cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract P5-04-20: Progesterone promotes immunosuppression in breast cancer

Why are some early neoplastic lesions identified through immunosurveillance and subsequently destroyed, whereas other tumors evade this clearance step and progress to clinically-relevant tumors? The cancer immunoediting hypothesis highlights that the innate and adaptive immune responses work together to “flag” early neoplastic lesions for immune-mediated elimination. An early mediator of this “elimination” process is activation of type I interferon signaling. Thus, suppression of type I interferon signaling may help developing tumors evade the critical early steps of immune recognition and clearance. Preliminary data from our lab suggest that progesterone, working through the progesterone receptor (PR), may be a key player in tumor immune evasion through downregulation of interferon signaling. In breast cancer cells, we have shown that presence/activation of PR can attenuate interferon-signaling at multiple steps within the signaling cascade: decreased STAT1 phosphorylation, decreased STAT1/STAT2/IRF9 transcriptional complex formation (called ISGF3, required for interferon-alpha signaling), decreased recruitment of ISGF3 to ISG promoter sequences, and decreased transcriptional activation of interferon-stimulated genes (ISG, end point of interferon signaling). These data suggest a concerted effort aimed at reducing interferon-signaling through activation of PR. These data translate to the immune microenvironment in the murine mammary gland. In mice treated with progesterone for 21 days, we see immunosuppressive changes in the mammary gland: increased T-regulatory cells (immunosuppressive), decreased frequency of antigen-presenting cells (decreased ability to present potential tumor-associated antigens to CD8 T-cells), and a decrease in MHC class I presentation in non-lymphoid cells (decreased ability for epithelial cells to present potential tumor-associated antigens). We observe similar phenotypes in mice with transgenic overexpression of PR. These changes in the immune system suggest that PR can promote immunosuppressive changes in the mammary gland. Moreover, 80% of these mice in a multiparous cohort develop mammary gland tumors. Therefore, early changes in the immune microenvironment in the mammary gland may translate to the development of mammary gland tumors in PR transgenic mice. Cumulatively, these data suggest a mechanism through which PR aids early breast cancer lesions in escaping immune surveillance. These data have significant implications for the use of progesterone-containing hormone replacement therapy, as well as underscore the importance of studying anti-progestins as novel chemo-preventative agents for breast cancer. Citation Format: Christy Hagan, Merit Goodman, Gloria Trinca, Katherine Walter, Katelin Gibson, Prabhakar Chalise, Mary Markiewicz. Progesterone promotes immunosuppression in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-20.
Surgery Resident Time Consumed by the Electronic Health Record.

Objective Time spent on the Electronic Health Record (EHR) influences surgical residents’ clinical availability. Objective data assessing EHR usage among surgical residents are lacking and necessary. Design/Participants Active EHR usage data for 70 surgical residents were collected from April 2015 through April 2016. Active EHR usage was defined as more than 15 keystrokes, or 3 mouse clicks, or 1700 “mouse miles” per minute. Usage data of different specialties, interns (PGY 1), juniors (PGY 2, 3), and seniors (PGY 4, 5) were compared. Setting Carolinas Medical Center, Charlotte, NC. Results Interns spent more time than juniors on total EHR activities per day (134.5 vs 105.5 minutes, p Conclusions These are the first reported objective findings on surgical resident use of the EHR and may provide an opportunity for improvement in EHR training and usage.
Slower World Growth or Global Recession with the Trade War

After the slow recovery from the 2008–2009 global financial crisis, the world economy now faces even slower growth and the prospects of global recession triggered by the USA–China trade war. This paper starts by examining whether the slow growth of the world economy was due to wrong or inadequate economic policies to overcome the crisis (great recession) and return to growth, or for other reasons. Then, it examines the reasons the United States is growing faster than other advanced countries, the slowing growth of emerging market economies (and even economic crisis in some of them), and whether the world is now sliding toward a new global financial crisis and recession triggered by the current trade war.
Unbiased identification of nanoparticle cell uptake mechanism via a genome-wide CRISPR/Cas9 knockout screen

Abstract A major bottleneck in nanocarrier and macromolecule development for therapeutic delivery is our limited understanding of the processes involved in their uptake into target cells. This includes their active interactions with membrane transporters that co-ordinate cellular uptake and processing. Current strategies to elucidate the mechanism of uptake, such as painstaking manipulation of individual effectors with pharmacological inhibitors or specific genetic knockdowns, are limited in scope and biased towards previously studied pathways or the intuition of the investigators. Furthermore, each of these approaches present significant off-target effects, clouding the outcomes. We set out to develop and examine an unbiased whole-genome screening approach using pooled CRISPR/Cas9 libraries for its ability to provide a robust and rapid approach to identify novel effectors of material uptake. Enabling this, we developed a methodology termed fast-library of inserts (FLI)-seq for library preparation and quantitative readout of pooled screens that shows improved technical reproducibility and is easier to perform than existing methods. In this proof-of-concept study we use FLI-seq to identify a solute carrier protein family member, SLC18B1, as a transporter for polymeric micellar nanoparticles, confirming the viability for this approach to yield novel insights into uptake mechanisms.
Predictors of Postoperative Complications After Paramedian Forehead Flaps.

