiverse state is ultimately boiled down to finding normalizable solutions to certain zero-eigenvalue equations, analogous to the case of the hydrogen atom. Unambiguous physical predictions would then follow, according to the rules of quantum mechanics.
ANALYSIS OF HETEROSIGMA CARTERAE1 (CHROMOPHYTA, RAPHIDOPHYCEAE) CHLOROPLAST rpoB GENE SEQUENCE2

The rpoB gene encoding the β-subunit of RNA Polymerase has been isolated from the chloroplast genome of the chromophytic alga Heterosigma carterae (Taylor 1992). The nucleotide sequence contains an open reading frame of 3348 bp, which encodes 1116 amino acids. The H. carterae rpoB gene structure is similar to that of chlorophytic chloroplast rpoB genes with respect to insertion-deletion domains. However, several conserved residues found in all chlorophytic plants and bacterial rpoB genes have not been found in this alga. This is the first nonchlorophytic chloroplast rpoB gene to be analyzed, and our data provide insight concerning regions, and perhaps particular residues, that may be essential to chloroplast RNA polymerase function.
Prediction of Longitudinal Development of Infant Cortical Surface Shape Using a 4D Current-based Learning Framework

Understanding the early dynamics of the highly folded human cerebral cortex is still an actively evolving research field teeming with unanswered questions. Longitudinal neuroimaging analysis and modeling have become the new trend to advance research in this field. However, this is challenged by a limited number of acquisition timepoints and the absence of inter-subject matching between timepoints. In this paper, we propose a novel framework that unprecedentedly solves the problem of predicting the dynamic evolution of infant cortical surface shape solely from a single baseline shape based on a spatiotemporal (4D) current-based learning approach. Specifically, our method learns from longitudinal data both the geometric (vertices positions) and dynamic (temporal evolution trajectories) features of the infant cortical surface, comprising a training stage and a prediction stage. In the training stage, we first use the current-based shape regression model to set up the inter-subject cortical surface correspondences at baseline of all training subjects. We then estimate for each training subject the diffeomorphic temporal evolution trajectories of the cortical surface shape and build an empirical mean spatiotemporal surface atlas. In the prediction stage, given an infant, we first warp all training subjects onto its baseline cortical surface. Second, we select the most appropriate learnt features from training subjects to simultaneously predict the cortical surface shapes at all later timepoints from its baseline cortical surface, based on closeness metrics between this baseline surface and the learnt baseline population average surface atlas. We used the proposed framework to predict the inner cortical surface shape at 3, 6 and 9 months from the cortical shape at birth in 9 healthy infants. Our method predicted with good accuracy the spatiotemporal dynamic change of the highly folded cortex.
Forests and Conservation, 1865–1890

Donald J. Pisani is associate professor of history at Texas AM Donald C. Swain, Federal Conservation Policy, 1921-1933 (Berkeley, 1963); and A. L. Riesch Owen, Conservation under F. D. R. (New York, 1983). See also J. Leonard Bates, "Fulfilling American Democracy: The Conservation Movement, 1907 to 1921," Mississippi Valley Historical Review, 44 (June 1957), 29-57; Gordon B. Dodds, "The Historiography of American Conservation: Past and Prospects," Pacific Northwest Quarterly, 56 (April 1965), 75-81; Gordon B. Dodds, ed., "Conservation and Reclamation in the TransMississippi West: A Critical Bibliography," Arizona and the West, 13 (Summer 1971), 143-71; Thomas LeDuc, "The Historiography of Conservation," Forest History, 9 (Oct. 1965), 23-28; Timothy O'Riordan, "The Third American Conservation Movement: New Implications for Public Policy," Journal of American Studies, 5 (Aug. 1971), 155-71; Donald Fleming, "Roots of the New Conservation Movement," Perspectives in American History, 6 (1972), 5-91; James L. Penick, Jr., "The Resource Revolution," in Technology in Western Civilization, ed. Melvin Kranzberg and Carroll W. Pursell, Jr. (2 vols., New York, 1967), II, 431-48; Robert 0. Beatty, "The Conservation Movement," The Annals of the American Academy of Political and Social Science, 281 (May 1952), 10-19; Grant McConnell, "The Conservation Movement-Past and Present," Western
Form imagery to colors.

