cssi/SciSciGPT-SciSciNet huggingface dataset:
CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation

It remains uncertain how the DNA sequence of mammalian genes influences the transcriptional response to extracellular signals. Here, we show that the number of CREB-binding sites (CREs) affects whether the related histone acetyltransferases (HATs) CREB-binding protein (CBP) and p300 are required for endogenous gene transcription. Fibroblasts with both CBP and p300 knocked-out had strongly attenuated histone H4 acetylation at CREB-target genes in response to cyclic-AMP, yet transcription was not uniformly inhibited. Interestingly, dependence on CBP/p300 was often different between reporter plasmids and endogenous genes. Transcription in the absence of CBP/p300 correlated with endogenous genes having more CREs, more bound CREB, and more CRTC2 (a non-HAT coactivator of CREB). Indeed, CRTC2 rescued cAMP-inducible expression for certain genes in CBP/p300 null cells and contributed to the CBP/p300-independent expression of other targets. Thus, endogenous genes with a greater local concentration and diversity of coactivators tend to have more resilient-inducible expression. This model suggests how gene expression patterns could be tuned by altering coactivator availability rather than by changing signal input or transcription factor levels.
Automatic generation of a parallel sorting algorithm

In this paper, we discuss a library generator for parallel sorting routines that examines the input characteristics (and the parameters they affect) to select the best performing algorithm. Our preliminary experimental results show that the automatic generation of a distributed memory parallel sorting routine provides up to a four fold improvement over standard parallel algorithms with typical parameters. With the recent importance of multicore processors, we are extending this work to shared memory. This provides new challenges specific to multicore systems. However, with their increasing popularity, this extension becomes very valuable.
DNA Base Excision Repair Nanosystem Engineering: Model Development

DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity
Diagnostic Utility of Measuring Free Light Chains in the Cerebrospinal Fluid of Patients With Multiple Myeloma

Multiple myeloma involvement of the central nervous system is rare, portends a poor prognosis, and requires rapid clinical intervention. The gold standard for diagnosis is cytology, which is highly insensitive. Abnormal free light chain detection in cerebrospinal fluid was more reliably concordant with clinical diagnosis of central nervous system multiple myeloma than cytology. Free light chain levels in cerebrospinal fluid dynamically correlated with response to therapy. Assessment of free light chains in cerebrospinal fluid can be included in the diagnostic algorithm to diagnose central nervous system multiple myeloma and monitor response to therapy.
THE MECHANISM OF THE STRUCTURAL CHANGES IN SCOLIOSIS

1. The vertebral deformation of structural scoliosis can be explained by an asymmetrical disturbance of epiphyseal growth by pressure. 2. "Vertebral epiphysitis" is a related lesion.
Pre- and postjunctional effects of inflammatory mediators in horse airways.

In addition to their direct contractile effects, histamine (Hist), serotonin [5-hydroxytryptamine (5-HT)], and leukotriene (LT) D(4), in low concentrations, dramatically augment electrical field stimulation (EFS)-induced smooth muscle contractions in equine airways. To determine the mechanism of their action, we studied, in trachealis strips, the effect of these mediators on both cholinergically induced tension and the release of ACh from cholinergic nerves. All three mediators synergistically augmented the contraction of the trachealis that was due to release of endogenous ACh, i.e., EFS-induced contraction. These same mediators caused only a small but parallel shift of the ACh concentration-response curve. Comparison of the mediator effects on the responses to endogenous and exogenous ACh suggested a prejunctional effect. However, release of ACh was augmented only by Hist and 5-HT but not by LTD(4). Hist-induced contraction of trachealis was abolished by pyrilamine (H(1)-receptor antagonist) but not by ranitidine (H(2)-receptor antagonist), whereas thioperamide (H(3)-receptor antagonist) shifted the Hist response curve to the left. The augmenting effect of Hist on EFS-induced contraction was abolished by pyrilamine and unaffected by ranitidine or thioperamide. We conclude that inflammatory mediators can increase endogenous cholinergic responses of equine airways via both prejunctional and postjunctional mechanisms. LTD(4) acts solely on smooth muscle, whereas 5-HT and Hist additionally act on neuronal receptors to facilitate release of ACh. Excitatory effects of Hist, i.e., direct contractile effect, and augmentation of endogenous cholinergic response are both mediated via H(1) receptors, whereas the inhibitory H(3) receptors partially oppose the direct contractile effect of this mediator.
A complex gene superfamily encodes actin in petunia.