Importance: The predictors of postoperative complications after paramedian forehead flaps (PMFF) are unknown. Objective: To determine whether preoperative factors can predict post-PMFF complication...
Tunability of ammonia adsorption over NaP zeolite

Abstract Porous adsorbents represent an environmentally-friendly and cost-effective alternative for NH3 separation from H2 and N2, particularly in the highly energy intensive Haber-Bosch process. Zeolites are deep-rooted in the world of chemical processes due to their chemical, structural, thermal stabilities, and wide variety of pore architectures. Zeolite NaP with a limiting pore of ~2.9 A, is highly appealing for small molecule separations, in particular for potentially sieving NH3 from N2 and H2. Herein, we demonstrate the modulable and selective ammonia adsorption over nitrogen and hydrogen of Zeolite NaP. The use of different aluminum precursors led to tunable ammonia uptakes. Zeolite morphology, acidity, crystallinity, and textural properties greatly influenced the observed NH3 uptakes. Zeolite NaP synthesized using aluminum isopropoxide, displayed high adsorption selectivities of NH3/H2 = 152, and NH3/N2 = 50. Aluminum hydroxide produced a highly crystalline zeolite NaP sample displaying high NH3 uptake of 8.47 mmol/g 273K. Mesoporosity played an important role on the NH3 uptake over zeolite NaP. A larger pore NaY zeolite was synthesized, and used to validate the ammonia sieving effectiveness of zeolite NaP.
Feedback source modality effects on training outcomes in a serious game

In-game real-time feedback produced significantly higher performance outcomes.Feedback delivered by pedagogical agents resulted in largest retention outcomes.Feedback delivered as audio alone produced negative gains in assessments outcomes.Agent interface modalities did not vary across performance and mental demand scores.Feedback delivered as audio alone resulted in significantly lower mental demand. The aim of this research is to enhance game-based training applications to support educational events in the absence of live instruction. The overarching purpose of the presented study was to explore available tools for integrating intelligent tutoring communications in game-based learning platforms and to examine theory-based techniques for delivering explicit feedback in such environments. The primary tool influencing the design of this research was the open-source Generalized Intelligent Framework for Tutoring (GIFT), a modular domain-independent architecture that provides the tools and methods to author, deliver, and evaluate intelligent tutoring technologies within any instructional domain. Influenced by research surrounding social cognitive theory and cognitive load theory, the resulting experiment tested varying approaches for utilizing an Embodied Pedagogical Agent (EPA) to function as a tutor during interaction in a game-based training environment. Conditions were authored to assess the tradeoffs between embedding an EPA directly in a game, embedding an EPA in GIFT's browser-based Tutor-User Interface (TUI), or using audio prompts alone with no social grounding. The resulting data supported the application of using an EPA embedded in GIFT's TUI to provide explicit feedback during a game-based learning event. Analyses revealed conditions with an EPA situated in the TUI to be as effective as embedding the agent directly in the game environment.
Effect of Tillage and Cover Crop on Corn and Soybean Yields in a Silt Loam Soil

Corn and soybean are among the major crops in the United States. Corn alone covers about 88 million acres, valued at $63 billion of which 20 percent is exported. Adapting corn and soybean production to a changing climate is a critical need as yields are affected by drought and excess water. We studied the effect of tillage, rotation and cover crop on corn (Zea mays L.) and soybean (Glycine max) yields from 2011 to 2013. The study was conducted on a Waldron silty-loam soil at Lincoln University of Missouri's Freeman farm. Twenty four plots of each corn and soybean were established on a 4.05 ha field and arranged in a 3-factor factorial design with 3 replications. The 3 factors (treatments) were tillage at two levels (no-tillage vs conventional tillage), cover crop at two levels (no-rye vs rye) and rotation at four levels (continuous corn, continuous soybean, corn/soybean and soybean/corn rotations). Corn and soybean were planted each year in June and harvested in late October. Rye (Secale cereale) was planted in 12 plots of each corn and soybean immediately after harvest. All corn and soybean plots received 26 kg N, 67 kg P2O5, and 67 kg K2O/ha. However, the corn plots received an additional 202 kg N/ha from urea. Overall, corn yield was significantly affected by year (p=0.001), but not tillage or cover crop. Soybean yield, however, was significantly affected by year (p=0.0001), tillage (p=0.0218) and cover crop (p=0.0531). In addition, on year per year basis, corn yield was significantly affected by tillage in 2011 while soybean yield was significantly affected by tillage and cover crop in 2011 and 2012 (p<0.05). These results suggest that cover crop may have an impact on soybean yield. The study is still being conducted for two more years and will hopefully provide more light on the effects of soil/crop management practices on the yields of corn and soybean in this silt loam soil.
Bioavailability of the green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), in mice: Dose-dependence and improvement via peracetylation