The self-reported form imagery of 118 Ss to 4 color primaries was obtained along 5 dimensions, including shape, size, and directionality. All colors evoked nearly every qualitative and quantitative descriptive category of form. Form images were also differentiated by sex and individual differences in ease of imagery These findings regarding color and form perception, not previously reported, were discussed in terms of their methodological implications and future research possibilities.
Irenaeus’ Christology of Mixture

Many studies have been written on Irenaeus' Christology, but almost all focus upon soteriological problems rather than Christology proper. A. Houssiau attempted to rectify this imbalance, providing the best study of Irenaeus' Christology to date, but even he missed the fundamental logic that Irenaeus utilizes to explain the christological union. In this article I contend that Irenaeus uses Stoic mixture theory to conceptualize the christological union, including the relationship between the human and divine in the experiences and activities of Christ. In so saying, I challenge H. A. Wolfson's position that Irenaeus' use of mixture language accords with Aristotelian mixture theory, and I stand against those, including Wolfson and A. Grillmeier, who maintain that Irenaeus' conception of the person of Christ is devoid of philosophical reasoning.
Movements and Homing in Townsend's Mole Near Tillamook, Oregon

Local movements, dispersal, and homing in Townsend's mole, Scapanus townsendii , were studied near Tillamook, Oregon, in 1964. Data on local movements of established, adult moles were obtained from 179 live captures involving 95 moles. Movements were generally restricted throughout the year to isolated tunnel systems or discrete portions of larger systems, suggesting mutually exclusive habits. Mean of the greatest distance between points of capture for 14 individuals of both sexes captured three or more times each was 133 feet. To study juvenile dispersal, 62 nests were excavated and 180 nestlings marked and returned. From 4 to 6 months later, 44 young from 32 nests had moved distances of 43 to 2808 feet from the birthsite. The average distance moved was 572 feet. Some nocturnal, above-ground dispersal was concluded from the study, and constituted most of the annual surface activity of the species. Homing was achieved by moles that were naturally (by flooding) and artificially displaced different distances and across different barriers to movement. Homing activity mostly explained the rapid re-establishment of populations in bottomlands following flooding. Effects of movements and homing on maintenance of populations are discussed.
SketchWorksheets: A Brief Summary

Sketch worksheets are a new kind of sketch-based education software designed to facilitate spatial learning. Each worksheet represents a particular exercise, which the student does on a computer. Students get feedback, based on automatic comparison of their sketch with a hidden solution sketch. A software gradebook, which uses scoring rubrics in the solution sketch, is intended to help instructors in grading. Sketch worksheets have been used in classroom experiments with college students, high school students, and middle-school students. They are domain-independent, requiring only that the exercise involves visual distinctions that the software can understand. They rely on cognitive models of human visual/spatial representations and a model of human analogical matching. An authoring environment enables domain instructors to create new sketch worksheets on their own. CogSketch is freely available for download.
Perspective: research misconduct: the search for a remedy