Abstract We have shown by several independent criteria that actin is encoded by a very large and complex superfamily of genes in Petunia. Several cDNA and genomic probes encoding actins from diverse organisms (Dictyostelium, Drosophila, chicken and soybean) hybridize to hundreds of restriction fragments in the petunia genome. Actin-hybridizing sequences were isolated from a petunia genomic library at a rate of at least 200 per genome equivalent. Twenty randomly selected actin-hybridizing clones were characterized in more detail. DNA sequence data from four representative and highly divergent clones, PAc2, PAc3, PAc4 and PAc7, demonstrate that these actin-like sequences are related to functional actin genes. Intron positions typical of other known plant actin genes are conserved in these clones. Four of six clones analyzed (PAc1, PAc2, PAc3, PAc4) hybridize to leaf mRNA of the same size (1.7 kb) as that reported for other plant actin mRNAs and to a slightly smaller mRNA species (1.5 kb). Five distinct subfamilies of actin-related genes were characterized which varied in size from a few members to several dozen members. It is clear from our data that other actin gene subfamilies must also exist within the genome. Possible mechanisms of actin gene amplification and genome turnover are discussed.
Impact of Rotor Design on Interior Permanent-Magnet Machines With Concentrated and Distributed Windings for Signal Injection-Based Sensorless Control and Power Conversion

This paper examines the relationship between rotor design, saliency-based signal injection sensorless control, and power conversion properties for four industrially relevant interior permanent-magnet machine configurations: a 36-slot 6-pole stator with v bar rotor, a 36-slot 6-pole stator with flat bar rotor, a 9-slot 6-pole stator with v bar rotor, and a 9-slot 6-pole stator with flat bar rotor. The influence of rotor geometric design variables over the range of current densities at the maximum torque per ampere angle was found using a design of experiments' methodology and standardized regression coefficients. Tradeoffs between sensorless control and power conversion properties are found using a Monte Carlo methodology. Power conversion and sensorless control properties were analyzed using hybrid static and time-stepping finite-element simulations.
Cineradiography Evaluation of the Esophagus in Normal Adults: A Study of 146 Subjects Ranging in Age from 21 to 90 years

Summary In order to afford standards with which the findings in an individual patient can be compared, fluoroscopic and cineradiographic examination of the esophagus was carried out in 146 normal subjects ranging in age from 21 through 90; for each decade 21 to 30 years through 81 to 90 years, 10 to 12 men and 10 to 12 women were studied. Inadequate pharyngeal emptying, manifested by marked vallecular pooling, was present in only 1 subject, an 82-year-old man. The quality of the primary peristaltic wave, the incidence of nonperistaltic contractions, and the mean upright and recumbent esophageal emptying times remained quite constant up to at least the 61 to 70 age period. Within the framework of these over-all trends, there was considerable variation from subject to subject within age groups in the esophageal response to deglutition. In a number of subjects, there was considerable variation in the esophageal response to successive swallows. Fifty-two per cent of the male subjects and 26% of the females exhibited a hiatus hernia upon prone oblique examination without special maneuvers; the difference in sex incidence is statistically highly significant. The incidence of hiatus hernia did not increase with age. Gastroesophageal reflux was demonstrable in slightly less than half of the subjects with hiatus hernia, but in no subject without hernia. A lower esophageal (Schatzki's) ring was demonstrable in 5 subjects (3% of the total number), 4 of whom were male.
Computational study of the mechanism and product yields in the reaction systems C2H3 + CH3 ⇄ C3H6 ⇄ H + C3H5 and C2H3 + CH3 → CH4 + C2H2

The mechanism of the radical−radical reaction C2H3 + CH3 (1) was studied by quantum chemical methods. The pathways of reaction channels observed in previous experimental studies, as well as those of other potential channels, were investigated. The results of the quantum chemical study and of the earlier experimental work were used to create a model of the chemically activated route (C2H3 + CH3 ⇄ C3H6→ H + C3H5) of reaction 1. In this model, energy- and angular momentum-dependent rate constants are calculated using the RRKM method in combination with the microcanonical variational selection of the transition states. Pressure effects are described by solution of the master equation. Temperature and pressure dependences of the rate constants and product yields were investigated. The model was used to predict the rate constants and branching fractions of reaction 1 at temperatures and pressures outside the experimental ranges. The same model was used to analyze kinetics of two other reactions which occur on t...
Design Report for the ½ Scale Air-Cooled RCCS Tests in the Natural convection Shutdown heat removal Test Facility (NSTF)

The Natural convection Shutdown heat removal Test Facility (NSTF) is a large scale thermal hydraulics test facility that has been built at Argonne National Laboratory (ANL). The facility was constructed in order to carry out highly instrumented experiments that can be used to validate the performance of passive safety systems for advanced reactor designs. The facility has principally been designed for testing of Reactor Cavity Cooling System (RCCS) concepts that rely on natural convection cooling for either air or water-based systems. Standing 25-m in height, the facility is able to supply up to 220 kW at 21 kW/m2 to accurately simulate the heat fluxes at the walls of a reactor pressure vessel. A suite of nearly 400 data acquisition channels, including a sophisticated fiber optic system for high density temperature measurements, guides test operations and provides data to support scaling analysis and modeling efforts. Measurements of system mass flow rate, air and surface temperatures, heat flux, humidity, and pressure differentials, among others; are part of this total generated data set. The following report provides an introduction to the top level-objectives of the program related to passively safe decay heat removal, a detailed description of the engineering specifications, design features, andmore » dimensions of the test facility at Argonne. Specifications of the sensors and their placement on the test facility will be provided, along with a complete channel listing of the data acquisition system.« less
Evolutionary adaptation to temperature. VII. Extension of the upper thermal limit of Escherichia coli