3101 Epigallocatechin-3-gallate (EGCG) has been shown to undergo extensive biotransformation to yield methylated and glucuronidated metabolites in mice, rats, and humans. In the present study, we determined the concentration-dependent uptake of EGCG (20 - 600 μM) by HT-29 human colon cancer cells and the dose-dependence of EGCG plasma and tissue levels following a single dose of EGCG (50 - 2000 mg/kg, i.g. ) to male CF-1 mice. The cytosolic levels of EGCG were linear with respect to extracellular concentration of EGCG following treatment of HT-29 cells for 2 h (915.3 - 6851.6 μg/g). In vivo EGCG exhibited a linear dose-relationship in the plasma (0.03 - 4.17 μg/mL), prostate (0.01 - 0.91 μg/g), and liver (0.09 - 18.3 μg/g). In the small intestine and colon, however, the levels of EGCG plateaued between 500 and 2000 mg/kg, i.g. The levels of 4“- O -methylEGCG and 4’,4”-di- O -methylEGCG parallel those of EGCG with respect to dose. As a means of improving the stability and bioavailability of EGCG, we have also prepared a peracetylated EGCG (AcEGCG) derivative. AcEGCG exhibited enhanced growth inhibitory activity relative to EGCG in both KYSE150 human esophageal squamous cell carcinoma (IC 50 = 10 vs. 20 μM) and HCT116 human colon adenocarcinoma cells (IC 50 = 32 vs. 45 μM). AcEGCG was rapidly converted to EGCG by HCT116 cells, and treatment of cells with AcEGCG resulted in a 2.8 - 30-fold greater intracellular concentration of EGCG as compared to treatment with EGCG. AcEGCG was also more potent than EGCG at inhibiting nitric oxide-production (4.4-fold) and arachidonic acid-release (2.0-fold) from lipopolysaccharide-stimulated RAW264.7 murine macrophages. Intragastric administration of AcEGCG to CF-1 mice resulted in improved bioavailability compared to administration of equimolar doses of EGCG. The plasma AUC 0→∞ of total EGCG was 3.29x10 5 and 1.26x10 5 ((ng/mL) . min) for AcEGCG and EGCG, respectively. The t 1/2 of EGCG was also increased following administration of AcEGCG compared to EGCG (310.4 vs. 135.2 min). The AUC 0→∞ and t 1/2 were also increased in the small intestine (18.5- and 3.3-fold, respectively) and the colon (4.0 and 4.4-fold, respectively). The present study provides information with respect to what concentrations of EGCG are achieveable in mice. Our results suggest that absorption of EGCG from the small intestine is largely via passive diffusion, however, at high concentrations, the small intestinal and colonic tissues become saturated. Acetylation represents a means of increasing the biological potency in vitro , increasing the bioavailability of EGCG in vivo , and may result in improved cancer preventive activity (Supported by NIH grant CA88961) .
Inhibition of in vitro lymphokine synthesis by glucocorticosteroids

At pharmacological levels, glucocorticosteroids inhibited two antigen-induced lymphocyte functions, in vitro proliferation and lymphokine synthesis. Lymphocyte production of both macrophage chemotactic factor (CTX) and macrophage inhibition factor (MIF) were decreased in the presence of hydrocortisone. The corticosteroid also blocked the action of MIF on macrophages but did not interfere with the action of CTX on macrophages. Thus, steroids can suppress the immune response at two different stages: by blocking lymphocyte activation and mediator synthesis and also by interfering with the interaction of certain effector molecules with their target cells. Furthermore, these findings suggested that MIF and CTX have distinct mechanisms of action on the effector macrophages, one being sensitive and one resistant to steroids.
Join on a Cube: Analysis, Simulation, and Implementation

Our recent research effort has been in studying database processing on a cube connected multicomputer system. This paper discusses one part of our work, viz., the study of the join operation. Novel data redistribution operations are employed to improve the performance of the various database operations including join. Though a simple analysis is provided, the data redistribution operations are, in general, difficult to characterize analytically. Thus, a simulation and implementation was carried out to study the performance of these operations and the join operation. Issues involved in the simulation and implementation and a discussion of the results from both are presented in this paper.
Spinal cord stimulator--trial lead migration study.

Objectives. Investigate whether percutaneous spinal cord stimulator (SCS) leads migrate significantly during a 3-day trial, and determine whether the skin anchoring method influences lead migration. Material and Methods. Twenty patients were prospectively enrolled. Ten leads were anchored with suture and tape and 10 were anchored with tape only. A standardized X-ray protocol of lead position was obtained immediately following lead placement and upon completion of the trial. Results. Using a standardized method, SCS leads were measured and movement was calculated. The average movement for leads anchored with tape only was 8.72 mm (SD = 5.77), inferiorly; while movement for leads anchored with suture and tape was 24.49 mm (SD = 11.3), inferiorly. A t -test revealed a significant difference between the groups ( t = 3.9, P = 0.001). Conclusions. Percutaneous SCS trial electrodes migrate significantly, inferiorly, during a 3-day trial. Anchoring the trial electrodes to the skin with a suture and tape results in significantly greater inferior migration when compared with anchoring the lead with tape only.
Tumor Necrosis Factor-α Induces Distinctive NF-κB Signaling within Human Dermal Fibroblasts