Research misconduct-fabrication, falsification, and plagiarism-is an insidious problem in the scientific community today with the capacity to harm science, scientists, and the public. Federal agencies require that research trainees complete a course designed to deter such behavior, but the author could find no evidence to suggest that this effort has been effective. In fact, research shows that most cases of misconduct continue to go unreported.The author conducted a detailed examination of 146 individual Office of Research Integrity reports from 1992 to 2003 and determined that these acts of misconduct were the results of individual psychological traits and the circumstances in which the researchers found themselves. Therefore, a course in research misconduct, such as is now federally mandated, should not be expected to have a significant effect. However, a course developed specifically for support staff, who currently do not receive such training, might prove effective.Improving the quality of mentoring is essential to meaningfully deal with this issue. Therefore, the quality of mentorship should be a factor in the evaluation of training grants for funding. In addition, mentors should share responsibility for their trainees' published work. The whistleblower can also play a significant role in this effort. However, the potential whistleblower is deterred by a realistic fear of retaliation. Therefore, institutions must establish policies that acknowledge the whistleblower's contribution to the integrity of science and provide truly effective protection from retaliation. An increase in whistleblowing activity would provide greater, earlier exposure of misconduct and serve as a deterrent.
Analysis on The Function of Different Culture Mediums Influencing Identification of Pathogenic Vibrio

[Objective]To discuss the function of different enrichment broths and culture mediums in identification of parahaemolyticus vibrio and other types of pathogenic vibrio.[Methods]Using mono-vibrio and multi-vibrio as subjects to be tested in the enrichment broths and isolate culture medium which were involved in the 2 versions of The National Standards(Published in 2003 and 2008).[Results]The intensifying effect of alkaline peptone water with 3% sodium chloride was better than sodium chloride crystal-violet enrichment broth.CHROMagar vibrio chromogenic medium had obvious effect in identifying different kinds of vibrio.[Conclusion]The new National Standard has modified the choices of enrichment broths and increases the types of alternative culture medium,which greatly improves the efficiency in testing the parahaemolyticus vibrio and other types of pathogenic vibrio quickly and accurately,and can improve the detection rate of vibrio.
Study on Differentiation and Dedifferentiation of Oryza rufipogon Griff.

The N6Dand NB medium containing different hormones(IAA,NAA,2,4-D,6-BA and KT)were used to study the callus rate of Oryza rufipogon Griff,so as to determine the best medium for O.rufipogon Griff.And the shoot induction rate from embryonic calli was also observed.The result showed that,after the seeds were placed on medium for 7d,the callus ratio from N6Dmedium with 6.0mg/L 2,4-D,3.0mg/L NAA,3.0mg/L IAA,1.5mg/L KT was 56.7%,while the diameter of callus reached to 0.31cm.And then the callus of O.rufipogon Griff were transferred to MS dedifferentiation medium for 24d,the callus became the green plants.This is a quick system for differentiation and dedifferentiation of O.rufipogon Griff.
Water resources crisis forewarning model

According to the characteristics of water resources crises,the cusp catastrophe model was proposed to recognize water resources crisis in years within a given series.A decision table was built using the recognition factors,which were considered the condition attribute,and the recognition result,which was considered the decision attribute.Then,the water resources crisis forewarning indices and forewarning decision rules were obtained by attribute reduction based on the rough set theory.The back-propagation neural network updating model was used to predict the value of the forewarning indices,and we obtained the result by comparing the predictive value with the forewarning decision rules.Based on this,we built the CC-RS-BP model,which is easy to understand and use because it uses rules for forewarning.The CC-RS-BP model provides a new way of forewarning of water resources crisis.
Uprooting the curious grapevine? The transformative potential of reverse standard-setting in the field of human rights

ABSTRACTIn recent years, the top-down nature of human rights norm-setting has been problematized by scholars and practitioners who — inspired by actor-oriented perspectives on human rights — started to explore the potential role of rights users in the further development of human rights norms at the global level. Based on fieldwork with community-based organizations in Guatemala and the Democratic Republic of the Congo, I argue that the empowering potential of this exercise could be amplified by complementing actor-oriented analyses with a sociostructural analysis of how institutionalized power relations shape the potential for reverse standard-setting. Drawing on new empirical material, I propose a more nuanced way to think about reverse standard-setting and identify four issues that require the combination of an actor-oriented analysis and sociostructural analysis: access, influence, avenues for information sharing, and discursive incompatibilities. In doing so, I seek to increase the analytical rigor, ...
Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma

Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS.
¿Y Usted? Social influence effects on consumers' service language preferences

Abstract The phenomenon of consumer multilingualism requires service marketers to consider the impact of service language on service evaluations. While prior research shows that multilingual consumers prefer service in their native language, this research establishes the moderating role of social presence on the relationships between service language and service satisfaction. The current research demonstrates that minority and majority language speakers prefer service in the majority (vs. minority) language when their friend's native language is different from their own. This research also demonstrates the boundary conditions of this effect, including cultural symbolism and self-reward vs. other-directed consumption focus. These findings provide theoretical and managerial implications for service marketing.
The mTOR Pathway Inhibits Expression of the Tumor Suppressors ELF4 and KLF4 Downstream of TCR Signaling to Induce T Cell Proliferation.

Abstract Abstract 3688 Poster Board III-624 Quiescence of circulating naive T cells is maintained by the transcription factors ELF4 and KLF4 downstream of T-cell receptor (TCR) signaling. Hence, loss of ELF4 leads to increased proliferation of CD8+ T cells in response to homeostatic and antigen driven stimuli (Yamada et al, Nature Immunology, 2009). The identification of signals that suppress this restraint of proliferation will aid to enhance immunological memory during vaccination and to better understand development of T-cell acute lymphoblastic leukemias. Consistent with lower threshold of activation by ELF4 deletion in unstimulated naive T cells, we identified a significant downregulation of the dual-specificity phosphatases DUSP1 and DUSP5 in a global gene expression study, which was confirmed at a protein level. Consequently, Elf4−/− CD8 T cells showed sustained phosphorylation of Erk1/2 upon TCR activation. In addition, we found that the PD98059 and LY294002 inhibitors, but not Cyclosporin A, blocked inhibition of ELF4 transcription upon TCR activation independently of CD28 co-stimulation and signals emanating from IL-2R. Furthermore, rapamycin also prevented downregulation of ELF4 transcripts following T cell activation, suggesting that mTORC1 inhibits ELF4 transcription downstream of MAPK and PI3K/Akt pathways. We conclude that the transcription factor ELF4 sets a proliferation threshold in naive T cells by activating DUSPs and that ELF4 suppression upon TCR activation is mediated by mTORC1 downstream of MAPK and PI3K/Akt pathways. Our findings provide important targets of this novel control of T cell proliferation to enhance immune response to vaccination and to prevent expansion of pre-leukemic clones in pediatric patients that fail to respond to current therapies. Disclosures: No relevant conflicts of interest to declare.
Computational analysis of Amsacrine resistance in human topoisomerase II alpha mutants (R487K and E571K) using homology modeling, docking and all-atom molecular dynamics simulation in explicit solvent.

Abstract Amsacrine is an effective topoisomerase II enzyme inhibitor in acute lymphatic leukemia. Previous experimental studies have successfully identified two important mutations (R487K and E571K) conferring 100 and 25 fold resistance to Amsacrine respectively. Although the reduction of the cleavage ligand-DNA-protein ternary complex has been well thought as the major cause of drug resistance, the detailed energetic, structural and dynamic mechanisms remain to be elusive. In this study, we constructed human topoisomerase II alpha (hTop2α) homology model docked with Amsacrine based on crystal structure of human Top2β in complex with etoposide. This wild type complex was used to build the ternary complex with R487K and E571K mutants. Three 500 ns molecular dynamics simulations were performed on complex systems of wild type and two mutants. The detailed energetic, structural and dynamic analysis were performed on the simulation data. Our binding data indicated a significant impairment of Amsacrine binding energy in the two mutants compared with the wild type. The order of weakening (R487K > E571K) was in agreement with the order of experimental drug resistance fold (R489K > E571K). Our binding energy decomposition further indicated that weakening of the ligand-protein interaction rather than the ligand-DNA interaction was the major contributor of the binding energy difference between R487K and E571K. In addition, key residues contributing to the binding energy (ΔG) or the decrease of the binding energy (ΔΔG) were identified through the energy decomposition analysis. The change in ligand binding pose, dynamics of protein, DNA and ligand upon the mutations were thoroughly analyzed and discussed. Deciphering the molecular basis of drug resistance is crucial to overcome drug resistance using rational drug design.
Mixed-Methods Inquiry in Public Administration: The Interaction of Theory, Methodology, and Praxis:

Although the methods wars that were entrenched in most of the social science disciplines well into the 1990s have purportedly ceased, methodological diversity remains rare in public administration....
Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations

Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
Outcomes of salvage autologous stem cell transplantation for multiple myeloma with cytopenias and exposure to novel agents

The treatment of multiple myeloma (MM) has been revolutionized by the introduction of novel therapies. Unfortunately, the vast majority of patients eventually become refractory to these agents and suffer from cytopenias precluding clinical trial participation. The use of a second autologous stem cell transplant (ASCT) as a salvage therapy is a potential option, with median PFS ranging from 6.8 to 18 months and overall survival (OS) ranging from 20 to 55.5 months.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 However, no prior studies have included outcomes of novel agent-refractory patients or evaluated the ability of ASCT to resuscitate hematopoiesis in patients with cytopenias who are typically ineligible for clinical trials.
Online Estimation of Capacity Fade and Power Fade of Lithium-Ion Batteries Based on Input–Output Response Technique

Lithium-ion batteries present promising potential in electrified transportation due to their high-power density and long cycle life. However, during the life cycle, lithium-ion batteries are subject to degrading capacity and power. This paper presents an online estimation approach of capacity fade and analyzes the power fade of lithium-ion batteries using an input–output response method. By processing the waveforms of response, one can predict the actual capacity and internal resistance which characterizes the battery health. In the end, the proposed method is validated experimentally. This provides an online estimation tool to describe the aging effects of batteries. Finally, this analysis suggests an optimal operating depth of discharge considering the battery efficiency.
A closed-form expression for thin lens image irradiance

Computer vision tasks often have the goal of inferring geometric and radiometric information about a 3D environment given limited sensing resources. It is helpful to develop relationships between these real-world properties and the actual measurements that are taken. To this end we propose a new relationship between object radiance and image irradiance based on power conservation and a thin lens imaging model. The relationship has a closed-form solution for in-focus points and can be solved via numerical integration for points that are not focused. It can be thought of as a generalization of Horn's irradiance equation. Through both numerical simulations and comparison with the intensity values of actual images, our equation is shown to provide better accuracy than Horn's equation. Improvement is most notable for near-focused images where the pinhole imaging model implicit in Horn's derivation breaks down. Outside of this regime, our model validates the use of Horn's approximation.
Implementing innovations in global women's, children's, and adolescents' health: Realizing the potential for implementation science

The launch of the United Nations Sustainable Development Goals and the new Secretary General's Global Strategy for Women's, Children's, and Adolescents' Health are a window of opportunity for improving the health and well-being of women, children, and adolescents in the United States and around the
Neutrophil to lymphocyte ratio and outcome in stage III non-small cell lung cancer treated with definitive chemoradiation therapy.

e18512 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to have prognostic value in various types of malignancies. Pretreatment NLR in non small cell lung cancer (NSCLC) has been studied for prognostic value prior to surgical resection (Tomita et al Anticancer Res 2011) as well as prior to initiating platinum based chemotherapy (Yao et al Cancer Immunol Immunother 2013). NLR was assessed as a prognostic indicator for outcome in inoperable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy (CRT). Methods: Retrospective chart analysis was performed on patients with unresectable stage III NSCLC who were treated as part of a phase II protocol (Zhang et al Lung Cancer 2014) with tiw paclitaxel 15 mg/m2 IV followed by timed thoracic radiotherapy (TTR) 6 hours later on Monday/Wednesday/Friday and TTR only on Tuesday/Thursday mornings (total 55Gy). Full dose adjuvant chemotherapy consisted of intravenous carboplatin (AUC 5) on day 1, gemcitabine 1000mg/m2 on...
Cottonseed extraction with a new solvent system: Isohexane and alcohol mixtures