What factors influence the ability of populations to adapt to extreme environments that lie outside their current tolerance limits? We investigated this question by exposing experimental populations of the bacterium Escherichia coli to lethally high temperatures. We asked: (1) whether we could obtain thermotolerant mutants with an extended upper thermal limit by this selective screen; (2) whether the propensity to obtain thermotolerant mutants depended on the prior selective history of the progenitor genotypes; and (3) how the fitness properties of these mutants compared to those of their progenitors within the ancestral thermal niche. Specifically, we subjected 15 independent populations founded from each of six progenitors to 44°C; all of the progenitors had upper thermal limits between about 40°C and 42°C. Two of the progenitors were from populations that had previously adapted to 32°C, two were from populations adapted to 37°C, and two were from populations adapted to 41-42°C. All 90 populations were screened for mutants that could survive and grow at 44°C. We obtained three thermotolerant mutants, all derived from progenitors previously adapted to 41-42°C. In an earlier study, we serendipitously found one other thermotolerant mutant derived from a population that had previously adapted to 32°C. Thus, prior selection at an elevated but nonlethal temperature may predispose organisms to evolve more extreme thermotolerance, but this is not an absolute requirement. It is evidently possible to obtain mutants that tolerate more extreme temperatures, so why did they not become prevalent during prior selection at 41-42°C, near the upper limit of the thermal niche? To address this question, we measured the fitness of the thermotolerant mutants at high temperatures just within the ancestral niche. None of the four thermotolerant mutants had an advantage relative to their progenitor even very near the upper limit of the thermal niche; in fact, all of the mutants showed a noticeable loss of fitness around 41°C. Thus, the genetic adaptations that improve competitive fitness at high but nonlethal temperatures are distinct from those that permit tolerance of otherwise lethal temperatures.
Estimation of Ion Impact Energies and Electrode Self-Bias Voltage in Capacitive RF Discharges

The dependences of the electrode self-bias voltage and the ratio of ion energies on electrode area ratio are calculated for a model of capacitively coupled rf discharges. It is assumed that concentric spherical elecrodes with fluid-like radial ion flow adequately models the ion motion, that sheath impedances are dominant, and that ionization processes in the glow are due to ohmically heated electrons. Results show that the ratio of ion energies impacting the smaller electrode to those on the larger depends on the ratio of electrode areas in a more complex manner than a power law.The reason for this is that sheath impedances are more resistive or capacitive at different times in the rf cycle. The self-bias ratio is found to depend relatively little on the ionization model or the pressure but differs substantially from the “power law” result. The agreement of measurements with the model is fairly good.
Community Health Workers: a Resource to Support Antipsychotic Medication Adherence

Community health workers (CHWs) are frontline public health workers who are becoming increasingly integrated into medical settings for the prevention, treatment, and control of chronic disease. In particular, they have demonstrated the ability to improve medication adherence in underserved populations. One overlooked population that could benefit from CHW intervention is individuals with severe mental illnesses such as schizophrenia and bipolar disorder. These conditions are disproportionally weighted to economically disadvantaged communities and people of color, and are typically treated using antipsychotic medications. A number of factors, including social disadvantage, contribute to antipsychotic non-adherence, which is highly prevalent and drastically increases the burden of illness and economic impact of these conditions. This commentary examines the ways in which CHWs may be able to best serve individuals with severe mental illness, and proposes methods for facilitating this expanded scope of work.
Contemporary treatment patterns and outcomes of sarcomatoid bladder cancer.

To characterize the treatment patterns and survival outcomes of sarcomatoid bladder cancer, a rare urothelial variant histology using a large population level cancer database. The National Cancer Database was queried for all cases of sarcomatoid bladder cancer using International Classification of Disease-O-3 morphologic code 8122 between 2004 and 2014. Primary outcome was overall survival. A total of 489 patients met our inclusion criteria and were included in our analysis. Average age at diagnosis was 70.4 years. The majority of the population was male (61.8%) and Caucasian (92.2%). Tumor characteristics included 23.7% cT1, 41.1% cT2 and 15.3% cT3 or above. Median overall survival was 18.4 months (95% CI 13.3–23.6). On multivariate Cox proportional analysis, radical cystectomy alone or with multimodal therapy (chemotherapy or radiotherapy) resulted in a statistically significant reduction in the risk of death as compared to bladder preservation surgery alone. Survival in the radical cystectomy group did not differ between radical cystectomy alone and those receiving either neoadjuvant or adjuvant chemotherapy. Sarcomatoid bladder cancer has poor prognosis with 18.4-month median overall survival. While our data suggest that aggressive treatment improves outcomes, the role of multimodal therapy is unclear. Future study should continue to focus on multi-institutional collaboration to determine the most effective therapy.
In-Store vs. Out-Of-Store Coupons: An Examination of Anglo-, African-, and Hispanic-American Redemption