The TNF-α receptor-associated factor 2 (TRAF2) and its downstream mediator, the NF-κB-inducing kinase (NIK), have been shown to induce NF-κB activation in 293 cells. Investigating the role these mediators play in human skin, we found that both NIK and TRAF2 failed to evoke transcription from NF-κB-dependent promoters linked to the CAT reporter in human dermal fibroblast cultures, while epidermal keratinocyte cultures demonstrated NIK-dependent signaling. Further, NF-κB activation by TNF-α was unaffected by overexpression of a dominant negative mutant NIK in fibroblasts, despite detection of endogenous TRAF2 and NIK by Western analysis. To explore alternative signaling mechanisms in dermal fibroblasts, we found that the intracellular calcium chelator, 3,4,5-trimethoxybenzoic acid, and the calpain inhibitor,N-acetyl-Leu-Leu-norleucinal, both blocked NF-κB activation; however, the specific proteosome inhibitor, lactacystin, failed to do so. Furthermore, TNF-α receptor mutants lacking a functional death domain failed to stimulate NF-κB, while phosphatidylcholine-phospholipase C inhibition and alkalization of endolysosomal compartments blocked its activation by TNF-α. These data indicate that, while epidermal keratinocytes utilize previously defined, NIK-dependent NF-κB pathways, dermal fibroblasts demonstrate unique NIK/TRAF2-independent signal transduction, where both acidic sphingomyelinase and calpain activity act as surrogate mediators for NF-κB activation.
Allergy-Driven Alternative Splicing of IL-13 Receptor α2 Yields Distinct Membrane and Soluble Forms

IL-13 is a key mediator of allergic inflammation. Its diverse functions are mediated by a complex receptor system including IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. IL-4Ralpha and IL-13Ralpha1 form a high-affinity signaling heterodimer. IL-13Ralpha2 binds IL-13 with high affinity and has been found to exist in membrane and soluble forms. Soluble IL-13Ralpha2 has been postulated as a critical endogenous modulator of IL-13 responses. However, the mechanism of generation for the soluble form remains unclear. We present the initial study that a mechanism for generation of the soluble form is alternative splicing and that alternative splicing yields a distinct form of soluble IL-13Ralpha2. We found that several mouse organs expressed two IL-13Ralpha2 transcripts, the 1152-bp transcript encoding the full-length protein and the 1020-bp transcript lacking exon10, which encodes the transmembrane region. Deletion of exon 10 (DeltaEx10) caused a frameshift resulting in a different amino acid sequence from position 327 to position 339 and early termination. Constructs encoding both splice variants were transfected into WEHI-274.1 cells. Transfectants expressing the full-length transcript had IL-13Ralpha2 on the cell surface but produced minimal soluble IL-13Ralpha2 in the supernatants. In contrast, transfectants expressing the DeltaEx10 transcript displayed no membrane IL-13Ralpha2 but secreted high levels of soluble IL-13Ralpha2 capable of inhibiting IL-13 signaling. Both variants bound IL-13, but the DeltaEx10 variant displayed approximately 2-fold increase in IL-13 binding activity. Expression of the two IL-13Ralpha2 transcripts was differentially regulated in vivo in an experimental allergic asthma model. Thus, alternatively spliced variants of IL-13Ralpha2 may have a distinct biologic function in vivo.
Variational principles for average exit time moments for diffusions in Euclidean space

Let D be a smoothly bounded domain in Euclidean space and let Xt be a diffusion in Euclidean space. For a class of diffusions, we develop variational principles which characterize the average of the moments of the exit time from D of a particle driven by Xt, where the average is taken over all starting points in D.
The Wide-Band Plasma Wave Investigation

As part of the Cluster Wave Experiment Consortium (WEC), the Wide-Band (WBD) Plasma Wave investigation is designed to provide high-resolution measurements of both electric and magnetic fields in selected frequency bands from 25 Hz to 577 kHz. Continuous waveforms are digitised and transmitted in either a 220 kbit s-1 real-time mode or a 73 kbit s-1 recorded mode. The real-time data are received directly by a NASA Deep-Space Network (DSN) receiving station, and the recorded data are stored in the spacecraft solid-state recorder for later playback. In both cases the waveforms are Fourier transformed on the ground to provide high-resolution frequency-time spectrograms. The WBD measurements complement those of the other WEC instruments and also provide a unique new capability for performing very-long-baseline interferometry (VLBI) measurements.
Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is often comorbid with major depressive episodes (MDEs) and both conditions carry a higher rate of suicidal behavior. Hypothalamic–pituitary–adrenal (HPA) axis and serotonin abnormalities are associated with both conditions and suicidal behavior, but their inter-relation is not known. We determined cortisol response to placebo or fenfluramine in MDE, MDE and PTSD (MDE+PTSD), and healthy volunteers (HVs) and examined the relation of cortisol responses to suicidal behavior. A total of 58 medication-free patients with MDE (13 had MDE+PTSD) and 24 HVs were studied. They received placebo on the first day and fenfluramine on the second day. Cortisol levels were drawn before challenge and for 5 h thereafter. The MDE+PTSD group had the lowest plasma cortisol, the MDE group had the highest, and HVs had intermediate levels. There were no group differences in cortisol response to fenfluramine. Suicidal behavior, sex, and childhood history of abuse were not predictors of baseline or postchallenge plasma cortisol. Cortisol levels increased with age. This study finds elevated cortisol levels in MDE and is the first report of lower cortisol levels in MDE+PTSD. The findings underscore the impact of comorbidity of PTSD with MDE and highlight the importance of considering comorbidity in psychobiology.
A new antibody, anti-K12, associated with the Kell blood group system.