A solvent system, consisting of isohexane and 5 to 25% alcohol, either ethanol (EtOH) or isopropyl alcohol (IPA), was tested for extracting gossypol and oil from cottonseed. The test results indicate that this new solvent system not only is effective in removing free and total gossypol but also is as efficient as n-hexane when extracting oil. The amino acid analysis of cottonseed meal, produced by the new solvent system, is similar to that produced by commercial n-hexane. Present commercial cottonseed extraction and downstream processing of cottonseed oil refining may need little change to adopt this new solvent system. This new solvent system may lead to a solution to the gossypol problem of cottonseed extraction.
Liposome-Entrapped Enzyme Mediated Immunoassays

Liposomes, first described by Bangham, et al.(1965), are membrane vesicles that can form spontaneously by suspending a variety of lipids in water. These vesicles can be prepared as large multilamellar structures containing many internal aqueous compartments or as smaller unilamellar structures with only one internal compartment. If prepared in the presence of marker molecules, such as soluble enzymes, ions or flurophores, the markers are entrapped within the aqueous spaces surrounded by bilayer lipid membranes. In addition, liposome membranes can be labeled with either antigens or antibodies, and they can be lysed by a variety of agents.
In utero detection of T7 phage after systemic administration to pregnant mice

The phage is used as a scaffold to display recombinant libraries of peptides, which provides the means to rescue and amplify peptides that bind target macromolecules. Many reports showed that the T7 phage display method can be used to obtain a ligand-binding peptide for tissue-targeted therapies in adult animals. In utero tissue targeting of fetal tissues may help in the correction of many genetic and metabolic diseases. Here we demonstrate the distribution and detection of T7 phage displaying the C-X7-C peptide library in mouse fetal tissues after systemic injection of T7 phage into pregnant mouse tail vein. T7 phage was recovered from fetal tissues 15 min after injection of T7 phage. Our results suggest that T7 phage may be a useful tool in selecting the tissue-specific ligand-binding peptide for fetal tissues. This approach may be helpful in designing in utero tissue-targeted therapies.
Amino Acid Composition of Malted Cereals and Malt Sprouts1

(1971). Amino Acid Composition of Malted Cereals and Malt Sprouts. Proceedings. Annual meeting - American Society of Brewing Chemists: Vol. 29, Proceedings of the Annual Meeting 1971, pp. 15-21.
Effects of Exposure Time, Season, Substrate Type, and Planktonic Populations on the Taxonomic Composition of Algal Periphyton on Artificial Substrates in the Ohio and Little Miami Rivers, Ohio

Standard glass microscope slides were exposed at the surfaces of the Ohio and Little Miami Rivers at Cincinnati, Ohio, for 1, 2, 4, and 8-week periods in June through November 1966. The maximum cell densities were attained in samples from the Little Miami River after an exposure of 1 or 2 weeks, except in November. In the Ohio River, the maximum counts were observed after exposures of 4 weeks in June and July, and 1 week in August and September. In October and November, the cell density continued to increase with increasing periods of exposure. Distinct successional patterns in the composition of the periphyton populations were not found. The changes in the composition of the periphyton with increased substrate exposure time resulted principally from seasonal changes in environmental conditions and phytoplankton populations. The maximum algal cell density, 29 000/mm 2 , was observed in a 1-week sample collected in the Ohio River. The periphyton populations in both rivers were generally dominated by diatoms, which averaged 68 percent of the cell count. The most important genera were Achnanthes, Cyclotella, Gomphonema, Melosira, Navicula, Nitzschia, Stephauodiscus, and Synedra. Other important groups were the green flagellates and filamentous blue-green, coccoid green, and filamentous green algae. The biomasses on five sets of glass and Plexiglas slides exposed for 2 weeks in the Little Miami River during the period of August through November did not differ significantly.
Design of a GaN-Based, Inductor-less, Wireless Power Transfer System at 40.68 MHz