The consensus among Studies examining differences in coupon redemption between ethnicminority consumers and the general population is that ethnic consumers redeem significantly fewer cents-off coup...
Aesthetic Lip Advancement

Full lips impart a youthful and healthy appearance to the face. When the lips are thin as a result of congenital hypoplasia or the aging process, vermillion border transfiguration is one technique ...
Dose Intensification Using High-Dose Combination Alkylating Agents and Autologous Bone Marrow Support in the Treatment of Primary and Metastatic Breast Cancer: A Review of the Duke Bone Marrow Transplantation Program Experience

In 1989, the treatment for metastatic breast cancer is generally considered palliative Despite the availability of more than 15 active agents in the treatment of this disease and the ability to induce objective tumor regressions in 60%–80% of treated patients, few, if any, patients are cured. Since the 1940s, the median survival for patients with metastatic breast cancer has averaged approximately 22 months, with the median time to treatment failure for most combination chemotherapy regimens studied in randomized clinical trials averaging between 5 and 11 months. Complete responses in the treatment of the disease are infrequent. Most therapeutic regimens, even so-called intensive chemotherapy regimens, rarely produce complete responses in excess of 20%. Several single institution trials more recently have reported complete responses in excess of 30% and may represent important new leads in the treament of this disease [1–3]. Nonetheless, the majority of patients fail to achieve complete disease regression, and relapse and progression of their breast cancer is therefore inevitable.
Comparison of Direct Transfers for Human Capital Development and Environmental Conservation

Summary Over the past 30 years, direct transfers to beneficiaries have become an increasingly important tool for addressing society’s need for effective, efficient, and equitable conservation and development, and have been widely used to generate socially desirable outcomes in human capital development (HCD) programs and Payments for Ecosystem Services (PES) programs. Yet, the two types of programs have been examined in distinct bodies of literature without much reference to each other. By systematically reviewing peer-reviewed journal articles, dissertations, and select working papers, we suggest important similarities and differences between HCD cash transfer and PES programs that have been overlooked, particularly in how direct transfers are conceptualized and operationalized and how intended and unintended program outcomes are produced. Rather than considering HCD cash transfers and PES as two distinct tools, a common framework that conceptualizes direct transfers as an umbrella mechanism to produce socially desirable outcomes can contribute to effectively engaging target populations, addressing the needs of beneficiaries in a holistic way, comprehensively evaluating program impacts, and enabling opportunities to build synergies and minimize redundancies and competition across programs. We conclude by offering five insights into future research, program development, and policy innovations. Specifically, PES programs can learn from HCD cash transfer programs to (1) incorporate considerations of economic and gender inequalities to better sustain long-term environmental outcomes; (2) enhance collaboration among PES scholars, program practitioners, and policy makers to improve PES design and implementation and minimize adverse unintended impacts; (3) use randomized control trials to measure the causal impacts of PES; and (4) reconsider the role of conditionality to promote simultaneous production of environmental, economic, and social benefits. HCD cash transfer programs can learn from PES programs to (5) explore collaborative, community-based program design and implementation to facilitate not only adoption of socially desirable behaviors but also long-term human capital gains.
Data Driven vs. Metric Driven Data Warehouse Design

Although data warehousing theory and technology have been around for well over a decade, they may well be the next hot technologies. How can it be that a technology sleeps for so long and then begins to move rapidly to the foreground? This question can have several answers. Perhaps the technology had not yet caught up to the theory or that computer technology 10 years ago did not have the capacity to delivery what the theory promised. Perhaps the ideas and the products were just ahead of their time. All these answers are true to some extent. But the real answer, I believe, is that data warehousing is in the process of undergoing a radical theoretical and paradigmatic shift, and that shift will reposition data warehousing to meet future demands.
Recall of “The Real Cost” Anti-Smoking Campaign Is Specifically Associated With Endorsement of Campaign-Targeted Beliefs

Though previous research suggests the FDA’s “The Real Cost” anti-smoking campaign has reduced smoking initiation, the theorized pathway of effects (through targeted beliefs) has not been evaluated. This study assesses the relationship between recall of campaign television advertisements and ad-specific anti-smoking beliefs. Respondents in a nationally representative survey of nonsmoking youths age 13–17 (n = 4,831) reported exposure to four The Real Cost advertisements and a fake ad, smoking-relevant beliefs, and nonsmoking intentions. Analyses separately predicted each targeted belief from specific ad recall, adjusting for potential confounders and survey weights. Parallel analyses with non-targeted beliefs showed smaller effects, strengthening claims of campaign effects. Recall of four campaign ads (but not the fake ad) significantly predicted endorsement of the ad-targeted belief (Mean β = .13). Two-sided sign tests indicated stronger ad recall associations with the targeted belief relative to the non-...
Real-time volt/var optimization for distribution systems with photovoltaic integration