. A new antibody, named anti-K12, reacts with a high-frequency red-cell antigen associated with the Kell blood groups. Two examples have been found, both in people having the phenotype K-k+, Kp(a–b +), Js(a–b +). Anti-K12 reacted with all of 1,000 random blood samples, less strongly with some Kp(a + b–) samples, weakly with red cells of the McLeod phenotype and not at all with Ko red cells. It reacted weakly against red cells from children with chronic granulomatous disease with weak Kell antigens. While the data establish a phenotypic association between the K12 antigen and the Kell system, there is no evidence to show whether K12 is an inherited character, and, if so, whether the controlling gene is part of the Kell complex.
Median Masking Technique For The Enhancement Of Digital Images

A nonlinear masking technique has been developed which characterizes digital images by local measures of the median and the median absolute deviation (MAD). Space-variant enhancement is elicited by modifying the local MAD as calculated over a moving window in the original image. The method is found to be effective in edge enhancement and noise cleaning operations.© (1979) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Global nonlinear distributed-parameter model of parametrically excited piezoelectric energy harvesters

A global nonlinear distributed-parameter model for a piezoelectric energy harvester under para- metric excitation is developed. The harvester consists of a unimorph piezoelectric cantilever beam with a tip mass. The derived model accounts for geomet- ric, inertia, piezoelectric, and fluid drag nonlinearities. A reduced-order model is derived by using the Euler- Lagrange principle and Gauss law and implementing a Galerkin discretization. The method of multiple scales is used to obtain analytical expressions for the tip deflection, output voltage, and harvested power near the first principal parametric resonance. The effects of the nonlinear piezoelectric coefficients, the quadratic damping, and the excitation amplitude on the output voltage and harvested electrical power are quantified. The results show that a one-mode approximation in the Galerkin approach is not sufficient to evaluate the per- formance of the harvester. Furthermore, the nonlinear piezoelectric coefficients have an important influence on the harvester's behavior in terms of softening or hardening. Depending on the excitation frequency, it is determined that, for small values of the quadratic damping, there is an overhang associated with a sub- critical pitchfork bifurcation.
Interactions of Cl- and OH radical in aqueous solution

There is a considerable controversy surrounding the nature of the Cl-/OH complex in aqueous solution, which appears as a byproduct of the irradiation of salt solutions in nuclear reactor operation, radioactive waste storage, medicine, and environmental problems. In this work, we report results of combined quantum mechanical molecular mechanics calculations of ground-state free-energy surfaces and absorption spectrum through the CCSDT level of theory that are consistent with the experimental data and suggest that hemibonded HOCl- species may indeed exist in bulk aqueous solution.
Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo

Toll-like receptors (TLRs) and proteinase-activated receptors (PARs) function as innate immune biosensors in mucosal epithelial cells (ECs). We previously reported the functional and physical interactions between TLR4 and PAR(2). We have extended these findings herein by showing the cooperation between PAR(2) and TLR2, TLR3, or TLR4 for activation of nuclear factor-kappaB-dependent signaling in mucosal EC lines. In contrast, activation of PAR(2) negatively regulated TLR3-dependent antiviral pathway, blunting the expression of TLR3/interferon regulatory factor-3 (IRF-3)-driven genes, as well as activation of IRF-3 and STAT1. Consistent with these in vitro observations, PAR(2)(-/-) and TLR4(-/-) mice, which were refractory to footpad edema induced by PAR(2) agonist peptide, were protected from mouse-adapted H1N1 influenza A virus-induced lethality when compared to wild-type (WT) mice. These data support and extend our recently described, novel model of PAR(2)-TLR4 "receptor cooperativity" and highlight the complexity of signaling integration between heterologous innate immune biosensors.
311 EFFECTS OF SERUM DILUTION AND OXIDATION OF ALBUMIN-BOUND BILIRUBIN ON THE DETERMINATION OF THE UNBOUND BILIRUBIN CONCENTRATION BY THE PEROXIDASE METHOD

The peroxidase test, although a sensitive and precise method for determining the unbound bilirubin concentration in serum from jaundiced neonates, has been reported to be inaccurate due to errors from sample dilution as well as oxidation of albumin-bound bilirubin. These potential errors were investigated in serum and defatted albumin solutions. A decrease in the peroxidase-determined apparent unbound bilirubin concentration (AUBC) with increasing serum dilution was found in bilirubin-enriched umbilical cord sera as well as sera from jaundiced infants, but was less marked in bilirubin-enriched defatted albumin solutions. The dilutional decrease in AUBC did not appear to be due to slow oxidation of albumin-bound bilirubin. Instead, the bilirubin-albumin complex was found to have a much lower dissociation rate constant in serum (K-1 ± SD = 3.3 ± 0.2 × 10-3 sec-1) than in defatted albumin solutions (K-1 ± SD = 1.7 ± 0.6 × 10-2 sec-1), causing the dissociation of the complex to be rate-limiting when serum is analyzed at the currently recommended dilution (1:40) and peroxidase concentration (5.0 μg/ml). In addition, there appears to be a dilutional enhancement of bilirubin binding by serum, but not by defatted albumin. Decreasing the serum dilution and peroxidase concentration should significantly improve the accuracy of the peroxidase test. Further studies are needed to clarify the effects of dilution on serum binding of bilirubin.
Oculomotor Nerve Palsy as the Presenting Symptom of Gummatous Neurosyphilis and Human Immunodeficiency Virus Infection: Clinical Response to Treatment