Wireless power transfer systems have attracted tremendous attention over the past decade. The design of most small size, low power, WPT systems; however, utilizes ferrite to shield and redirect the magnetic fields. This add to the weight and bulk of the system. In this paper, a small and extremely lightweight, PCB based, proof-of-concept WPT system is demonstrated. The circuit operates at 40.68 MHz and is capable of 20 W of output power. It utilizes no discrete inductors other than the WPT coils themselves and weights only 7 grams. The following paper shows the design methodology and the inductor elimination technique used to achieve such design.
Electron Band Structure Studies Using Differential Optical Techniques and High Magnetic Fields

The recent incorporation of differential techniques in optical measurements (1–6) has resulted in an enhancement in sensitivity of two to three orders of magnitude over conventional methods, thereby providing a powerful tool for studying optical properties as well as the band structure of solids. In this technique the crystal under investigation is perturbed by some external force, such as an alternating electric field, stress, or temperature. This perturbation modulates the parameters of the band structure and thereby the complex dielectric constant, which determines both the absorption and the reflection. By synchronously detecting the resulting modulation of the optical properties it is possible to obtain an enhancement over the background of the structure arising from electronic transitions between critical points in the energy bands.
Situated Human–Robot Collaboration: predicting intent from grounded natural language

Research in human teamwork shows that a key element of fluid and fluent interactions is the interpretation of implicit verbal and non-verbal cues in context. This poses an issue to robotic platforms, however, as they have historically worked best when controlled through explicit commands that have employed structured, unequivocal representations of the external world and their human partners. In this work, we present a framework for effectively grounding situated and naturalistic speech to action selection during human-robot collaborative activities. This is accomplished by maintaining and incrementally updating separate “speech” and “context” models that jointly classify a collaborator's utterance. We evaluate the efficacy of the system on a collaborative construction task with an autonomous robot and human participants. We first demonstrate that our system is capable of acquiring and deploying new task representations from limited and naturalistic data sets, and without any prior domain knowledge of language or the task itself. Finally, we show that our system is capable of significantly improving performance on an unfamiliar task after a one-shot exposure.
Influence of Cooling Rate on the Ferrite Prediction Diagram of Duplex Stainless Steel Castings

Six different composition steels were designed based on CD3MWCuN, a common industrial alloy formulated to have a microstructure consisting of 50 pct ferrite and 50 pct austenite. The steels were designed to have ± 10 pct Cr, Ni, and Mo over the nominal composition of CD3MWCuN and were obtained by remelting a keel bar of the base alloy and adjusting the composition. The + compositions variations were achieved simply by adding additional Cr, Ni, or Mo, while the − variations were obtained by adding additional amounts of the remaining major elements to the nominal composition of the keel bar. In this way it was possible to produce a series of alloys where the Cr/Ni equivalent ratio, Creq/Nieq, as calculated using the equations first employed by Schoffler varied from ≈ 1.35 to 1.65. A series of homogenization temperatures ranging from 1000 °C to 1250 °C were used to produce a uniform starting microstructure and the alloys were cooled at rates ranging from 500 °C to 1000 °C/hour from these homogenization temperatures. Air-cooled and water-quenched samples were examined as well. Based on observations of the microstructure a generalized ferrite prediction diagram was developed that takes into account homogenization temperature, cooling rate, and chromium-to-nickel equivalence ratio (Creq/Nieq) to predict the amount of ferrite that can be expected in the alloy. This diagram represents the first major evaluation of ferrite content as a function of homogenization temperature and cooling rate specifically for cast duplex alloys.