This paper presents a two-stage optimization approach to mitigate the rapid voltage fluctuations and minimize the power losses of distribution systems due to the high penetration of photovoltaic (PV) generation. The first stage is a day-ahead optimal strategy which aims to minimize the total voltage deviations and power losses within the constraints of the daily maximum allowable number of operations of the on-load tap changers (OLTCs) and shunt capacitors (SCs). The second stage is a real-time inverter reactive power control to compensate for the uncertainties of PV output and load demand. As a part of the real-time control, an artificial neural network (ANN) approach is used to estimate the system states. In both stages, the optimization problems are formulated as nonlinear optimization problems and solved with direct search algorithms. The real-time optimization method is tested using a Hardware-In-the-Loop (HIL) simulation platform. A modified IEEE 34-node test feeder is applied to demonstrate the effectiveness of the proposed approach.
Periodic Trade in Developing Areas without Markets

Publisher Summary This chapter discusses periodic trade in developing areas without markets and presents a model of itinerant retailing in an underdeveloped region without rural periodic markets. This stage of regional development is important because it sets the background for the future development of complex periodic market systems. Demand rises in a zone far enough from the center such that transport costs deter farmers from making the trip. Beyond this zone, demand can fall below the firm's threshold if the region extends to a hinterland of low enough density of demand and high enough costs of transport. The juggling of household resources by poor people serves to extend the maximum range of goods. The occupational structure of preindustrial towns serves to keep the minimum range of the firm relatively small. Periodic trading is an attempt to convert a monopolistic hold over supply into a concentration of the periodism of demand that is equivalent to the supply firm to an increase in the density of demand.
The FTO Reporter 2010

From the jungles of the Philippines and Colombia to the deserts of Yemen and Somalia, from the mountains of Afghanistan and Pakistan to the cities of the United States and Northern Ireland, 2010 demonstrated that the threat posed by international terrorist organizations is not waning. “Death by a thousand cuts” is what al Qaida in the Arabian Peninsula calls their strategy against America, but the evolving nature of the threat from designated Foreign Terrorist Organizations suggests that the technique is not limited to AQAP. Spanning the ideological spectrum, and claiming a variety of grievances, terrorist organizations pose just as much, if not more, of a danger than they did when the State Department first began designating them in 1997. These are just a few of the conclusions that come out of The FTO Reporter, a collection of selected news stories regarding groups designated by the United States as Foreign Terrorist Organizations (FTO). Even a cursory review of news involving FTOs in 2010 reveals the scope of the problem. And while the FTO Reporter is intended to offer data rather than analysis, themes have emerged. Here, we highlight only a few of those themes focusing on the evolving nature of the terrorist threat. By now it is axiomatic that the threat posed by FTOs is constantly evolving. One need only open a newspaper or tune into the news to see that terrorist groups continue to change their organizational structure, recruitment strategies, and operational tactics. The FTO Reporter, drawing on that open-source intelligence, indicates that 2010 was no different – new terrorist groups were identified while inactive ones were de-listed; terrorist groups expanded their reach and capabilities by increasing FTO cooperation; terror financing continued to pose a challenge to international law enforcement and intelligence officials; and the terrorist groups increasingly turned to the Internet to revolutionize the processes of radicalization, recruitment, training, and planning required for acts of terrorism.
Timolol decreases aqueous humor flow but not Na+ movement from plasma to aqueous.

PURPOSE To determine whether the well-known effect of timolol in reducing ocular pressure and aqueous humor (AH) flow is a function of reduced Na+ movement from plasma to aqueous. Previously, the authors have shown this to be the case for carbonic anhydrase inhibitors. METHODS The rate of appearance of 22Na in rabbit posterior aqueous was measured 1 to 3 minutes after the intravenous injection (time T) of the isotope. One hour before this, the animals received one of the following: two drops of 0.5% timolol, two drops of 3.5% pilocarpine, or 25 mg/kg intravenous methazolamide. At 1 minute (T + 1), a posterior chamber sample was taken; 2 minutes later (T + 3) a second sample was removed from the fellow eye. The rate constant of sodium accession is simply the difference between the two counts/2 minutes. Aqueous flow was measured by dilution of sulfacetamide marker as described previously. RESULTS The rate constant (k(in)) for sodium entering the posterior chamber was 0.036 +/- 0.004 minute-1 (n = 17). Corresponding to previous findings, methazolamide (25 mg/kg intravenous) reduced this to 0.023 +/- 0.003 minute-1 (n = 14). Conversely, timolol (two drops of 0.5% solution) had no effect on kin, which measured 0.037 +/- 0.004 minute-1 (n = 12). Similarly, as expected, pilocarpine had no effect on k(in) (0.035 +/- 0.003 minute-1). Control flow was 3.9 microliters/minute +/- 0.4; after timolol, 2.5 microliters/minute +/-0.1; after methazolamide, 2.4 microliters/minute +/-0.2; after pilocarpine, 3.6 microliters/minute +/- 0.2. These are converted to rate constants by dividing by volume of posterior aqueous (60 microliters). The control rate constant for fluid entry was 0.065 minute-1, 1.8-fold higher than for sodium. CONCLUSIONS A central dogma of the formation of AH (and cerebrospinal fluid) is that fluid moves isotonically from plasma to AH or cerebrospinal fluid and, therefore, that rate constant k(in) for fluid and for sodium are approximately the same. In the authors' hands, the fluid constant was modestly higher than for sodium. This holds for normal function and also for the reduced k(in) for fluid and sodium after carbonic anhydrase inhibition. The k(in) for neither flow nor sodium was affected by pilocarpine. Surprisingly, however timolol, which reduces flow, had no effect on Na+ entry.
Prostaglandin F in reproductive tissues collected during the luteal phase of the estrous cycle and at parturition in Virginia opossums (Didelphis virginiana ).