A39-year-oldmanpresentedwith5monthsofworseningrighteyelid ptosis, fatigue, and diplopia, which progressed to include anorexia, low-grade fevers, and arthralgias. An examination revealed a subtlemacular rashonhis trunk,arms,andpalms.Therightpupilwas dilated to 5mmwithout direct or consensual response to light or accommodationwith inferotemporal deviation of the eye. Extraocular movements were impaired in all directions except abduction, with near-complete ptosis of the eyelid. Serumstudies showedapositive rapidplasmareagintestresult (to1:64)andreactivefluorescenttreponemal antibodies and Lyme antibodies. Cerebrospinal fluid analysis demonstratedatotalprotein levelof0.084g/dL(toconvert tograms per liter,multiply by 10.0); a glucose level of 47mg/dL (to convert to millimolesper liter,multiplyby0.055);awhitebloodcellcountof18/μL (to convert to ×109 per liter,multiply by0.001); red blood cell count of 3 × 106/μL (to convert to×1012 per liter,multiply by 1.0); 91% lymphocytes; 9% monocytes; a polymerase chain reaction test result negative for Lymedisease; and aVenereal DiseaseResearch Laboratory test result reactive to 1:2. Subsequent human immunodeficiencyvirus (HIV)antibodyandWesternBlot testswerepositivewith a CD4 lymphocyte count of 307 and a viral load of 30 000. Magnetic resonance imaging of his brain revealed an enlarged enhancing right third cranial nerve in the interpeduncular cistern. A focus of fluid-attenuated inversion recovery hyperintensity and enhancement was also noted in the right temporal lobe cortex (Figure 1). Neurosyphilis was diagnosed, and he was treated with a 2-week course of intravenous penicillin (24 million units daily).
Ceftiofur distribution in plasma and joint fluid following regional limb injection in cattle.

The objective of this study was to evaluate the efficacy of regional intravenous (i.v.) injection of ceftiofur in delivery of this drug to joint fluid and plasma in a limb distal to a tourniquet in five, healthy, adult, mixed breed beef cattle. A tourniquet was positioned in the mid-metacarpal region, and 500 mg of ceftiofur was administered through a catheter in the dorsal common digital vein (DCDV). Plasma samples were collected from the catheter at 15, 30 and 45 min postinjection, and from the abaxial proper palmar vein (APPV) at 15 min postinjection. Synovial fluid was collected from the metacarpal phalangeal joint at 45 min postinjection. Ceftiofur concentrations were estimated in plasma and synovial fluid using high-pressure liquid chromatography (HPLC) and a microbiological assay utilizing Pasteurella haemolytica as the test organism. Both assays indicated highest plasma concentrations of ceftiofur at 15 min, with the concentrations declining with time. Concentrations of ceftiofur in plasma obtained from the DCDV were not significantly different from APPV levels, indicating rapid distribution of ceftiofur within the limb. Microbiological assay always demonstrated higher concentrations of ceftiofur compared with HPLC assay, because the former probably also detected the active metabolites of ceftiofur as well as the parent compound. At 45 min, ceftiofur concentrations determined by HPLC were 251+/-97 and 15+/-5 microg/mL in plasma and synovial fluid, respectively. Regional intravenous injection appears to be a feasible technique to produce rapid distribution of ceftiofur within the limb well above therapeutic concentrations.
The Functional Magnetic Resonance Imaging Data Center (fMRIDC): the challenges and rewards of large-scale databasing of neuroimaging studies.

The Functional Magnetic Resonance Imaging Data Center (fMRIDC) (http://www.fmridc.org) was established in the Autumn of 1999 with the objective of creating a mechanism by which members of the neuroscientific community may more easily share functional neuroimaging data. Examples in other sciences offer proof of the usefulness and benefit that sharing data provides through encouraging growth and development in those fields. By building a publicly accessible repository of raw data from peer-reviewed studies, the Data Center hopes to create a similarly successful environment for the neurosciences. In this article, we discuss the continuum of data-sharing efforts and provide an overview of the scientific and practical difficulties inherent in managing various fMRI data-sharing approaches. Next, we detail the organization, design and foundation of the fMRIDC, ranging from its current capabilities to the issues involved in the submitting and requesting of data. We discuss how a publicly accessible database enables other fields to develop relevant tools that can aid in the growth of understanding of cognitive processes. Information retrieval and meta-analytic techniques can be used to search, sort and categorize study information with a view towards subjecting study data to secondary 'meta-' and 'mega-analyses'. In addition, we detail the technical and policy challenges that have had to be addressed in the formation of the Data Center. Among others, these include: human subject confidentiality issues; ensuring investigator's rights; heterogeneous data description and organization; development of search tools; and data transfer issues. We conclude with comments concerning the future of the fMRIDC effort, its role in promoting the sharing of neuroscientific data, and how this may alter the manner in which studies are published.
Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2

The regulation of mitochondrial quality has emerged as a central issue in neurodegeneration, diabetes, and cancer. We utilized repeated low-dose applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) over 2 weeks to study cellular responses to chronic mitochondrial stress. Chronic MPP+ triggered depletion of functional mitochondria resulting in diminished capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially restored mitochondrial content. In contrast, inhibiting activation of extracellular signal-regulated protein kinases conferred complete cytoprotection with full restoration of mitochondrial functional and morphological parameters, enhancing spare respiratory capacity in MPP+ co-treated cells above that of control cells. Reversal of mitochondrial injury occurred when U0126 was added 1 week after MPP+, implicating enhanced repair mechanisms. Chronic MPP+ caused a >90% decrease in complex I subunits, along with decreases in complex III and IV subunits. Decreases in respiratory complex subunits were reversed by co-treatment with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only partially restored by degradation inhibitors. Chronic MPP+ also suppressed the de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased expression of the mitochondrial transcription factor TFAM. U0126 completely reversed each of these deficits in mitochondrial translation and protein expression. These data indicate a key, limiting role for mitochondrial biogenesis in determining the outcome of injuries associated with elevated mitophagy.
T8 antigen density on peripheral blood lymphocytes remains unchanged during exacerbations of multiple sclerosis

Fluorescence-activated cell sorter (FACS) analysis was used to quantitate the antigen density of the lymphocyte markers T3, T4, T8, and Leu 7 on the surface of peripheral blood mononuclear cells (MNC) from exacerbating/remitting multiple sclerosis (MS) patients. Serial studies showed that the mean fluoresce intensity for all the markers studied did not change significantly during exacerbations. There was a tendency for a generalized decline in T-cells, evidenced by a drop in both T8+- and T4+-cells; however, these changes were not statistically significant. It appears, therefore, that the lymphocyte markers studied here are not useful as markers of disease activity in exacerbating/remitting MS.
Obtaining gas panel metallization patterns by vacuum deposition through rib-supported mask structures

Gas discharge display panel metallization patterns have been obtained directly in a single vacuum deposition step through rib-supported mask structures. This approach provides a simple alternative to screening or photoetching. The rib-supported structures were developed to solve problems of fabricating masks containing long and narrow closely spaced apertures, poorly supported cantilever sections, and free-standing islands. The design of these structures minimizes shadowing from support ribs by using non-line-of-sight deposition techniques. Made out of graphite to avoid chemical attack during cleaning operations and fabricated by air abrasion machining, the self-supported masks are held in intimate mask-to-substrate contact during vacuum deposition by an electrostatic hold-down technique.
Multiplicative Extended Kalman Filter for Relative Rotorcraft Navigation

This paper details the fundamentals of a new approach to navigation for aerial vehicles in confined indoor environments without access to global-position measurements. The approach departs from the common practice of navigating within a globally referenced map, and it instead keeps the position and yaw states relative to the current node in the map. The approach combines elements of graph-based simultaneous localization and mapping with a multiplicative extended Kalman filter. The filter provides accurate state estimates at a fast rate and provides the information necessary for a simultaneous localization and mapping algorithm to maintain a pose graph. Specific details for the relative multiplicative extended Kalman filter are provided. The relative estimation approach is validated with hardware flight tests, and results are compared to motion capture ground truth data. In addition, flight-test results using estimates in the control loop are provided.
Shared-intermediates in the biosynthesis of thio-cofactors: Mechanism and functions of cysteine desulfurases and sulfur acceptors ☆

Abstract Cysteine desulfurases utilize a PLP-dependent mechanism to catalyze the first step of sulfur mobilization in the biosynthesis of sulfur-containing cofactors. Sulfur activation and integration into thiocofactors involve complex mechanisms and intricate biosynthetic schemes. Cysteine desulfurases catalyze sulfur-transfer reactions from l -cysteine to sulfur acceptor molecules participating in the biosynthesis of thio-cofactors, including Fe–S clusters, thionucleosides, thiamin, biotin, and molybdenum cofactor. The proposed mechanism of cysteine desulfurases involves the PLP-dependent cleavage of the C–S bond from l -cysteine via the formation of a persulfide enzyme intermediate, which is considered the hallmark step in sulfur mobilization. The subsequent sulfur transfer reaction varies with the class of cysteine desulfurase and sulfur acceptor. IscS serves as a mecca for sulfur incorporation into a network of intertwined pathways for the biosynthesis of thio-cofactors. The involvement of a single enzyme interacting with multiple acceptors, the recruitment of shared-intermediates partaking roles in multiple pathways, and the participation of Fe–S enzymes denote the interconnectivity of pathways involving sulfur trafficking. In Bacillus subtilis, the occurrence of multiple cysteine desulfurases partnering with dedicated sulfur acceptors partially deconvolutes the routes of sulfur trafficking and assigns specific roles for these enzymes. Understanding the roles of promiscuous vs. dedicated cysteine desulfurases and their partnership with shared-intermediates in the biosynthesis of thio-cofactors will help to map sulfur transfer events across interconnected pathways and to provide insight into the hierarchy of sulfur incorporation into biomolecules. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.
Popliteal entrapment syndrome.A systematic review of the literature and case presentation