Prostaglandin F2α (PGF2α) plays a role in the regression of the corpus luteum (CL) in a number of placental mammals. However, the mechanism of luteal regression has not been extensively studied in marsupials. The objectives of this study were to characterize changes in concentrations of PGF2α within utero-ovarian (UO) tissue/venous plasma during the luteal phase of the estrous cycle in Virginia opossums, to correlate these changes with those of plasma progesterone (P4), and to characterize the peripheral pattern of 13,14-dihydro-15-keto-PGF2α (PGFM) in parturient opossums. Ovaries, uteri, UO venous plasma and peripheral plasma were collected on Days 5, 9 and 12 after induced ovulation (n = 3 to 4 opossums/group). In addition, concentrations of PGFM were measured in peripheral plasma collected from two opossums during late gestation (Days 7,9,11 and 12) and at parturition (Day 13). Concentrations of P4, PGFM and PGF2α in tissue homogenates and plasma samples were estimated by radioimmunoassay. In nonpregnant opossums, peripheral P4 levels were highest on Day 5 (38.8 ± 11.1 ng/ml, x ± SEM) declined on Day 9 (22.6 ± 7.4 ng/ml), and were at basal levels by Day 12 (2.4 ± 0.7 ng/ml). Endometrial concentrations of PGF2α increased (P = 0.056) from Day 5 (15.7 ± 4.1 ng/g) to Day 9 (92.1 ± 61.0 ng/g) and were maintained to Day 12 (97.2 ± 25.7 ng/g). Prostaglandin F2α concentrations in UO plasma increased (P < 0.01) from Day 5 (143.1 ± 32.7 pg/ml) to Day 12 (333.0 ± 32.4 pg/ml). Prostaglandin F2α concentrations in ovarian tissue followed a similar pattern and were correlated with UO concentrations (r = 0.708, P < 0.05). In pregnant opossums, the highest levels of peripheral PGFM were recorded in the peripartum period, when luteal regression would also be expected to occur. The negative temporal relationship between peripheral concentrations of P4 and concentrations of PGF2α in UO tissue/venous plasma observed in this preliminary study is consistent with the notion that PGF2α from the ovary and/or uterus may play a role in CL regression in the opossum.
The principle of virtual work, counterfactuals, and the avoidance of physics

Wilson (2017) derives various broad philosophical morals from the scientific role played by the Principle of Virtual Work (PVW). He argues roughly (i) that PVW conditionals cannot be understood in terms of things as large as possible worlds; (ii) that PVW conditionals are peculiar and so cannot be accommodated by general accounts of counterfactuals, thereby reflecting the piecemeal character of scientific practice and standing at odds with the one-size-fits-all approach of “analytic metaphysicians”; and (iii) that PVW counterfactuals are not made true partly by natural laws. I distinguish, elaborate and critically examine various arguments for these morals suggested by the PVW and Wilson’s text, looking especially at what makes a displacement “virtual” and the operation of the conditionals that the PVW takes to express necessary and sufficient conditions for equilibrium. Ultimately, I do not find the PVW to be especially well suited to support Wilson’s morals; some of these arguments fail, whereas others arise from general considerations rather than having to appeal to anything like the PVW.
Anterior Segment Applications of Optical Coherence Tomography Angiography

Purpose: To review the current literature regarding optical coherence tomography angiography (OCT-A) applications in the anterior segment. Methods: A literature search was performed for terms including OCT-Angiography, anterior segment, cornea, conjunctiva, iris, applications and use in ophthalmology. Results: Fifteen studies were identified, 14 in human subjects. Studies with OCT-A of the conjunctiva, episclera, cornea, and iris were identified, some with normal eyes imaged and others with various pathologies. Most of these studies imaged corneal neovascularization. Three studies described protocols used for image acquisition, one of which was referenced by two later papers. Conclusions: OCT-A is a noninvasive technology with recent applications in the anterior segment. Several pilot studies have been performed on various anterior segment structures and disease states however standardization of image acquisition techniques is still needed. Future imaging could allow noninvasive and serial monitoring of pathology as well as recurrence after therapeutic intervention.
Odd and Even-Order Dispersion Cancellation in Quantum Interferometry

Here we introduce a new quantum-optical tool for dispersion management. This technique allows for simultaneous observation of quantum cancellation of odd-order and even-order dispersion using frequency-anticorrelated entangled photons.
Confidence intervals for ratios of linear functions of mixed models with reference to animal breeding data.