Popliteal artery entrapment syndrome (PAES) is rare in young adults. Claudication of the young patient, which is often overlooked, is a very rare symptom for orthopedic surgeons. In elder patients, the physician might expect atherosclerotic claudication, however in young patients, popliteal artery entrapment syndrome (PAES) should be considered as a possibility in the cases of claudication. Here, an unusual presentation of an uncommon disease that is not widely known by orthopedic surgeons is reported.
Genome-wide Analyses of Transcription Factor GATA3-Mediated Gene Regulation in Distinct T Cell Types

The transcription factor GATA3 plays an essential role during T cell development and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene regulation, we identified genome-wide GATA3 binding sites in ten well-defined developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly regulated many critical factors, including Th-POK, Notch1, and T cell receptor subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as well as Th2 cell-nonspecific genes, including several transcription factors. Our data also indicate that GATA3 regulates both active and repressive histone modifications of many target genes at their regulatory elements near GATA3 binding sites. Overall, although GATA3 binding exhibited both shared and cell-specific patterns among various T cell lineages, many genes were either positively or negatively regulated by GATA3 in a cell type-specific manner, suggesting that GATA3-mediated gene regulation depends strongly on cofactors existing in different T cells.
Teaching the tacit knowledge of programming to noviceswith natural language tutoring

For beginning programmers, inadequate problem solving and planning skills are among the most salient of their weaknesses. In this paper, we test the efficacy of natural language tutoring to teach and scaffold acquisition of these skills. We describe ProPL (Pro-PELL), a dialogue-based intelligent tutoring system that elicits goal decompositions and program plans from students in natural language. The system uses a variety of tutoring tactics that leverage students' intuitive understandings of the problem, how it might be solved, and the underlying concepts of programming. We report the results of a small-scale evaluation comparing students who used ProPL with a control group who read the same content. Our primary findings are that students who received tutoring from ProPL seem to have developed an improved ability to solve the composition problem and displayed behaviors that suggest they were able to think at greater levels of abstraction than students in the read-only group.
Larvicidal activity of pectolinaringenin from Clerodendrum phlomidis L. against Culex quinquefasciatus Say and Aedes aegypti L. (Diptera: Culicidae)

Larvicidal activity of 12 fractions and a compound of chloroform extract of Clerodendrum phlomidis L. (Lamiaceae) was assayed for their toxicity against the early fourth-instar larvae of the filarial vector Culex quinquefasciatus Say and dengue vector Aedes aegypti L. The fractions were tested at 100-, 50-, 25- and 12.5-ppm concentrations. The compound pectolinaringenin was tested at 5-, 2.5-, 1.0- and 0.5-ppm concentrations. Among the different fractions, fraction 5 recorded the lowest LC50 and LC90 values of 5.02, 61.63 ppm and 32.86, 73.62 ppm against C. quinquefasciatus and A. aegypti, respectively. The compound pectolinaringenin showed the lowest LC50 and LC90 values of 0.62, 2.87 ppm and 0.79, 5.31 ppm against C. quinquefasciatus and A. aegypti, respectively. This is the first report on the mosquito larvicidal activity of the isolated compound pectolinaringenin from C. phlomidis. The results of this study show that the chloroform extract of C. phlomidis can be used as a potent source and pectolinaringenin as a new natural mosquito larvicidal agent.
Blockage of a "nonspecific" provocational challenge as a model for predicting clinical efficacy.

After using various techniques in a clinical study comparing the efficacy of theophylline with that of a 13-agonist, Joad et al.1 reported that serial histamine challenge offered the greatest correlation with clinical improvement (Fig. 1) and thus was the best method for evaluating duration of action. This provoked debate on the usefulness of a histamine challenge for assessing both older and newer medications or for comparing generic drugs to prototype prescription drugs. Previously, Ahrens et al.2 noted the disparity between the duration of bronchodilation and suppression of airway responsiveness with metaproterenol compared with isoetharine. Both the bronchodilator and airway responsiveness effects were lost with isoetharine by 21/4 hours. However, the airway responsiveness had diminished by half despite maximal bronchodilator effect at 4 hours with metaproterenol. The researchers suggested that methacholine challenges might provide a more relevant means to estimate duration of effect and dosing intervals than the more traditional methods.
Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.
Positive bursts (14- and 6-per second positive spikes) in a patient with a penetrating wound of the brain.

Abstract A case is described of a patient who exhibited positive bursts (14- and 6/sec positive spikes) in waking and sleep EEGs approximately 3.5 months after a penetrating wound to the brain. Pneumoencephalogram revealed the presence of a metallic fragment in the left thalamus which had presumably transversed the cortex, basal ganglia and thalamus on the right side and the third ventricle. Unusual features of this case included the precipitation of the paroxysms by eye closure in waking tracings.