Summary Mixed linear models are widely used in animal breeding experiments from which estimates of ratios are desired. This paper presents methods for the development of exact confidence intervals for ratios of linear functions of fixed effects in mixed models. Approximate confidence intervals for ratios involving random effects can also be obtained by these methods. Additional problems considered include pooled ratio estimation from multiple data sets with constant variance and the case of unequal error variance with two sources of heterogeneity. Confidence intervals obtained here are expected to be larger than those based on approximations of the variance of a ratio through Taylor's series, since the latter underestimate the true variance under certain conditions.
The Symbol Linked Explicit Unpacking (SLEU) Method for Solving STEM Problems.

Solving STEM problems requires that data (numbers and units) from a word problem be substituted into a mathematical equation(s) for solution. However, solving STEM problems is an implicit process that provides little or no guidance for the problem solving process. In this study symbols linking the data to the mathematical equation(s) are used to develop an explicit unpacking method for solving STEM problems. This problem solving procedure is termed the SLEU (Symbol Linked Explicit Unpacking) method. The SLEU method provides an explicit stepwise framework to guide students in the solution of STEM problems from the word-problem format of most STEM problems to the mathematical set up and ultimate solution of the problem. Simultaneously, the SLEU method requires students to understand the physicochemical significance of the data in the word problem as it is used in the mathematical equation. The SLEU problem steps can be easily uploaded into software programs for distribution to students for individual, self-guided study.
Epigenetic regulator BMI1 promotes fusion-positive rhabdomyosarcoma proliferation and constitutes a novel therapeutic target

Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma that continues to present significant challenges to pediatric oncology. There are two major subtypes of pediatric rhabdomyosarcoma, alveolar and embryonal. Alveolar rhabdomyosarcomas are characterized by the presence of a PAX-FOXO1 fusion protein and termed fusion-positive (FP-RMS); embryonal rhabdomyosarcomas (ERMS) lack these fusions and are termed fusion-negative (FN-RMS). Fusion-positive rhabdomyosarcoma (FP-RMS) harbors PAX-FOXO1 fusion proteins and has a worse overall outcome compared to FN-RMS, underscoring the critical need to identify novel targets for this disease. While fusion proteins remain challenging therapeutic targets, recent studies have begun to reveal the key intersection of PAX-FOXO1 fusion proteins with the malignant epigenome, suggesting that epigenetic proteins may serve as novel targets in FP-RMS. Here, we investigate the contribution of the epigenetic regulator BMI1 to FP-RMS. We examined RNA-seq tumor datasets and determined that BMI1 is robustly expressed in FP-RMS tumors, patient derived xenografts (PDXs), and cell lines. We depleted BMI1 using RNA interference and find that this leads to a marked decrease in cell growth. Next, we used two BMI1 inhibitors, PTC-209 and PTC-028, and showed that BMI1 inhibition decreases cell cycle progression and increases apoptosis in FP-RMS cell lines. In the in vivo setting, targeting BMI1 leads to decreased tumor growth. Mechanistically, we observe that BMI1 inhibition activates the tumor suppressive Hippo pathway. Collectively, these results identify BMI1 as a novel therapeutic vulnerability in FP-RMS and provide a foundation for further investigation of BMI1 in both FP-RMS and additional sarcoma histotypes.
Abstract WMP26: Aneurysm Location and Its Relationship With Thrombotic and Hemorrhagic Complications During Flow Diversion Procedures: A Meta-Analysis

Background and Purpose: Flow diversion with the Pipeline Embolization Device (PED; Medtronic, Minneapolis, MN) has become increasingly utilized in the treatment of otherwise difficult to manage wid...
Propaganda as Protest Prevention: How Regime Labeling Deters Citizens from Protesting—Without Persuading Them

How do authoritarian regimes prevent protests? One strategy, which frequently accompanies the use of repression, is labeling regime opponents negatively in an attempt to discredit them. This paper considers two frameworks through which negative regime labels about protesters could affect citizens: through persuading them of protesters' illegitimacy, or through signaling the regime's disapproval of protest. We adjudicate the two frameworks with a survey experiment in China which varies regime responses to environmental protest. The results are consistent with the signaling disapproval framework: negative labels do not affect respondents' perceptions of protests but do affect their willingness to protest. Furthermore, these effects depend on respondents' support for the government, and suggest a polarization effect of negative labels. The findings connect research on authoritarian repression and propaganda, suggesting complementarities between the two strategies for regimes.
Uniform large area super-resolved interference lithography via beam scanning

With high contrast optical images, it is possible to write sub-diffraction limited features over large areas. The dimensions of these super-resolved lithographic features are a function of optical contrast and total dose. Writing uniform subwavelength features requires uniform dose, and therefore uniform recording intensity. Patterns written with Gaussian beams exhibit large linewidth variation within each exposure field, and we mitigate this by incorporating a refractive beam shaper. A beam shaper does improve uniformity; however, intensity noise remains an issue. To mitigate intensity noise, we show that it is possible to scan the beam while recording without washing out the interference pattern. This is accomplished with an interferometer that incorporated a diffraction grating as a beam splitter. To first order, this design is insensitive to beam pointing. That is, as pointing angle changes, the interference fringe positions remain fixed while the beam position moves. Scanning over the resist averages out intensity noise, dramatically improving uniformity. We demonstrate both experimentally and with models, linewidth variation across a field written with different recording strategies. Linewidth from a Gaussian recording beam varies by 32% center to beam waist. With the inclusion of refractive beam shaping, linewidth uniformity can be brought down to 13%. By incorporating scanning with beam shaping, linewidth uniformity can be further reduced to as low as 4%.
Response to Letter by Tsuda

Response: Dr Tsuda raised the interesting speculation that production of nitric oxide (NO) might play a role in the neuroprotective effect of leptin against ischemic neuronal injury. Although our study did not address this hypothesis,1 we agree that NO generated via the activation of endothelial nitric oxide synthase (eNOS) could potentially contribute to leptin-mediated neuroprotection in the stroke model. One of the major roles of leptin is to increase energy consumption by augmenting sympathetic outflow,2 which normally …
High-Resolution Design Optimization for IPT Including Stray Field and Coupling Coefficient

Conventional optimization methods for inductive power transfer (IPT) rely on the finite element method (FEM) simulations to extract parameters such as inductances, coupling coefficients, and stray magnetic fields. These simulations are often time-consuming and as a result, a full optimization cannot be achieved. This paper proposes a new design optimization method for IPT systems utilizing a combination of FEM simulations and a feedforward neural network. The proposed method can output a significantly larger number of design points than conventional methods in the same calculation time. Hence, users can select an optimized design point from the plots with higher resolution. This paper presents the proposed design optimization method and compares its benefits and trade-offs to the conventional method. Additionally, a prototype designed by the proposed method is constructed and experimental results are shown to verify the predicted values of inductances, coupling coefficients, and stray magnetic fields for the optimized solution against FEM simulation and the measured results.
Investigating the Link Between Depression, Cognition, and Motivation in Late Childhood.

Research has revealed broad cognitive deficits (e.g., memory, learning) in depression, and that motivation may account for this link. We tested the state (i.e., only present during depression), trait (i.e., underlying vulnerability) and scar (i.e., lasting corollary) hypotheses of cognitive dysfunction in depression. We additionally tested subjective motivation as a mediator of the concurrent depression-cognition link. In a longitudinal sample of 11,878 children ages 9–11, we found no evidence of a concurrent state or longitudinal trait or scar relationship between depression and cognition. The pattern of depression-cognition relationships—which precluded a mediator analysis—in our childhood sample is a departure from previous studies. Our findings indicate that cognitive deficits are not strongly associated with depression in childhood, in contrast with the impairment commonly seen in older individuals with depression.
Direct Antigen Presentation and Chronic Rejection

To the Editor: I read with interest the article by Hornick et al.1 They conclude that direct antigen presentation (donor MHC presented by donor antigen-presenting cells) is an unlikely mechanism to explain the accelerated coronary disease (CAD) that develops after cardiac transplantation. I have concerns regarding these data and conclusions. First and foremost, the data are limited to 10 allograft recipients studied at wide time disparities, with the majority of recipients being at least 4 years past transplantation. Although the development of CAD is progressive, disease occurring later after transplantation is difficult to distinguish from traditional atherosclerosis. Furthermore, most of the alloimmune “action” occurs within the first year after transplantation. Several studies have demonstrated that those patients who develop CAD early have by far the worst prognosis. Only 2 patients were studied in this time frame. Second, only patients with CAD were studied without a control group. The appropriate comparison (assuming consistent time periods) would be those …
The Plight of the "Able Student": Ruth Wright Hayre and the Struggle for Equality in Philadelphia's Black High Schools, 1955-1965.

Within a large city… it would be most unwise to attempt to say what is the correct curriculum or organization of all the high schools under the management of the city school board… I am convinced American secondary education can be made satisfactory without any radical changes in the basic pattern. This can only be done, however, if the citizens in many localities display sufficient interest in their schools and are willing to support them. The improvement must come school by school and be made with due regard for the nature of the community (Dr. James Conant, The American High School Today, 1959). Educational opportunity must be equal for all young people, regardless of the neighborhood they live in and the school they attend (Dr. Ruth Wright Hayre, Principal, William Penn High School for Girls, 1961).
Intrauterine pregnancy following low-dose gonadotropin ovulation induction and direct intraperitoneal insemination for severe cervical stenosis

Background We present a case of primary infertility related to extreme cervical stenosis, a subset of cervical factor infertility which accounts for approximately 5% of all clinical infertility referrals.